Abstracts
S1
Munich, 17th to 19th September 2014
Free Papers
First Munich Conference on Vertigo and Headache in Children and
Adolescents
FP001
The Vestibular System Determines
Lateralization of Cortical Function
The bilateral structure of the central vestibular system consists of
ipsilaterally and contralaterally ascending pathways from the vestibular
nuclei in the brain stem via the thalamus to the multiple multisensory
vestibular areas in the posterior insula and the parietotemporal cortex.
Because vestibular cortex areas are represented in both hemispheres,
they may simultaneously receive unequal vestibular input. There is,
however, only one “global vestibular percept” as two different body
positions or body motions cannot be perceived at the same time. The
vestibular system is the only sensory modality with a hemispheric
dominance, that is, the right hemisphere is dominant in right handers
and the left hemisphere, in left handers.1 This dominance may be the key
to understanding the cortical mechanisms of disorders of “higher
(cognitive) vestibular functions.”2 The localization of handedness and
vestibular dominance in opposite hemispheres is a result of evolution. It
might conceivably indicate that the vestibular system with its hemispheric dominance matures earlier during ontogenesis, subsequently
determining right- or left-handedness.
References
1 Dieterich M, Bense S, Lutz S, et al. Dominance for vestibular cortical
function in the non-dominant hemisphere. Cereb Cortex 2003;13
(9):994–1007
2 Brandt T, Strupp M, Dieterich M. Towards a concept of disorders of
“higher vestibular function”. Front Integr Neurosci 2014;8:47
FP002
Epidemiological Differences in Visual Height
Intolerance between Primary School Children
and Adolescents/Adults
Huppert D.1, Brandt T.1
1
Institute for Clinical Neurosciences and German Center for
Vertigo and Balance Disorders (DSGZ), Ludwig-Maximilians
University of Munich, Munich, Germany
In 2012, the first cross-sectional epidemiological study was conducted
on 3,517 individuals from throughout Germany, aged 14 years and
above, to determine the prevalence, typical symptoms, situations of
occurrence, restrictions, and types of compensational behavior occurring in visual height intolerance (vHI). The lifetime prevalence of vHI
was found to be 28%. It was higher in women (32%) than in men (25%),
and increased with age. Individuals with a family history of vHI or the
accompanying diseases, for example, motion sickness susceptibility,
Menière disease, migraine, or anxiety disorders, also had a higher
prevalence. Initial attacks occurred most often (30%) in the second
decade; however, attacks could manifest throughout life. The main
symptoms of vHI are fearfulness, a queasy-stomach feeling, subjective
postural instability with to-and-fro vertigo, inner agitation, and vegetative symptoms as well as weakness in the knees, palpitations, sudden
sweating, light headedness, and tremor. Climbing a tower is the first and
most common precipitating stimulus followed by hiking, climbing up a
ladder, walking over a bridge, looking out a window or from a balcony on
an upper floor, and climbing up stairs. The range of precipitating height
stimuli broadens over time in more than 50% of afflicted persons. The
most frequent reaction to visual height intolerance is to avoid the
triggering stimuli (> 50%), which may have a considerable impact on
FP003
Dizziness and Vertigo in Adolescents: Actual
Epidemiological Data from Munich
Langhagen T.1,2, Landgraf M.1,2, Gerstl L.2, Albers L.3, von
Kries R.3, Straube A.1,4, Heinen F.1,2, Jahn K.1,4
1
Center for Vertigo and Balance Disorders, Munich
University Hospital, Munich, Germany, 2Department of
Paediatric Neurology and Developmental Medicine, Dr. von
Hauner Children’s Hospital, Munich University Hospital,
Munich, Germany, 3Institute of Social Paediatrics and
Adolescent Medicine, Ludwig-Maximilians-University
Munich, Munich, Germany, 4Department of Neurology,
Munich University Hospital, Munich, Germany
There are very few epidemiological data about dizziness and vertigo in
adolescents. Abu-Arafeh and Russell applied a screening questionnaire
to 2,165 school children (10% of the 5- to 15-year-old children attending
school in Aberdeen, Scotland) of whom 314 reported at least one
episode of vertigo over the last year (18%). In Xian, China, Li et al
investigated 1,567 middle school students and found an overall prevalence of vertigo of 5.6%. We present part of the findings from a
preintervention survey of 1,661 grammar school students of the 8th,
9th, and 10th grade in Munich, Germany. The prevalence of dizziness
and vertigo was 72% of the questioned adolescents. Most adolescents
reported multiple vertigo types. Girls (80%) complained dizziness/
vertigo more often than boys (63%). The most common type of dizziness
was orthostatic dizziness (52% of the students). About 60% of the
students reported duration less than 1 minute, orthostatic dizziness
was from shorter duration than the other vertigo types. About 50% of the
students reported a frequency of more than five times over the past year.
Constraints, as not being able to do leisure activities and not to be able to
get up, were more pronounced for spinning vertigo and swaying vertigo.
Students with any type of vertigo or dizziness reported headache
significant more often than student without headache. Vertigo and
dizziness in adolescents are frequent and often associated with headache. Data as the type of vertigo, the duration, the frequency, and the
associated symptoms are important to get an idea of possible differential
diagnosis, but a clinical examination is needed to make a certain
diagnosis. So, we cannot assure a diagnosis just by questionnaire. The
most common vertigo symptom reported was “getting black before eyes
when getting up rapidly,” which we can attribute to orthostatic dizziness. Spinning and swaying vertigo are less often reported, but are
associated with longer duration and more pronounced constraints. This
correlates with the data of the children and adolescents presenting at a
tertiary center for vertigo. Spinning vertigo (49%) and swaying vertigo
(35%) were the more common vertigo types here and 42% of the
consulting patients also referred to suffer from headache. In 33% of
these consulting patients, the vertigo was attributable to a vestibular
migraine.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Brandt T.1,2, Dieterich M.1,3,4
1
German Center for Vertigo and Balance Disorders, LudwigMaximilians University, Munich, Germany, 2Clinical
Neurosciences, Ludwig-Maximilians University, Munich,
Germany, 3Department of Neurology, Ludwig-Maximilians
University, Munich, Germany, 4Munich Cluster for Systems
Neurology (SyNergy), Ludwig-Maximilians University,
Munich, Germany
daily life and interpersonal interactions, that is, quality of life. The
parameters of vHI are currently being evaluated in an ongoing pilot
study of primary school children between the ages of 8 and 10 years. A
total of 330 children have now been extensively informed about the
symptoms of vHI, and single interviews with 50 affected children have
been conducted. Two important differences from adolescents/adults are
taking shape. vHI of different degrees of severity occurs in approximately 30% of the children. This number is higher than that indicated by
adolescents/adults, 16% (of 28%, i.e., in 4.5% overall) of whom reported in
retrospect that vHI began in childhood. Moreover, there is no clear
gender difference in children, but there is a tendency for vHI to occur
more often in boys. Visual height intolerance is neither seen as a disease,
nor as a shameful attribute. On the basis of the data available so far, one
may assume that the majority of infantile forms of vHI improve with age.
S2
Abstracts
Munich, 17th to 19th September 2014
Vestibular Migraine: New Entity or New Label?
FP004
Dieterich M.1,2,3, Strupp M.1,2
1
German Center for Vertigo and Balance Disorders (DSGZ),
Ludwig-Maximilians-University of Munich, Munich,
Germany, 2Department of Neurology, LudwigMaximilians-University of Munich, Munich, Germany,
3
SyNergy, Munich Cluster for Systems Neurology, Munich,
Germany
Munich, 17th to 19th September 2014
About 50% of the vertigo syndromes in childhood are associated with
migraine.1 The most frequent type of episodic vertigo in adults is
vestibular migraine (VM). Although the clinical characteristics of VM
have been known since 1999 from a study on 90 patients2 and
confirmed in further clinical and epidemiological studies, the longlasting controversy surrounding VM ended just recently in 2013. At that
time, a consensus paper3 of the International Bárány Society and the
International Headache Society finalized the definition of VM that now
appears in the third edition of the International Classification of
Headache Disorders (ICHD-3). Key symptoms are recurrent attacks of
vertigo with various combinations of imbalance of stance and gait,
blurred vision, brain stem signs and nausea, and vomiting associated or
followed by headache (mostly occipital; absent in ! 30%). It is helpful for
the diagnosis to know that approximately 60% of patients with VM show
mild-to-moderate signs of central ocular motor disorders in the symptom-free interval (e.g., gaze-evoked nystagmus, central positional nystagmus, and impaired smooth pursuit). So far, results of prospective
double-blind randomized controlled studies are not available, with the
exception of one on flunarizine,4 which was shown to improve the
frequency, intensity, and duration of vertigo but not the headache
symptoms. Thus, on analogy with migraine without aura, a prophylactic
medication is recommended for frequent attacks, for example, βreceptor blockers such as metoprolol retard, topiramate, valproic acid,
lamotrigine, or flunarizine.
References
1 Jahn K, Langhagen T, Schroeder AS, Heinen F. Vertigo and dizziness in
childhood ‐ update on diagnosis and treatment. Neuropediatrics
2011;42(4):129–134
2 Dieterich M, Brandt T. Episodic vertigo related to migraine (90 cases):
vestibular migraine? J Neurol 1999;246(10):883–892
3 Lempert T, Olesen J, Furman J, et al. Vestibular migraine: diagnostic
criteria: consensus document of the Bárány Society and the International Headache Society [Article in German]. Nervenarzt 2013;84
(4):511–516
4 Lepcha A, Amalanathan S, Augustine AM, Tyagi AK, Balraj A. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol 2013; (Oct):29
FP005
Vestibular Paroxysmia in Children? New
Identity: Established Therapy
Jahn K.1,2, Langhagen T.13,, Lehnen N.1,2, Heinen F.1,3,
Huppert D.1,4, Brandt T.1,4
1
German Center for Vertigo and Balance Disorders, LudwigMaximilians-University of Munich, Germany, 2Department
of Neurology, Ludwig-Maximilians-University of Munich,
Germany, 3Department of Paediatric Neurology and
Developmental Medicine, Ludwig-Maximilians-University
of Munich, Germany, 4Clinical Neuroscience, LudwigMaximilians-University of Munich, Germany
Vestibular paroxysmia (VP) is as frequent cause for short spells of vertigo
in adults. It is diagnosed in 5% of the patient presenting to a tertiary care
dizziness center. The disorder is caused by a pathologic neurovascular
compression of the vestibulocochlear nerve, mostly due to a loop of the
anterior inferior cerebellar artery (AICA). VP has clear diagnostic criteria
and responds excellently to treatment with low-doses of substances that
block use-dependent sodium channels (i.e., carbamazepine). In children,
this disease has been described just anecdotally. In our dizziness clinic
for children, the diagnostic criteria for VP were met in 16 of 400 patients
(4%). The follow-up of three patients (a 12-year-old girl, and two boys, 8
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
and 9 years old) with typical presentation and pathologic neurovascular
compression on magnetic resonance imaging, showed that children—
same as in adults—respond very well to treatment (carbamazepine, 2-4
mg/kg/d). In conclusion, VP has a similar frequency in children and in
adults. In particular, in children between the ages of 8 and 14 years, it is
an important differential diagnosis in patients with short and frequent
vertigo spells. It might be that VP in this age group is favored by the
differential growing of vessels and nerves during early adolescence.
Cerebral Palsy
FP006
Microstructure of Transcallosal Motor Fibers
Reflects Type of Cortical (Re-)Organization in
Congenital Hemiparesis
Juenger H.1, Koerte I.2, Muehlmann M.2, Mayinger M.2,
Krägeloh-Mann I.3, Shenton M.4, Berweck S.5, Mall V.1,
Staudt M.5, Heinen F.6
1
Klinikum Rechts der Isar der TU München, Klinik für
Kinder- und Jugendmedizin, München, Germany, 2Institut
für klinische Radiologie, München, Germany,
3
Universitätskinderklinik Tübingen, Tübingen, Germany,
4
Harvard Medical School, Boston, United States, 5Schön
Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurologische Rehabilitation, Epilepsiezentrum für Kinder
und Jugendliche Vogtareuth, Germany, 6Dr. von
Haunersches Kinderspital, München, Germany
Introduction: Pre- or perinatally acquired unilateral brain lesions can
lead to different types of corticospinal (re-)organization of motor networks. As the primary motor cortex can be (re-)organized in the
contralesional hemisphere, the contralesional hemisphere might exert
motor control not only over the contralateral nonparetic hand but also
over the (ipsilateral) paretic hand. However, some patients with early
unilateral lesions also preserve “normal” contralateral motor projections starting in the lesioned hemisphere. We hypothesized that different patterns of cortical (re-)organization determine interhemispheric
transcallosal connectivity in patients with congenital hemiparesis.
Patients and Methods: In 15 patients with congenital hemiparesis (n
¼ 8 with ipsilateral motor projections [group IPSI] versus n ¼ 7 with
contralateral motor projections [group CONTRA]), magnetic resonance
diffusion tensor imaging (DTI) and volumetric measurements of the
corpus callosum (CC) was performed. The CC was subdivided in five
areas (I-V) in the midsagittal slice. Results: DTI revealed significantly
lower fractional anisotropy (FA), increased trace and radial diffusivity
(RD) for group IPSI compared with group CONTRA in area III of the CC,
where transcallosal motor fibers cross the CC. In area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for
these DTI parameters between the two groups. Volumetric measurements showed lower volume for area II (connecting premotor cortices)
and III in group IPSI. Conclusions: Our results demonstrate that callosal
microstructure reflects the type of cortical (re-)organization in patients
with congenital hemiparesis. We conclude that structural and neuroplastic changes following early unilateral brain lesions are not restricted
to (re-)organization of the M1 and the basal ganglia, but also affect
interhemispheric connectivity, as lesions disrupting corticospinal motor
projections to the paretic hand consecutively affect the development or
maintenance of transcallosal motor fibers.
Abstracts
S3
Munich, 17th to 19th September 2014
FP007
Motor Hand Function Posthemispherotomy: A
Study of 106 Cases
Introduction: Hemispherotomy for refractory epilepsy typically leads to
the loss of contralateral hand function. In children with congenital
hemiparesis, however, the manual grasping function can remain unchanged, indicating that motor reorganization had occurred before the
operation. The aim of this study was to improve the prediction of
individual hand function after hemispherotomy. Patients and
Methods: Retrospective analysis of para-/clinical data of 106 patients
who received a hemispherotomy in our center (40 girls; age at operation
11 months-36 years; median, 5.41 years). Of the 106 patients, 7 patients
had to be excluded due to insufficient documentation or potentially
motor-relevant complications. Results: Overall, 72 patients suffered
from pre-/perinatal lesions (such as focal cortical dysplasias [FCD],
polymicrogyria or infarction of the middle cerebral artery); 24 patients
from postneonatally acquired/progressive diseases (such as traumatic
brain injury, Rasmussen encephalitis); classification was not possible in
three cases. Of the 99 patients, 22 could grasp with their contralateral
hand after hemispherotomy. Of these, 19 of 24 could already grasp
preoperatively and 5 of 24 patients acquired this ability only after the
operation (age at operation 2-13 years). Of the 99 patients, 23 of 24 of
those children who could grasp postoperatively had a pre-/perinatal
lesion. Of the 75 patients without postoperative grasping function, 46
children could also not grasp preoperatively. Overall, 29 children lost
their grasping ability with the operation, among these all 3 with
preoperative normal hand function and 6 of 12 of the patients with
FCD (5/12 of the children with FCD could also not grasp preoperatively).
When preoperative transcranial magnetic stimulation (TMS) indicated
corticospinal projections to the paretic hand exclusively from the
contralesional hemisphere, a postoperative preservation of a preoperative grasping function could be predicted (10/11 cases). Discussion:
Many children with a preoperative grasp function do not lose this ability
in the course of a hemispherotomy (19/48); some children who cannot
grasp preoperatively only develop this ability postoperatively (5/51).
Detection of exclusively ipsilateral projections to the paretic hand by
TMS seems to be predictive for preservation of the grasping function
postoperatively (10/11 children). Predictive for a complete loss of a
preoperatively existent hand function is (1) a preoperatively normal
hand function (3/3), (2) a postneonatally acquired lesion (7/7), and (3)
an FCD as etiology for the epilepsy (6/7 children with FCD and preoperatively existent grasping function). The phenomenon of postoperative
development of manual grasping function is probably based on an
epileptic functional disturbance of the hand function, whose postoperative cessation only enables an efficient ipsilateral control. A prediction
of this phenomenon remains difficult.
FP008
Mirror Movements in Congenital Hemiparesis:
Specific Impact on Bimanual Activities of Daily
Living
Adler C.1, Becher T.2, Hägele A.2, Berweck S.1, Staudt M.1
1
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurologische Rehabilitation, Epilepsiezentrum für Kinder
und Jugendliche, Vogtareuth, Germany, 2Sana Kliniken
Düsseldorf GmbH, Kinderneurologisches Zentrum,
Düsseldorf, Germany
Introduction: Many children with congenital hemiparesis show mirror
movements (MM): involuntary associated movements of the other hand
FP009
Effect of Deep Brain Stimulation of the Internal
Globus Pallidus on Quality of Life in Pediatric
Patients with Dystonic-Dyskinetic Cerebral
Palsy
Koy A.1, Visser-Vandewalle V.2, Fricke O.3, Pauls K.1, Bäumer
T.4, Berweck S.5, Bevot A.6, Deuschl G.7, Häußler M.8, Heinen
F.9, Korinthenberg R.10, Krauss J.11, Kühn A.12, PrinzLangenohl R.13, Schröder A.14, Voges J.15, Schnitzler A.16,
Timmermann L.1
1
Universitätsklinik Köln, Klinik und Poliklinik für
Neurologie, Köln, Germany, 2Universitätsklinik Köln, Klinik
für Stereotaktische und Funktionelle Neurochirurgie, Köln,
Germany, 3Universitätsklinik Köln, Klinik und Poliklinik für
Kinder- und Jugendmedizin, Köln, Germany,
4
Universitätsklinikum Schleswig-Holstein, Campus Lübeck,
Klinik für Neurologie, Lübeck, Germany, 5Schön Klinik
Vogtareuth, Neuropädiatrie, Vogtareuth, Germany,
6
Universitätsklinik Tübingen, Universitätsklinik für Kinderund Jugendmedizin, Tübingen, Germany,
7
Universitätsklinikum Schleswig-Holstein Campus Kiel,
Klinik für Neurologie, Kiel, Germany, 8Universitätsklinikum
Würzburg, Kinderklinik und Poliklinik, Würzburg,
Germany, 9Klinikum der Universität München Campus
Innenstadt, Kinderklinik und Kinderpoliklinik im Dr. von
Haunerschen Kinderspital, München, Germany,
10
Universitätsklinikum Freiburg, Klinik für Allgemeine
Kinder- und Jugendmedizin, Freiburg, Germany, 11Kliniken
der Medizinischen Hochschule Hannover, Klinik für
Neurochirurgie, Hannover, Germany, 12Charité ‐
Universitätsmedizin Berlin, Klinik für Neurologie, Berlin,
Germany, 13Universität Köln, Zentrum für Klinische Studien
Köln, Köln, Germany, 14Klinikum der Universität München
Campus Innenstadt, Kinderklinik und Kinderpoliklinik im
Dr. von Haunerschen Kinderspital, München, Germany,
15
Universitätsklinik Magdeburg, Universitätsklinik für
Stereotaktische Neurochirurgie, Magdeburg, Germany,
16
Universitätsklinikum Düsseldorf, Neurologische Klinik,
Düsseldorf, Germany
Objective: This article aims to evaluate the effect of bilateral deep brain
stimulation (DBS) of the internal globus pallidus on quality of life, but
also on dystonia, spasticity, dyskinesia, motor function, speech, pain
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Küpper H.1, Pieper T.2, Kudernatsch M.3, Groeschel S.1,
Winkler P.2, Holthausen H.2, Berweck S.2, Kolodziejczyk D.3,
Staudt M.1,2
1
Universitätsklinik für Kinder- und Jugendmedizin
Tübingen, Abteilung III: Neuropädiatrie,
Entwicklungsneurologie und Sozialpädiatrie, Tübingen,
Germany, 2Schön Klinik Vogtareuth, Klinik für
Neuropädiatrie, Neurologische Rehabilitation,
Epilepsiezentrum für Kinder und Jugendliche, Vogtareuth,
Germany, 3Schön Klinik Vogtareuth, Klinik für
Neurochirurgie und Epilepsiechirurgie, Vogtareuth,
Germany
during intended unimanual movements of one hand. We investigated in
how far this phenomenon negatively influences the performance of
bimanual activities of daily living (ADL), irrespective of the level of
unimanual impairment. Patients and Methods: We examined 18
children with congenital hemiparesis, 9 with mirror movements (MM
+; age, 6.2-15.5 years) and 9 without mirror movements (MM#; age, 9.916.7 years). The two groups showed a comparable unimanual capacity
(Jebson Taylor Hand Function Test [JTHFT]) MM+: 170-633 seconds;
median, 428 second JTHFT MM#: 122-720 seconds; median, 413
seconds; p ¼ 0.466]. We assessed bimanual performance using the
Assisting Hand Assessment (AHA) as well as the performance of five
bimanual ADLs (untwist a bottle, open a package of potato chips, unpack
a chocolate bar, unpack a piece of candy, and poke a straw into a juice
box) we had identified in a prestudy as particularly difficult for patients
with MM. Results: As expected, for the whole group, unimanual
capacity (JTTHF) correlated with bimanual performance (AHA; Spearman; p ¼ 0.005) and with the overall time needed to perform the five
bimanual ADLs (Spearman; p ¼ 0.068). The group of children with
mirror movements, however, showed a significantly worse bimanual
performance (AHA [MM+]: 30-66 units; median, 49; AHA [MM#]: 35-68
units; median, 58; p ¼ 0.049) and performed the bimanual ADLs slower
(MM+: 169-540 seconds; median, 364 seconds; MM#: 54-391 seconds;
median, 198.4 seconds; p ¼ 0.010) than the group of children without
mirror movements. Discussion: Irrespective of the level of unimanual
impairment, mirror movements have a specific negative impact on the
performance of bimanual ADLs in children with congenital hemiparesis.
Therapeutic approaches to treat children with congenital hemiparesis
should therefore consider this phenomenon.
S4
Abstracts
Munich, 17th to 19th September 2014
Munich, 17th to 19th September 2014
perception, mood, and cognitive function in pediatric patients with
dyskinetic cerebral palsy (CP). Background: CP is the most common
cause for secondary dystonia. Pharmacological treatment is often
unsatisfactory and side effects are frequently dose limiting. Data on
the outcome of DBS in pediatric patients with dyskinetic CP remain
scarce. A meta-analysis on the percentage change in dystonia severity
assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) in
patients with secondary dystonia revealed an improvement of 23.6%.1
Some of the CP patients seem to improve subjectively on pallidal
stimulation but without measurable changes in formal testing for
dystonia.1 Methods: STIM-CP is designed as a prospective, multicenter,
single-arm trial (pre-post design) with a randomized double-blind
crossover phase at the end of the trial and is monitored by the Clinical
Trials Center of Cologne (EK-13-359; DRKS00005797; ClinTrial.gov
NCT02097693). A total of 11 German DBS centers are participating,
20 patients with dyskinetic CP (age 7-18 years) receiving bilateral DBS of
the globus pallidus internus (GPi) will be included. The CPCHILD
questionnaire (Available at http://www.sickkids.ca/Research/CPCHILDQuestionaire/CPCHILD-Project/index.html) will be the primary outcome parameter 12 months after DBS surgery. Secondary outcome
parameters include severity of dystonia, spasticity and dyskinesia,
motor function, speech, pain perception, mood, attention and cognitive
function, and will be assessed 6 and 12 months, postoperatively. After
the last assessment, patients will be scored in a randomized doubleblind crossover setting with stimulation ON or OFF for up to 24 hours.
Videos will be taken before DBS surgery, 12 months after and before
changing the stimulation parameters during the crossover setting. The
BFMDRS and the Dyskinesia Impairment Scale will be assessed by
blinded raters. Discussion: To date, there is only limited data about
the effect of GPi-DBS on quality of life, especially in pediatric CP patients.
Only a comprehensive assessment with the focus on quality of life and
function in daily activities in a well-described cohort of young CP
patients could help to quantify the overall effect of DBS in these patients
more thoroughly. This could contribute to the counseling of affected
patients and their families in the future—especially in light of the
unsatisfactory medical treatment options.
Reference
1 Koy A, Hellmich M, Pauls KA, et al. Effects of deep brain stimulation in
dyskinetic cerebral palsy: a meta-analysis. Mov Disord 2013;28
(5):647–654
FP010
Comparison of Automatic Computer-Based
General Movement (GM)-Analysis and Clinical
GM-Analysis
Philippi H.1, Karch D.2, Kang K.3, Wochner K.3, Dickhaus H.2,
Pietz J.3, Hadders-Algra M.4
1
SPZ Frankfurt Mitte ‐ Epilepsieambulanz, Frankfurt am
Main, Germany, 2Institut für Biometrie und Informatik,
Heidelberg, Germany, 3Zentrum f. Kinder- u. Jugendmedizin
Heidelberg, Neuropädiatrie/Sozialpädiatrisches Zentrum,
Heidelberg, Germany, 4Medizinisches Zentrum UMCG ‐
Entwicklungsneurologie, Groningen, Niederlande
Introduction/Aim: Among many neurological examination techniques
general movements (GM) analysis has turned out to be a good method
for the neurological evaluation of 3 months old infants. However, valid
pattern recognition of GMs in infants is rather ambitious and requires
intensive training. Therefore, automatic computer-based analysis of
GMs could be a great assist. With a novel computer-based approach
using a magnet tracking system, we were able to identify representative
movement patterns, representative of clinical GM analysis. Methods: At
the age of 3 months, corrected age GMs were analyzed in high- and lowrisk infants both by means of clinical “Gestalt” videos analysis and
automatic kinematic analysis using the magnetic tracking system. The
results were compared with neurodevelopmental outcome at the age of
2 years. Results: A total of 49 high-risk and 18 low-risk infants
participated. Clinical assessment identified correctly almost all infants
with neurodevelopmental impairment including cerebral palsy (CP), but
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
did not predict if the infant would be affected by CP or not. The
kinematic analysis, in particular, the stereotypy score of arm movements, was an excellent predictor of CP, whereas stereotyped repetitive
movements of the legs predicted any neurodevelopmental impairment.
Conclusions: The automatic kinematic analysis of GMs is an excellent
predictor of CP; it outperforms clinical assessment of GMs. The automatic GM analysis identified movement parameters which are used
more or less intuitively by Gestalt perception during clinical GM
analysis.
FP011
New Neurodevelopmental Assessment for the
First Year of Life (SINA): The Neuromotor Scale
Pietz J.1, Philippi H.2, Tacke U.3, Rupp A.4, Hadders-Algra M.5
1
Zentrum für Kinder- und Jugendmedizin, Sektion
Neuropädiatrie, Heidelberg, Germany, 2SPZ FrankfurtMitte, Frankfurt, Germany, 3Universitäts-Kinderspital
Basel, Basel, Switzerland, 4Neurologische Klinik ‐ Sektion
Biomagnetismus, Heidelberg, Germany, 5Medizinisches
Zentrum UMCG ‐ Entwicklungsneurologie, Groningen,
Niederlande
Introduction: Neurodevelopmental assessments during the first year
are frequently performed with item sets which are composed by each
individual examiner guided by own experience. We report the construction and first evaluation of a standardized infant assessment (Standardized Infant NeuroDevelopmental Assessment; SINDA), which covers the
age range from 6 weeks to 12 months. It consists of the following three
parts: a neuromotor scale (30 items), a developmental scale (16 items
for each month), and a socioemotional scale. Method and Patients: In a
pilot study, we evaluated the results of 350 infants who had been
assessed with SINDA’s neuromotor scale in two outpatient clinics
(Heidelberg, Frankfurt). In a subgroup of 73 children who had reached
the age of at least 18 months, SINDA neuromotor results were correlated
with developmental outcome. Results: The total score and the subscale
scores of SINDA’s neuromotor scale did not correlate with age nor with
examination site. Factor analysis (VARIMAX) of all neuromotor items
resulted in eight independent factors which could be attributed to
comprehensible areas of function. The group of 73 children with
outcome data at the age of 18 months were classified on the basis of
the SINDA neuromotor score in the first year of life as normal (n ¼ 45),
mildly abnormal (n ¼ 10), and abnormal (n ¼ 18); on the basis of
outcome >18 months as normal (n ¼ 26), mildly abnormal (n ¼ 29), and
abnormal (n ¼ 18). The data indicated normal or mildly abnormal SINDA
scores did not predict normal or mildly abnormal outcome. In contrast,
abnormal SINDA scores (n ¼ 18) predicted abnormal outcome with high
accuracy (false negative 3/55 and false positive 3/18). Associated
sensitivity (0.83) and specificity (0.95) values were in the desired
high range. Conclusion: The first results on the validation of a newly
constructed infant neurodevelopmental assessment indicated that construct and predictive validity of the instrument are promising.
FP012
Dysarthria in Adults with Cerebral Palsy:
Clinical Presentation, Communication, and
Classification
Schölderle T.1, Staiger A.1, Lampe R.2, Strecker K.3,
Ziegler W.1
1
Klinikum Bogenhausen, Städtische Kliniken München,
Entwicklungsgruppe Klinische Neuropsychologie (EKN),
München, Germany, 2Klinikum Rechts der Isar, TU
München, Klinik und Poliklinik für Orthopädie und
Sportorthopädie, München, Germany,
3
Integrationszentrum für Cerebralparesen (ICP) München,
München, Germany
Background: Cerebral palsy (CP) is the most prevalent disorder in
neuropediatrics. About 80% of the patients show symptoms of dysarthria frequently resulting in major restrictions of everyday communication. However, to date, there is no comprehensive description of the
clinical features of dysarthria and their specific impact on communicative variables (e.g., intelligibility). Adult patients with CP have been
Abstracts
S5
Munich, 17th to 19th September 2014
FP013
Influence of Supply with Speech Generating
Devices on Health-Related Quality of Life in
Children with Cerebral Palsy: A Pilot Study
Schmidt N.1, Mall V.1, Berweck S.2,3, Nehring I.1,4, Jung N.1
1
Department of Pediatrics, Technische Universität
München, Kinderzentrum München gemeinnützige GmbH,
Munich, Germany, 2Schön Klinik Vogtareuth, Clinic for
Neuropediatrics and Neurorehabilitation, Vogtareuth,
Germany, 3Department of Pediatric Neurology and
Developmental Medicine, Hauner Children’s Hospital,
University of Munich, Munich, Germany, 4LudwigMaximilians-Universität München, Institute for
Socialpediatrics and Adolescent Medicine, Munich,
Germany
Question: Health-related quality of life (HRQL) in patients with cerebral
palsy (CP) is considered to be associated with the severity of the
communication impairment. The present controlled pilot study aims
to evaluate the influence of the supply with speech generating devices
(SGD) on HRQL in severely affected children and adolescents, according
to the Gross Motor Function Classification System Level IV-V (GMFCS)
with cerebral palsy (CP) and dysarthria. Method: We investigated n ¼ 14
patients with CP and GMFCS level IV-V, aged 7 to 19 years (12 $ 3.4
years). Seven patients were assigned to treatment group (group A) with
SGD and to the control group (B) without SGD, respectively. HRQL was
evaluated by the Caregiver Priorities and Child Health Index of Life with
Disabilities Questionnaire (CPCHILD). Results: Analysis of the “communication and social interaction” section revealed a higher HRQL in
patients with SGD (group A: mean item Score: 60.96 $ 13.84) as
compared to group B (mean item Score: 54.69 $ 9.25). Analysis of the
total score of the CPCHILD questionnaire displayed no change in HRQL
(group A: 51.07 $ 9.74; group B: 52.13 $ 8.12). Conclusions: Our results
point toward an influence of the supply with speech generating device
on HRQL in children with CP. This might correspond to better communication abilities, represented by the communication and social inter-
action section of the CPCHIL questionnaire. The preliminary data may
underline the importance of an adequate supply of these patients with
speech generating devices.
FP014
Comparison of Behavioral Problems in Children
and Adults with Cerebral Palsy
Weber P.1, Bolli P.1, Heimgartner N.1, Merlo P.1, Zehnder T.1,
Kätterer C.2
1
Universitäts-Kinderspital beider Basel, Neuro- und
Entwicklungspädiatrie, Basel, Switzerland, 2Rehab Basel,
Neurologie, Basel, Switzerland
Background: Cerebral palsy (CP) is the most common cause of motor
impairment in children frequently causing a lifelong disability. Behavioral problems are a common observed comorbidity, however, only few
data exist on this comorbidity in adults with CP. Aim This article aims to
compare the frequency of behavioral problems in patients with CP
between children and adults and to determine the relevance of the
developmental level. Methods: In a cross-sectional study, 40 children
(mean age, 9.6 years; range, 2.8-16.6 years) and 43 adults with CP (mean
age, 29.7 years; range, 18.1-58.0 years) were recruited. Both the groups
were assessed by the Strengths and Difficulties Questionnaire (SDQ), the
Parents/Caregiver Report Form of the Vineland Adaptive Behavior Scales
II (VABS), and the Child Behavior Checklist (CBCL). All questionnaires
were filled in by parents or caregivers. The type of CP was defined in
accordance with guidelines as spastic bilateral, spastic unilateral, atactic,
or dyskinetic. In the adults group, 58% fulfilled criteria for GMFCS level 4/
5, whereas in the children group only 16% shows this severe level of
impairment. Results: Children with CP have a significantly higher level
of behavioral problems in SDQ total compared with adults (mean, 19.4
vs. 13.9; p ¼ 0.003), although in the subgroups of SDQ no significant
difference exists. In contrast, adults show a lower level of prosocial
behavior in SDQ prosocial (mean, 5.5 vs. 6.9, p ¼ 0.029). In CBCL, the
most frequently reported pathological results (T value > 70) in the
children group are attention problems (29.7%), social interaction problems (29.7%), and thought problems (21.6%). In the adult group, the most
frequently reported problems are attention problems (28.0%), social
interaction problems (23.3%), and anxiety/depression (14.1%). In none of
the CBCL scales, a significant difference exists between the adults and
the children. In VABS in all groups, a significant difference with a
functional higher level in the group of children was reported: communication scale (mean, 64.6 vs. 37.4; p < 0.001); daily living skills (mean,
60.6 vs. 37.8, p < 0.001); socialization (mean, 65.0 vs. 43.2; p < 0.001).
Conclusion: In children as well as in adults, behavioral problem are
frequent. Children seem to show a higher functional behavioral level as
measured by VABS. However, as a limitation of our study in the group of
adults more patients show a higher level of impaired motor function,
which could influence this observation.
Genetics and Varia
FP015
Early Infantile Ataxia As Cardinal Symptom for
an X-Linked MECP2 Mutation
Zinck D.1, Biskup S.2, Vieker S.3
1
Marien Hospital Witten, Pädiatrie, Witten, Germany,
2
CeGaT GmbH, Tübingen, Germany, 3Marien Hospital
Witten, Witten, Germany
Case Report: This case study reports about two brothers who initially
showed a tremor as well as a slowly progressive ataxia since infancy.
Parents were healthy, not consanguineous. There are no neurological
diseases in the family history. Pregnancy was without complications and
normal early childhood development. They started walking at 12
months and developed speech like other children their age. The ability
to ride a bike was gained at the age of 3 years. In their second year, both
the children started to develop a fine intention tremor as well as
dysmetria with increasing limitation of fine motor skills plus a cerebellar
ataxia. Shortly after, nocturnal tonic-clonic seizures started to happen.
During infancy, one could notice mild developmental deficits combined
with autistic features. They initially started at a regular primary school
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
neglected particularly in the relevant literature, even though there are
several reports indicating that limitations of activity and participation
increase throughout adulthood due to functional deficits of speech.
Moreover, previous studies assume that the motor subtypes of CP
manifest in distinct symptom patterns of speech (dysarthria syndromes), which reflect the underlying pathomechanism (spasticity,
dyskinesia, and ataxia). This presumption is not confirmed by empirical
data. The aims of the study were (1) to systematically describe the
clinical presentation of dysarthria in adults with CP, (2) to identify
dysarthric symptoms that especially account for the communication
deficits, and (3) to compare patient groups with different CP types
regarding their dysarthria syndrome and the overall severity of the
speech and communication disorder. Methods: A total of 45 adults (age,
median ¼ 23 [18-56] years, 20 females) with different motor subtypes of
CP participated in the study. The Bogenhausen Dysarthria Scales provided a detailed neurophonetic profile for each patient. In several
listening experiments, we assessed two communication-relevant
parameters (intelligibility and naturalness). For dysarthria syndrome
classification, we applied a statistical approach. Results: A pronounced
severity of dysarthria became evident in the majority of patients. The
most prominent symptoms affected voice quality as well as articulatory
precision and rate. We documented substantial reductions of intelligibility and naturalness, which were predicted by articulatory and
prosodic features of dysarthria. Although the overall severity of the
speech and communication disorder differed between motor subgroups
(with patients of the dyskinetic variant of CP being more severely
affected), we found dissociations between CP type and dysarthria
syndrome in several cases. Conclusion: Adults with CP have to cope
with significant limitations of communication as a consequence of
dysarthric speech. Diagnostics and treatment should therefore target
communication-relevant aspects to orient toward the patients’ everyday social interactions. The motor subtype of CP provides only limited
information about the clinical presentation of dysarthria. For the
interpretation of this result, factors associated with the early brain
damage in CP might be considered.
S6
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Munich, 17th to 19th September 2014
Munich, 17th to 19th September 2014
but despite the support they were getting they had to change to a
special-needs school after 3 years. On top of the slowly progressive
ataxic disorder, the children are increasingly restricted by cognitive,
social, and emotional competence deficits as well as aggressive impulsive outbreaks in everyday life. Methods and Results: Electroencephalography (EEG): multiregional epilepsy-typical potentials (ETP),
activation during sleep, EEG seizure pattern bilateral frontal, frequent
nocturnal short clonic seizures, nerve conduction velocity (NCV), somatosensory evoked potentials (SEP), visual evoked potentials (VEP),
fundoscopy without pathological findings. Cerebral magnetic resonance
imaging (MRI) of the elder brother was done for four times and never
yielded pathological findings. Extensive metabolic diagnosis was unremarkable. Array comparative genomic hybridization without pathological findings was observed. Examination of the mother: no shift of Xinactivation in the range of androgen receptor was seen. Negative
mutation analysis for hereditary spinocerebellar ataxia and for ataxia
with oculomotor apraxia type 2 (AOA2) was also observed. At the
epilepsy-panel-diagnostics of both the children, we could detect a
mutation in the MECP2 gene variant c.419C>T;p.A140V (hemizygous).
Conclusion: Mutations in the MECP2 gene cause the X-linked dominant
Rett syndrome in female patients. MECP2 mutations can also cause
mental retardation of boys. The degree of severity depends on the
localization of the mutation in the gene. Some boys also show a typical
course of the disease (start of the regressive development between 6 and
18 months) and the characteristic stereotypy of the Rett syndrome (the
hand washing movement). In those cases, the mutations occur in form of
somatic mosaics. The cardinal symptoms of our case were the combination of cerebral ataxia and the early development of epilepsy during an
otherwise normal psychomotoric and mental development of the
infants. In this respect, MECP2 mutations should soon be considered
in differential diagnosis when ataxia occurs during infancy.
FP016
Sustained Unilateral Hand-Tapping in Girls with
Rett Syndrome: Interpretation of the
Electroencephalography
Herting A.1, Cloppenborg T.1, Bonse M.2, Kohl B.3, Polster T.1
1
Epilepsie-Zentrum Bethel/Krankenhaus Mara,
Kinderepileptologie Kidron, Bielefeld, Germany,
2
Evangelisches Krankenhaus Bielefeld, Klinik für Neurologie
Bethel, Bielefeld, Germany, 3Katholisches
Kinderkrankenhaus Wilhelmstift, Neuropädiatrie,
Hamburg, Germany
Rett syndrome in girls is characterized by mental regression with
autistic features and loss of purposeful hand use, which is replaced by
repetitive stereotypic hand movements, often described as hand washing. Epileptic seizures are common. Some girls with Rett syndrome show
a peculiar pattern of stereotyped tapping with one hand persisting over
months. The electroencephalography (EEG) shows correlated rhythmic
high-amplitude sharp waves. We describe a 6-year-old girl with classical
Rett syndrome. Her hand function during the first 15 months of life had
been relatively good and her global psychomotor development had been
less affected than in other girls. Myoclonic seizures started at the age of
17 months and were controlled by anticonvulsants. At the age of 4 years,
she started with sustained, rhythmic, and stereotyped tapping movements of her left hand that could transiently be stopped by holding her
hand. The EEG showed trains of rhythmic centrotemporal sharp waves,
creating a pattern that appeared like a “unilateral ESES in wakefulness.”
Video EEG and somatosensory evoked potentials could prove that the
EEG phenomenon is due to unilateral giant somatosensory evoked
potentials (SSEP), which could be evoked by tapping the fingers of
her left hand. The somatosensory evoked potentials showed giant
amplitudes on the same hemisphere. Giant SSEP and Sharp waves
elicited by somatosensory stimuli have been demonstrated in children
with idiopathic focal epilepsies. In our girl, one single situation with
these stimulus-induced rhythmic centrotemporal sharp waves showed
an evolution into a right-hemispheric seizure pattern with the clinical
correlate of a hypomotor seizure with tonic gaze deviation. We did not
see self-induced epileptic seizures—a well-known situation in patients
with reflex-epilepsies. A presumably small group of girls with Rett
syndrome shows a period of sustained, unilateral stereotypic tapping
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
movements in one hand accompanied by a pattern of centrotemporal
sharp waves in the EEG. Such a pattern is a marker of abnormal cortical
excitability in girls with Rett syndrome. It is not an ictal pattern and does
not require treatment.
FP017
Overlapping Phenotypes between Alternating
Hemiplegia of Childhood, Rapid-Onset
Dystonia-Parkinsonism, and CAPOS Syndrome
Rosewic H.1, Weise D.1, Ohlenbusch A.1, Gärtner J.1,
Brockmann K.2
1
Universitätsmedizin Göttingen, Klinik für Kinder- und
Jugendmedizin, Neuropädiatrie, Göttingen, Germany,
2
Klinik für Kinder- und Jugendmedizin,
Universitätsmedizin Göttingen, Sozialpädiatrisches
Zentrum, Göttingen, Germany
Background: Heterozygous mutations in the ATP1A3 gene are the
primary genetic cause of alternating hemiplegia of childhood (AHC)
and rapid-onset dystonia-parkinsonism (RDP and DYT12). Intermediate
AHC/RDP presentations and an expanding phenotypic variability become increasingly recognized. To delineate the phenotypic spectrum of
ATP1A3-related disorders, we performed mutation analysis also in
patients who do not express all classic AHC and/or RDP symptoms.
Patient: At the age of 20 months, an otherwise healthy boy with a
normal development suffered from an acute febrile episode with
impaired consciousness, anarthria, strabismus, generalized muscular
hypotonia and paresis of all limbs with accentuation of the right upper
arm. While consciousness and speech production recovered after a few
days, gait ataxia, as well as paresis and dystonia of the right arm
persisted over months with a gradual but complete recovery. At the
age of 6 years, another febrile episode of several days’ duration with
impaired consciousness, loss of speech and dysphagia, and generalized
muscular hypotonia occurred. Again, consciousness and speech production recovered within a week while a high-grade visual impairment,
ataxia, dysarthria, and dystonia persisted. Till today, at age 12 years, no
further episodes with paroxysmal neurologic deficits occurred. Optic
atrophy, sensorineural apical cochlear hearing loss, are flexia, ataxia,
and dystonia persisted over the years. Cranial magnetic resonance
imaging (MRI) and cerebrospinal fluid were normal. Biochemical and
genetic investigations provided no evidence for a mitochondrial disorder. Results: At the age of 11 years, the overlap of symptoms described
above with symptoms well known for AHC and RDP prompted to the
mutation analysis of the ATP1A3 gene. A novel de novo heterozygous
missense mutation (c.2452G>A [p.Glu818Lys]) was detected, which was
not found in 100 control alleles. The clinical picture of this patient first
appeared as an intermediate AHC/RDP phenotype. Very recently, this
particular ATP1A3 mutation c.2452G>A was identified as the primary
genetic cause of CAPOS syndrome (cerebellar ataxia, pes cavus, optic
atrophy, and sensorineural hearing loss) in 10 patients from three
families. Conclusion: This observation extends the phenotypic spectrum
of ATP1A3-related disorders and provides evidence for a phenotypic
overlap of AHC, RDP, and CAPOS syndrome.
FP018
Acute Onset of a Movement Disorder in Early
Childhood: A Family with Rapid Onset DystoniaParkinsonism Syndrome
Matzker E.1, Heinritz W.2, Traue C.3, Kurlemann G.4
1
CTK, Kinderklinik/ FB Neuropädiatrie, Cottbus, Germany,
2
Praxis für Humangenetik, Cottbus, Germany, 3Neuropäd,
Schwerpunktpraxis, Cottbus, Germany, 4UniversitätsKinderklinik Münster, Schwerpunkt Neuropädiatrie,
Münster, Germany
The Rapid Onset Dystonia Parkinsonism Syndrome is characterized by a
sudden onset of dystonia in combination with Parkinson like symptoms
as bradykinesia and postural instability. The typical affection pattern
shows a gradient from rostral to caudal with bulbar signs and an
insufficient response to l-Dopa. Frequently, triggers can be found (e.g.,
infections, fever, and emotional stress etc.). Dystonia-Parkinsonism
Syndrome (RPD) can be caused by several missense-mutations in
Abstracts
S7
Munich, 17th to 19th September 2014
FP019
Immunodeficiency, Centromeric Instability,
Facial Anomalies Syndrome Type 2 (ICF2):
Combined Immunodeficiency, Autoimmune
Phenomena, and Intellectual Disability
Ravindran E.1, Du H.2, Fröhler S.2, Strehl K.3, Kraemer N.1,
Issa-Jahns L.1, Fassbender J.1, Amulic B.4, Eirich K.5,
Schindler D.5, Chen W.2, von Bernuth H.3, Kaindl A.1
1
Department of Pediatric Neurology, Institut of Cell Biology
and Neurobiology, Charité, Berlin, Germany, 2MaxDelbrück-Centrum für Molekulare Medizin (MDC), Berlin,
Germany, 3Institute of Pediatric Immunology, Charité,
Berlin, Germany, 4MPI for Infection Biology, Berlin,
Germany, 5Institut für Humangenetik Biozentrum,
Würzburg, Germany
Introduction: The immunodeficiency, centromeric instability, facial
anomalies syndrome (ICF) is a rare autosomal recessive disease defined
by immunodeficiency, developmental delay, and facial abnormalities.
Centromeric instability results in chromosomal rearrangements and
genomic methylation is due to a defect. ICF1 and 2 are caused by biallelic
mutations in the DNA methyltransferase 3B gene DNMT3B and the zinc
finger and BTB domain-containing 24 gene ZBTB24, respectively. Patients without immunodeficiency but only with facial dysmorphism and
intellectual deficit exist. Objective and Methods: We describe the
detailed clinical, hematological, immunological, neurological, and cellbiological phenotype of a homozygous missense mutation with a
patient of the ZBTB24 gene (c.1222C > G, p.C408G) and thereby extend
the phenotype spectrum of ICF2. The cell viability, proliferation, and
apoptosis were assessed in nonimmune cells of the index patient.
Chromosome morphology by Giemsa staining was studied. Morphology
of cell cycle apparatus was analyzed by immunocytochemistry. The
effect of ZBTB24 gene mutation was further studied and confirmed
through siRNA. Results: In addition to previous reports, our patient
manifested with an isolated B-cell deficiency but later developed a
combined T-/B-cell immunodeficiency and features in line with autoimmune phenomena. We also demonstrate for the first time an impairment of the mitotic apparatus, proliferation, and survival of immune
and non-immune cells, which may contribute to the phenotype of ICF2.
Conclusion: These results suggest a generalized defect in cell proliferation and survival as underlying cause for the ICF2 phenotype. The
clinical course leading to liver cirrhosis and kidney failure calls for
consideration of early stem cell transplantation as an option in patients
with ICF2.
FP020
A Novel Mutation of the TRAPPC11 Gene Causes
a Disease with Cerebral Atrophy, Global
Retardation, Therapy Refractory Seizures,
Achalasia, and Alacrima: A Triple A-Like
Syndrome
Reschke F.1, Köhler K.1, Landgraf D.1, Susann K.1, Utine E.2,
Hazan F.3, Hübner A.1
1
Klinik und Poliklinik für Kinder- and Jugendheilkunde,
Pädiatrische Endokrinologie/Diabetologie, Dresden,
Germany, 2Pediatric Genetics Department, Ihsan
Dogramaci Children’s Hospital, Ankara, Germany,
3
Department of Medical Genetics, Dr. Behçet Uz Children’s
Hospital, Izmir, Turkey
Introduction: Triple A syndrome, also known as Achalasia-Addisonianism-Alacrima syndrome or Allgrove syndrome, is associated with mutations in the AAAS gene, which encodes for the protein ALADIN
(ALacrima Achalasia aDrenal Insuffiency Neurologic disorder). About
30% of the patients, suffering from the Triple-A syndrome offer no
mutation in the AAAS, confirming a genetic heterogeneity. We report
here about a novel mutation in the TRAPPC11 gene in four patients from
two unrelated families, suffering from a Triple-A-like syndrome.
TRAPPC11 is encoding for TRAPPC11 (Trafficking Protein Particle Complex subunit 11), a protein, which is a component of the TRAPP complex.
This multisubunit tethering complex is implicated in multiple intracellular vesicle trafficking steps. A downregulation of TRAPPC11 causes a
blocking of the intracellular secretory pathway, a partial disassembly of
the TRAPP complex and a fragmentation of the Golgi. Methods/Results:
Performing a genome wide linkage analysis of patients suffering from
Triple-A syndrome without a mutation in the AAAS gene, we detected a
linkage to a region of chromosome 4. A total of 26 genes, among them
TRAPPC11, are known to be located within this area. With whole exome
sequencing of the DNA of one of these patients, we identified a
homozygous splice mutation in TRAPPC11 (c.1893+3A>G). Using the
program MutationTaster, it could be proven that this mutation is
potential pathogenic and not a single nucleotide polymorphism
(SNP). This mutation could be identified in a second unrelated family
and segregates between these families. Characteristics of the patients
include a combination of cerebral atrophy, therapy-refractory epilepsy,
global retardation, scoliosis, achalasia, and alacrima. There was no
evidence for an underlying myopathy. Discussion/Conclusion: This
identified novel TRAPPC11 mutation (c.1893+3A>G) seems to cause a
new symptom complex, characterized particularly by neurologic disorders. If there is any linkage between this described phenotype and the
recently published TRAPPC11 mutations (c.2938G>A and c.1287
+5G>A), associated with the limb-girdle muscular dystrophy LGMD2S,1
will be analyzed in ongoing functional studies of TRAPPC11.
Reference
1 Bögershausen N, Shahrzad N, Chong JX, et al. Recessive TRAPPC11
Mutations Cause a Disease Spectrum of Limb Girdle Muscular
Dystrophy and Myopathy with movement Disorder and Intellectual
Disability. Am J Hum Genet 2013;93(1):181–190
FP021
Intrathecal Baclofen As an Effective
Antidystonic Treatment Option in Patients with
ARX-mutation: A Case Report
Selch C.1, Wimmer C.1, Jansen C.1, Betzler C.1, Berweck S.1,
Hackenberg A.2, Wohlrab G.3, Steinbeis von Stülpnagel C.1,
Staudt M.1, Kluger G.1
1
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Rehabilitation, Epilepsiezentrum für Kinder und
Jugendliche, Vogtareuth, Germany, 2Kinderspital Zürich,
Neuropädiatrie, Zürich, Switzerland, 3Univ. Kinderspital
Zürich, Neurologie/Elektrophysiologie und
Anfallssprechstunde, Zürich, Switzerland
Introduction: Mutations in the X-chromosomal ARX (Aristaless-related
homeobox)—gene cause epilepsy, genital malformations, mental
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Munich, 17th to 19th September 2014
ATP1A3 gene. Case Report: We present the case of a 15-month-old girl
with until this day normal development, admitted with a probable
febrile seizure after first MMRV vaccination. At time of admission, she
showed an impaired consciousness and a pathological movement
pattern. In the following hours, she developed signs of dystonia with
athetosis, bradykinesia with typical gradient, dysphagia as well as
intermittent but significant agitation. Blood and cerebrospinal fluid
samples as well as magnetic resonance imaging (MRI) and electroencephalography could not prove any sign of encephalitis. The mother of
the girl presented herself light signs of dysarthria and ataxia. According
to her, she had gone through encephalitis in early childhood as well as
her mother. Furthermore, her brother developed similar symptoms in
later childhood but not in that acute course. In the old documents of the
mother, there was described a similar acute disease at the age of 12
months. Therefore, we suspected an acute manifestation of an autosomal-dominant movement disorder. The genetic analysis confirmed the
mutation on the ATP3A1 gene for our girl and his mother. The grandmother was already deceased; the uncle refuses a genetic testing at that
time. Undergoing symptomatic therapy, we could state a spontaneously
stabilization of the symptoms, the further neurological development is
going to be observed. The typical age of onset of RPD ranges from 4 to 55
years. Early manifestations < 4 years of age have only been described in
combination with a variant of RPD beginning initially with motor delay,
ataxia, and muscular hypotonia. Our family presents an unusual early
manifestation of the acute onset type of RPD. The clinical features are
demonstrated by video.
S8
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Munich, 17th to 19th September 2014
retardation, structural brain malformations, and also dystonia. Dystonia
in patients with ARX mutations is often severe, may be difficult to
distinguish from epileptic seizures and significantly impairs the patients’ daily activities and quality of life. We report our experience with
intrathecal Baclofen as an antidystonic therapeutic approach in a patient
with ARX mutation. Patient: Dystonia in the 6-year-old patient with a
de novo mutation in the ARX gene (c.315_335dup;p.Ala109_Ala115dup)
developed at the age of 3 months and severely affected the patient’s
daily activities. Furthermore, one episode of dystonic storm with
rhabdomyolysis was reported. Oral antidystonic drugs showed no
satisfactory effects (baclofen orally, l-Dopa) or even caused deterioration
(tetrabenazine). Because of the severity of the symptoms, the patient
was chosen as a candidate for intrathecal baclofen therapy (ITB), as ITB
had previously been proven effective in another patient with ARXassociated dystonia (Dr. G. Wohlrab, MD, personal oral communication).
Methods: Individual goals of everyday life were defined via Goal
Attainment Scale (GAS). An extensive analysis of the dystonic movement disorder before and after surgery was performed via Barry Albright Dystonia Score (BAS) and video documentation. To evaluate the
health-related quality of life, the CPCHILD questionnaire (Available at:
http://www.sickkids.ca/Research/CPCHILD-Questionaire/CPCHILDProject/index.html) was used before and after the start of ITB. Results:
The patient responded very well even to a relatively low dose of 150 µg
baclofen i.t./d (Medtronic Synchromed II, 20 mL, Simple Continuous
Mode); the dystonic movement disorder improved considerably. While
the BAS was still unchanged 3 weeks after surgery (28/28 points),
CPCHILD showed significant improvement of the health-related quality
of life (total score preoperative 18/100, postoperative 49/100). In the
GAS, expectations were met (1/4), respectively exceeded (3/4) in all four
items. Discussion: Intrathecal Baclofen was an effective antidystonic
treatment option in our patient with ARX-mutation which led to
significant—and objectively measurable—improvement of the patient’s
quality of life. In summary, ITB has now been successfully applied in two
patients with ARX-associated dystonia.
FP022
A Good View at Proper Diagnosis: Onodi Cell As
Rare Cause of Optic Neuritis
Elpers C.1, Niederstadt T.2, Schwartz O.1, Fiedler B.1,
Kurlemann G.1
1
Klinik für Kinder- und Jugendmedizin,
Universitätsklinikum Münster, Allgemeine Pädiatrie,
Bereich Neuropädiatrie, Münster, Germany, 2Institut für
Klinische Radiologie, Universitätsklinikum Münster,
Münster, Germany
The sphenoethmoidal cell (Onodi cell) is a quite posterior ethmoid cell
with more cranial and dorsal extension which leads to dorsal displacement of sphenoidal sinus. Onodi cell shows very close proximity
(medial, cranial, and caudal) to the optic canal respectively to the optic
nerve. We present the case of a 5-year-old boy with right rhinogenic
optic neuritis (RON) secondary to sinusitis of the Onodi cell. Three
months before initial presentation at our department, intermitted pupil
dilation of his right eye is recognized by parents. Ophthalmologist
diagnoses optic atrophy of the right eye and further diagnostic is
initiated. Cerebrospinal fluid (CSF) shows positive oligoclonal bands
(type 3—identical oligoclonal bands in CSF and serum). Magnetic resonance imaging (MRI) confirms right optic neuritis and shows single
periventricular white matter lesions without gadolinium enhancement.
Further diagnostic reveals no pathological findings (pathogen diagnostics, spinal MRI, aquaporin-4-AK, and genetic testing of Leber hereditary
optic atrophy). Treatment with intravenous cortisone pulse therapy
with oral tapering over 2 weeks shows no significant improvement of
visual acuity. MRI after 6 months shows no atrophy of the right optic
nerve and no white matter lesions. At that time, the patient is referred to
our neuropediatric department with persistent-reduced visual acuity
and optic atrophy on the right eye. He presents with clear relative
afferent pupillary defect, visual acuity of 0.1 and optic atrophy on the
right eye. No fixation is possible after covering the nonaffected eye.
Visual-evoked potentials are absent on the right eye. There is no history
of visual loss, retrobulbar pain, or neurological impairment. Retrospective analysis of cerebral MRI reveals a sphenoethmoidal cell (Onodi cell)
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
intimately related to the right optic nerve, with acute sinusitis. Surgical
resection of Onodi cell is discussed but evaluated as nonappropriate
approach because of already existing optic atrophy. To our knowledge,
this is the first published case report of isolated RON in childhood caused
by sinusitis of Onodi cell. Inflammation of Onodi cell (sinusitis and
mucocele) should be included in the differential diagnosis of optic
neuritis in children. Additional thin-layer MRI sequences in the region
of the optic nerves should be considered to confirm the diagnosis.
Surgical decompression has to be discussed individually.
FP023
Using Advanced MR Methods for the
Assessment of Children Before Undergoing
Brain Surgery
Wilke M.1, Groeschel S.1, Rona S.2, Schuhmann M.2,
Ernemann U.3, Krägeloh-Mann I.1
1
Universitätsklinikum Tübingen, Neuropädiatrie,
Entwicklungsneurologie, Sozialpädiatrie, Tübingen,
Germany, 2Universitätsklinikum Tübingen, Klinik für
Neurochirurgie, Tübingen, Germany, 3Universitätsklinikum
Tübingen, Klinik für diagnostische und Interventionelle
Neuroradiologie, Tübingen, Germany
Introduction: Advanced magnetic resonance (MR) methods such as
functional and diffusion MRI allow for the delineation of eloquent
cortex and white matter fiber tracts, respectively. As such, they have
become important tools in the assessment of patients before undergoing
neurosurgical interventions. However, these approaches are both challenging to implement and difficult to administer in children. We here
report on our efforts to implement a structured advanced MR program
for the presurgical assessment of children. Methods: Over the course of
10 years, a total of 79 children were imaged on a 1.5 T Siemens MR
scanner (either Sonata or Avanto; Siemens, Erlangen, Germany). Investigations were performed as part of a scientific study; functional series
were acquired in 76 children, using the locally established, childfriendly fMRI paradigms, and data was processed using statistical
parametric mapping (SPM). In addition or alternatively, diffusion MRI
data were acquired in 28 children, using a high angular resolution
sequence (60 directions) for advanced probabilistic fiber tracking, and
data was processed using MRtrix. There were 41 girls and 38 boys, and
mean age was 11.6 $ 4.0 years. Results: In our cohort, the most common
presentation was with tumorous brain lesions (n ¼ 27), malformations
of cortical development (n ¼ 17), or cavernomas (n ¼ 4). Most children (n
¼ 62) suffered from epilepsy. Primary indications for imaging were the
assessment of the language domain (n ¼ 57) followed by hand motor
function (n ¼ 14) and the visualization of the corticospinal (n ¼ 3) and
optic radiation white matter tracts (n ¼ 5). Overall, data could successfully be interpreted in 72 children, with lack of cooperation, subject
motion, and technical problems representing the reasons for failure (n ¼
7). Conclusions: Although increasingly recognized to be an integral part
of a comprehensive, state-of-the-art presurgical assessment, the technical and practical challenges of performing clinically indicated functional and diffusion MRI scans have yet precluded a wider use of these
methods in children. We here demonstrate that, in close cooperation
between pediatricians, neuroradiologists, and neurosurgeons in a tertiary referral center, a clinical program to this effect can successfully be
implemented. In the large majority of subjects (91%), at least one of the
questions posed to the exam could be answered. The necessary prerequisites as well as some of the obstacles and our approaches to dealing
with them will be presented.
Abstracts
S9
Munich, 17th to 19th September 2014
GNP Opening
FP024
Modulation of Vasculogenesis under rhEPO
Therapy Following Acute Cerebral Hypoxia in
the Mouse
Richter-Kraus M.1, Jung S.1, Brackmann F.1, Trollmann R.1
1
Kinder- und Jugendklinik des Universitätsklinikums,
Neuropädiatrie, Erlangen, Germany
FP025
The Impact of Timing of Microglial Activation by
Inflammation and Hypoxia Regarding Additive
Neurotoxic Effects
Jung S.1, Frey D.1, Brackmann F.1, Richter-Kraus M.1,
Trollmann R.1
1
Division of Neuropediatrics, Department of Paediatrics
and Adolescent Medicine, University Hospital of the
Friedrich-Alexander University, Erlangen, Germany
Introduction: Perinatal cerebral hypoxia and endotoxins are main risk
factors for acquired brain injury and neurological disabilities. Here, we
investigated the impact of lipopolysaccharide stimulated microglia on
inflammation and cytotoxicity in vitro in the context of hypoxia.
Methods: BV2 cells were exposed to LPS and hypoxia (1% O2). Expression of the transcription factor hypoxia-inducible factor (HIF)-1α as well
as of iNOS, IL-1b, IL-6, and tumor necrosis factor (TNF)-α were analyzed
by real-time polymerase chain reaction, western blot, and enzymelinked immunosorbent assay. NO production was quantified by the
Griess assay. Results: LPS exposition prior hypoxia increased mRNA and
protein expression of HIF-1α, iNOS, and inflammatory cytokines suggesting synergistic regulation of hypoxia and inflammatory signaling
pathways in microglial cells. Whereas HIF-1α accumulation was transient depending on the presence of LPS, ongoing cytokine and NO
secretion was observed for at least 3 days after LPS removal. Notably,
hypoxia potentiated the LPS-induced secretion of IL-1b (22-fold), IL-6
(threefold), TNF-α (threefold), and increased NO production by approximately 60%. Cell-free supernatants derived from LPS exposed BV2 cells
Neuromuscular and Metabolic Diseases and Varia
FP026
Results of a Phase II Study to Assess Safety and
Efficacy of Olesoxime (TRO19622) in 3- to 25Year-Old Spinal Muscular Atrophy Patients
Kirschner J.1, Dessaud E.2, André C.3, Scherrer B.4, Pruss R.2,
Cuvier V.2, Hauke W.2, Müller-Felber W.5, Schara U.6, Walter
M.7, Bertini E.8
1
Universitätsklinikum Freiburg, Neuropädiatrie und
Muskelerkrankungen, Freiburg, Germany, 2Trophos SA,
Marseille, Frankreich, 3Association Française contre les
Myopathies (AFM), Evry, Frankreich, 4Bruno Scherrer
Conseil, Saint-Arnoult-en-Yvelines, Frankreich, 5LMU Dr.
von Haunersches Kinderspital, Neuropädiatrie, München,
Germany, 6Universitätsklinikum Essen, Kinderklinik1,
Bereich Neuropädiatrie, Entwicklungsneurologie und
Sozialpädiatrie, Essen, Germany, 7Friedrich-Baur-Institut,
Neurologische Klinik und Poliklinik, LMU München,
München, Germany, 8IRCCS Ospedale Pediatrico Bambino
Gesù, Dipartimento di Neuroscienze, Rom, Italien
Background and Objectives: Olesoxime (TRO19622) was identified as a
potential treatment of spinal muscular atrophy (SMA) based on its
beneficial effects in multiple preclinical neurodegeneration models.
Olesoxime promotes neuron survival, neurite outgrowth, recovery
from nerve injury and accelerates myelination or remyelination in models
of demyelinating diseases. Maintaining motor neuron architecture and
survival is highly relevant to SMA, a disease associated with progressive
motor neuron compromise mainly affecting neuromuscular function. A
clinical study has been performed to evaluate the effects of olesoxime
treatment in patients with SMA. Results: A total of 165 type 2 or
nonambulant type 3 SMA patients, aged 3 to 25 years were enrolled
from 22 sites in seven European countries starting in November 2010.
Patients were randomized to olesoxime, 10 mg/kg, administered as a
liquid oral formulation or matching placebo in a 2:1 ratio and treatment
duration was for 104 weeks. The last patient completed the study in
October 2013. The primary outcome measure was the change in motor
function using the motor function measure scale. The secondary outcome measures included the Hammersmith Functional Motor Scale for
SMA, electromyography, pulmonary function, and patient-reported
outcomes as well as safety. Patients in the placebo arm of the study
experienced a loss of motor function at a similar rate to that previously
reported.1 Conclusions: Results from this pivotal double blind placebocontrolled clinical trial provide clinical proof of concept of olesoxime’s
neuroprotective effect that is sustained over 2 years. This combined with
good tolerability of the treatment will be submitted for the registration
of olesoxime as the first neuroprotection treatment for SMA. In addition,
the collected data will provide a valuable source of longitudinal data for
motor function and potential prognostic biomarkers in a broad range of
SMA patients. Acknowledgments: AFM-Téléthon, SMA Foundation,
families of SMA, and special thanks to all the investigators, patients,
and their families who participated in the clinical trial.
Reference
1 Vuillerot C, Rippert P, Roch S, et al. Development and validation of a
motor function classification in patients with with neuromuscular
disease: The NM-Score. Ann Phys Rehabil Med 2013;56(9-10):673–686
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Background: Hypoxic-ischemic insults are a major cause of perinatal
acquired central nervous system lesions and modulate vasculogenesis and
angiogenesis of the immature brain. To assess the efficacy of neuroprotective
therapies, proapoptotic effects as well as a comprehensive analysis of vessel
formation and vessel development are essential. Against this background,
we investigated the effect of a pharmacological stabilization of the system of
hypoxia inducible factors (HIFs) by recombinant human erythropoietin
(rhEPO) in a mouse model of neonatal acute systemic hypoxia. Methods:
Neonatal C57BL/6NCrl mice (7 days) were exposed for 6 hours to acute
systemic hypoxia (8% O2) or normoxia (21% O2) (InVivo2 400; Ruskin,
Leeds, United Kingdom). At 0, 24, and 48 hours, the intraperitoneal
injection of rhEPO (NeoRecormon, Roche 2500/5000 IU/kg) was performed. The expression of vasogenic factors was analyzed after a
reoxygenation-periode of 72 hours by real-time polymerase chain
reaction (VEGF-A, VEGFR-1, VEGFR-2, Nrp-1, Nrp-2, ANG-1, ANG-2,
and TIE-2) as well as regions specific in the parietal cortex and the
hippocampus by RNA in situ hybridization (VEGF-A). The analysis of
vascular development (PECAM-1 IHC; vessel length, branching, and
area) was performed using AxioVision/reconstruction-software Imaris.
Results: Under normoxia, there were no significant changes of cerebral
mRNA expression of VEGFR-1, VEGFR-2, Nrp-1, Nrp-2, ANG-1, and TIE-2
in due to rhEPO comparison to controls, however, rhEPO led to a
significant reduction of ANG-2 mRNA levels, and consequently to an
increase of ANG-1/ANG-2 mRNA ratio in favor of ANG-1 stabilizing vessel
structure. In addition, rhEPO induced a significant increase of cortical
vessel length, branching and area associated with a marked increase of
VEGF-A mRNA concentrations (up to 300%). Hypoxia resulted in a
significant suppression of hypoxia-inducible VEGF-A mRNA expression
(p < 0.001). Compared with controls, rhEPO induced under hypoxia a
significant increase in ANG-1/ANG-2 mRNA ratio up to 3.5-fold (p <
0.001). Summary: Our data imply a protective effect of rhEPO on cerebral
vascular development after acute hypoxia in the immature mouse brain.
rhEPO seems to regulate the VEGF-A, ANG-1, and ANG-2 expression
hypoxia-inducible factor independently via an alternative pathway.
were highly cytotoxic. Again, hypoxia enhanced the cytotoxic effect
significantly. In contrast, stimulation of BV2 cells by hypoxia prior LPS
abolished additive inflammatory neurotoxic effects compared with
controls (p < 0.01). Conclusion: Present in vitro data indicate that LPS
induces a dose-dependent and long-lasting sensitization of BV2 cells to
hypoxia. Enhanced cytokine and NO secretion may contribute to delayed
glial damage following cerebral hypoxic insults during the perinatal period.
As hypoxia induced accumulation of the neurotrophic transcription factor
HIF-1α abolishes cytotoxic inflammatory effects, present observations may
have implications for neuroprotective pharmacological strategies.
S10
Abstracts
Munich, 17th to 19th September 2014
FP027
Juvenile Dermatomyositis: Analysis of a Single
Muscular Center Cohort
Della Marina A.1, Lutz S.1, Trippe H.1, Schweiger B.2,
Neudorf U.3, Schara U.1
1
Neuropädiatrie, Entwicklungsneurologie und
Sozialpädiatrie, Universitätsklinikum Essen, Essen,
Germany, 22Institut für Diagnostische und Interventionelle
Radiologie und Neuroradiologie Universitätsklinikum
Essen, Essen, Germany, 3Pädiatrische Kardiologie,
Universitätsklinikum Essen, Essen, Germany
Munich, 17th to 19th September 2014
Background: Juvenile dermatomyositis (JDM) is a systemic, inflammatory disease of unknown etiology. The combination of muscular weakness and typical skin rash are characteristic features of the disease. The
skin lesions can often be very mild pronounced or even absent and
therefore the patients may be presented with the diagnosis of indistinct
muscle weakness. Methods: Retrospective review of patients diagnosed
with JDM between 2007 and 2014. Results: A total of 13 patients (six
women and seven men) were identified, and the median age at
diagnosis was 7.9 years. In all the patients, the diagnosis was confirmed
by magnetic resonance imaging (MRI) and muscle biopsy (MB), which
showed in all disease-specific inflammatory changes. At diagnosis, 8 of
13 patients had abnormal creatine kinase (CK) level, the skin lesions
were variable pronounced in 11 of 12 patients. All patients reported
muscle weakness, easy fatigue, and muscle pain as the main symptoms,
two patients had recurrent fever at the beginning. One patient had,
during this period, her second relapse of the disease; and two patients
developed the chronic form of the disease. All patients received intravenous steroid pulses and methotrexate therapy, in addition 7 of 13 oral
steroids, 2of 13 cyclosporin A, one patient azathioprine, intravenous
immunoglobulin, mycophenolate mofetil, and rituximab. Of the 13
patients, 5 showed normalization in the course of the MRI findings,
however, significantly delayed compared with clinical improvement.
The time between the onset of symptoms and diagnosis ranged from 4
weeks to 5 years, an average of 9 months. In one boy, the diagnosis was
established 5 years after symptom onset. He developed massive subcutaneous calcinosis with abscess formation, which showed regression
tendency under therapy with methylprednisolone and bisphosphonates. Conclusion: Although all patients had clinical symptoms suggestive of JDM, the diagnosis was established in only 2 of 12 patients within
the first month after the onset of the first symptoms. In case of sudden or
slowly progressive muscle weakness in combination with muscle pain,
with or without skin lesions in previously healthy children JDM must be
suspected, even at normal CK levels. After affirmation of the diagnosis by
MRI and MB, an early, in our muscular center standardized therapy,
shows a positive effect on the course of the disease.
FP028
Broad Phenotypic Spectrum of ADystroglycanopathies due to POMT1 Mutations
in 16 Families
Geis T.1, Müller-Felber W.2, Schirmer S.3, Topaloglu H.4,
Hehr U.5
1
Klinik und Poliklinik für Kinder- und Jugendmedizin der
Universität Regensburg (KUNO), Neuropädiatrie,
Regensburg, Germany, 2Dr. von Haunersches Kinderspital,
Ludwig-Maximilians-Universität, München, Germany,
3
Zentrum für Humangenetik Regensburg, Regensburg,
Germany, 4Department of Pediatric Neurology, Hacettepe
University, Ankara, Turkey, 5Institut für Humangenetik,
Universität Regensburg, Regensburg, Germany
Introduction: Congenital muscular dystrophies with defective O-glycosylation of α-dystroglycan (α-dystroglycanopathies) are a heterogeneous group of autosomal recessive inherited disorders explained by
mutations in an increasing number of related genes. Among those,
POMT1 was initially associated with Walker-Warburg syndrome (WWS)
at the most severe end of the disease spectrum. Subsequently, milder
POMT1-associated phenotypes such as congenital muscular dystrophy
(CMD) or limb girdle muscular dystrophy (LGMD) have been described.
In an ongoing study, we aim to further characterize the genotypephenotype correlation and genotype-dependent long-term course of
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
patients with genetically confirmed forms of those dystroglycanopathies and here present the wide clinical spectrum of POMT1-associated
phenotypes. Methods: Evaluation of the patients’ medical reports and
MRI as available were done. Linkage analysis for suitable families, Sanger
sequencing, and more recently targeted or exome next generation
sequencing were evaluated. Results: POMT1 mutations were identified
in 22 patients from 16 families including 12 patients or fetal samples
from 7 families with suspected WWS, 9 patients from 8 families with
suspected LGMD2K, and 1 patient clinically classified as CMD. Interestingly, among WWS patients exclusively homozygous or compound
heterozygous truncating mutations were observed. Three WWS families
had two or more affected offspring showing a uniformly fatal prenatal
presentation with severe hydrocephalus. In three WWS families, prenatal diagnosis was requested in subsequent pregnancies. Two patients
with LGMD2K and the CMD patient were compound heterozygous for
one missense mutation and one truncating POMT1 mutation. A rather
uniform LGMD2K phenotype with proximal muscle weakness and
cognitive impairment was observed in patients from six families
homozygous for the POMT1 mutation p.Ala200Pro. The CMD patient
had a neonatal disease onset with muscular hypotonia and subsequently
delayed motor development and substantial cognitive impairment
without brain MRI abnormalities. During the first decade of life, his
phenotype was suggestive of Duchenne muscular dystrophy with creatine kinase values above 5,000 U/L. However, he had an unusually slow
progression of his proximally pronounced CMD and a preserved ability
to walk into his early thirties. His genetic diagnosis was finally confirmed at the age of 32 years. Conclusion: Our data suggest a genotypephenotype correlation for POMT1 with homozygous or compound
heterozygous truncating mutations resulting in WWS while the presence of at least one missense mutation is associated with a milder
phenotype. Mutations in POMT1 and other related genes should also be
considered in adult LGMD and CMD patients, in particular, in those with
associated cognitive and psychomotor delay with or without structural
brain abnormalities.
FP029
Severe Case of Congenital Myasthenic
Syndrome with Novel Mutations in MUSK
Giarrana M.1, Joset P.2, Robb S.3, Steindl K.2, Rauch A.2,
Klein A.1
1
Department of Paediatric Neurology, University Children's
Hospital, Zürich, Switzerland, 2Institute of Medical
Genetics, University of Zurich, Schlieren, Switzerland,
3
Department of Neurosciences, Dubowitz Neuromuscular
Centre, London, United Kingdom
Question: Congenital myasthenic syndromes are rare conditions. So far,
18 causative genes are known. Mutations in MUSK are very rare, since
the first description in 2004 only 13 patients have been reported, mostly
with a relatively mild course. The molecular diagnosis has implications
for the choice of treatment, and genetic counselling. Methods: Case
report Results: We describe a now 4-year-old boy with a severe and
early manifestation of the disease with two novel mutations in MUSK
detected by exome sequencing. He presented with prenatal onset and
severe respiratory symptoms leading to tracheostomy and the need for
ventilation until now. In addition, he shows marked axial weakness with
a dropped head syndrome, some facial and proximal weakness and
severe bulbar symptoms requiring complete tube feeding. Ophthalmoparesis developed at age 9 months. As described before, treatment with
salbutamol and later added 3.4-diaminopyridine lead to improvement.
A short trial of pyridostigmine in infancy led to bradycardias necessitating resuscitation. Conclusions: We expand the described phenotype
of patients with congenital myasthenic syndrome with MUSK mutations. A more severe phenotype with prenatal onset is possible. Predominant bulbar and respiratory weakness with later development of
facial, axial weakness, and ophthalmoparesis point to the diagnosis.
Abstracts
S11
Munich, 17th to 19th September 2014
FP030
Sensory Autonomic Neuropathy with Analgesia
and Gastroenterological Symptoms due to a
Mutation in the SCN11A Gene
Korenke G.1, Marquardt I.1, Leiphold E.2, Bergmann M.3,
Kurth I.4
1
Zentrum für Kinder- und Jugendmedizin/Klinikum
Oldenburg, Klinik für Neuropädiatrie, Oldenburg, Germany,
2
Institut für Molekulare Biomedizin, Jena, Germany,
3
Insititut für Neuropathologie, Bremen, Germany, 4Institut
für Humangenetik, Jena, Germany
References
1 Leipold E, Liebmann L, Korenke GC, et al. A de novo gain-of-function
mutation in SCN11A causes loss of pain perception. Nat Genet
2013;45(11):1399-8211
2 Zhang XY, Wen J, Yang W, et al. Gain-of-function mutations in
SCN11A cause familial episodic pain. Am J Hum Genet 2013;93
(5):957-966
FP031
iNTD: Deep Phenotyping of Inborn Errors of BH4
and Neurotransmitter Metabolism and
Evidence-Based International Treatment
Guidelines
Opladen T.1
1
Zentrum für Kinder- und Jugendmedizin, Sektion für
angeborene Stoffwechselerkrankungen, Heidelberg,
Germany
FP032
Development of Neuropsychological Functions
in Patients with Glutaric Aciduria Type I
Boy N.1, Heringer J.1, Haege G.1, Glahn E.1, Hoffmann G.1,
Burgard P.1, Kölker S.1
1
Zentrum f. Kinder-/Jugendmedizin Heidelberg, Allgemeine
Pädiatrie, Sektion f. angeborene Stoffwechselstörungen,
Heidelberg, Germany
Background: Glutaric aciduria type I (GA-I) is an autosomal recessive
inherited metabolic disease due to a deficiency of glutaryl-CoA dehydrogenase, which if untreated results in severe neurological impairment. Combined metabolic treatment (low-lysine diet, carnitine
supplementation, and emergency treatment) according to evidencebased guideline recommendations (Kölker et al 2011) has significantly
reduced the manifestation of striatal injury and secondary dystonia in
glutaric acidemia type I (GA-I) patients. However, development of
cognitive functions in these patients has not yet been studied in detail.
Methods: In a cross-sectional design, 31 patients detected by newborn
screening (n ¼ 13), high-risk family screening (n ¼ 3), or selective
screening (n ¼ 14) were tested for the following: (1) Simple reaction
time (SRT), (2) continuous performance (CP), (3) visual working memory (VWM), (4) tracking (T), and (5) visual search (three loads: VS1, VS2,
and VS3). Dystonia, observed in 13 patients (42%), was categorized for
severity using the Barry-Albright Dystonia Scale (BADS). Patients’ data
were compared with a cross-sectional control group of 196 healthy
subjects covering the same age range. Developmental functions of
cognitive performance were analyzed using a negative exponential
function model. Results: Compared with asymptomatic patients dystonic patients showed poorer performances in speed motor tests (SRT
and tracking). Tests with higher cognitive load (CP, VWM, and VS) were
not associated with BADS score. Development of cognitive performance
in GA-I patients did not differ from healthy control for mean CP, tracking,
and VWM but in contrast was different for SRT and VS3; data fitted
equally well to a negative exponential function. However, patients in
younger age groups performed consistently poorer but consistently
caught up with age. Conclusion: In summary, our results show that
dystonia in GA-I patients results predominantly in motor speed impairment, but not in information processing like memory. Furthermore,
stability of speed is comparable to healthy subjects, in particular
showing no decline over time. Results indicate normal developmental
functions in GA-I patients, however, with increased reaction times.
Background: Neurotransmitters are chemical messengers, which mediate, amplify, or modulate synaptic transmission. BH4 is the essential
cofactor for the biosynthesis of the neurotransmitters dopamine and
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
We report on a girl at the age of 12 years, which was admitted for first
time to our hospital at the age of 8 months. At her first presentation, she
showed gastrointestinal problems with failure to thrive, enhanced
sweating, hyperkinetic movement disorder, and muscle hypotonia.
The gastroenterological examinations were unremarkable—even
electroencephalography, cranial magnetic resonance imaging, neurometabolic diagnostics, and muscle biopsy showed no pathological
changes. In a follow-up examination at the age of 21 months, the mother
reported that the patient had bitten off the tip of her tongue during a
candida mycosis. Only at this time, it turned out that the patient has no
pain perception. The sensory nerve conduction velocity was decreased.
The histamine test was pathological. In the nerve biopsy, a slight
decrease of myelinated fibers was observed. In the further clinical
course, bone fractures occurred and chronic skin lesions have developed, which are associated with necrosis from recurrent tissue damage
and severe mutilations. The motor development was clearly delayed,
while the cognitive development was only slightly retarded. The
gastroenterological symptoms disappeared, while the analgesia persisted. All previously known genetic causes of hereditary sensory
autonomic neuropathies were excluded. Using exome sequencing, a
heterozygous de novo missense mutation in the SCN11A gene was
detected (c.2432T> C; p.Leu811Pro). SCN11A encoded a sodium 1.9voltage-controlled channel, which is predominantly expressed in nociceptors. In animal models, it has been shown that mice with the same
mutation show a reduced sensitivity to pain. The detected gain-offunction mutation leads to persistent depolarization of the nociceptors
and therefore to reduced formation of action potentials and an impaired
synaptic transmission. In a worldwide search for patients with congenital analgesia of unknown origin, the identical mutation in SCN11A gene
could be detected in a Swedish boy with autonomic neuropathy,
analgesia, and gastroenterological symptoms.1 Mutations in sodium
channels cause a variety of neurological and cardiac disorders. The
examinations of the presented patient have shown for the first time that
a gain-of function mutation in the SCN11A gene leads to a sensory
autonomic neuropathy with analgesia and gastroenterological symptoms (Leipold et al 2013). Meanwhile, SCN11A loss of function mutations
has also been described in familial episodic pain syndromes.2
serotonin. Inborn errors of BH4 and neurotransmitter metabolism are
treatable disorders. Without therapy, they lead to movement disorders,
muscular hypotonia, and retardation in early infancy. Immediate diagnosis and treatment initiation result in an improved outcome. Until
today, there is no standardized long-term follow-up of the patients nor
exist international guidelines for the standardized diagnosis and treatment of inborn errors of BH4 and neurotransmitter metabolism. Project
Outline: For this project, a new cooperation between European reference centers from Heidelberg, London, Barcelona, Paris, Innsbruck, und
Rome (International Working Group on Neurotransmitter related Disorders (iNTD); www.iNTD-online.org) was established. The consortium
will collect data on the actual diagnostic and therapeutic approaches as
well as on the long-term prognosis and quality of life of patients with
inborn errors of BH4 and neurotransmitter metabolism. The aim is to
characterize deeply the phenotypic spectrum of these diseases. In
addition, the group will establish within 3 years international S2
guidelines for the treatment of inborn errors of BH4 and neurotransmitter metabolism. Conclusion: To optimize patients care and disease
outcome, the iNTD group will perform deep phenotyping of inborn
errors of BH4 and neurotransmitter metabolism and establish international evidence-based guidelines for these diseases.
S12
Abstracts
Munich, 17th to 19th September 2014
Ataxia in Creatine Deficiency Syndrome
FP033
Waldmeier S.1, Slotbloom J.2, El-Koussy M.2, Springer E.2,
Weisstanner C.2, Steinlin M.1
1
Universitäre Kinderklinik Bern, Neuropädiatrie, Bern,
Switzerland, 2Universitätsinstitut für Diagnostische und
Interventionelle Neuroradiologie, Bern, Switzerland
Munich, 17th to 19th September 2014
Creatine deficiency syndrome represents a rare, probably underdiagnosed but treatable metabolic problem with increasing awareness of
different clinical manifestations. There are three syndromes. The most
typical manifestation consists of mental retardation, seizures, and
extrapyramidal symptoms or hypotonia. Ataxia as exclusive motor
impairment is rarely reported. Case Report: We present the case of a
10-year-old girl of consanguineous parents in which developmental
delay became evident around the age of 15 months. Initial motor delay
was followed by mild ataxia at the age of 3.5 years. Marked cognitive
problems with absence of speech acquisition and autistic features
became evident during the course. There was no clear episode of
regression. No epileptic seizures were reported until today. Magnetic
resonance imaging was normal, but spectroscopy of the brain was
diagnostic by revealing a completely missing creatine and phosphocreatine peak. Laboratory work-up by measurement of guanidinoacetate in
serum and creatine/creatinine ratio as well as genetic analyses for
classifying the subtype and confirmation of the diagnosis is in process.
Creatine substitution was started. Conclusion: Typical symptomatology
for cerebral creatine deficiency syndrome is initial hypotonia followed
by an extrapyramidal movement disorder, accompanied by seizures,
developmental problems, and frequently autistic features. Our child
represents one of the rare cases, where isolated ataxia was the only
movement disorder. Interestingly, there is one report on patients with
episodic ataxia type 2 and reduced creatine levels in the cerebellum,
pointing to the fact that creatine might have a role in ataxic disorders.
FP034
Brown-Vialetto-Van Laere Syndrome: Clinical
Course under High-Dose Riboflavin over 2 Years
Makowski C.1, Haack T.2, Prokisch H.2, Burdach S.1
1
Kinderklinik München-Schwabing, Technische Universität
München, Neuropädiatrie, München, Germany, 2Institut
für Humangenetik, Technische Universität München,
München, Germany
Case: We present the case of a now 7-year-old girl with genetically
confirmed Brown-Vialetto-Van Laere syndrome. Initial symptoms
started at 3 years of age with ataxia, chaotic eye movements, speech
arrest, and behavioral problems, later, we observed sensorineural
deafness, optic atrophy, and a facial palsy. With exome sequencing,
we found compound heterozygous missense mutations in the SLC52A2
gene which is associated with Brown-Vialetto-Van Laere syndrome.
SLC52A2 code for the human riboflavin transporter 2 (hRFT2), which is
thought to play a crucial role in brain riboflavin metabolism. Overexpression studies confirmed that the gene products of both mutant
alleles have reduced riboflavin transport activities. We started a highdose riboflavin treatment up to a maximum dose of 50 mg/kg/d with
good tolerability now over 2 years. Clinical effect was stabilization and a
better outcome in strength and fine motor skills. Conclusion: BrownVialetto-Van Laere syndrome is a potential treatable disease with the
main symptoms ataxia, optic atrophy, sensorineural deafness, and facial
palsy. Molecular testing should be performed early to because high-dose
riboflavin treatment can positively influence the course of the disease.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
FP035
Natural History of Molybdenum Cofactor
Deficiency
Mechler K.1, Mountford W.2, Hoffmann G.3, Ries M.4
1
Zentralinstitut für Seelische Gesundheit Mannheim, Klinik
für Psychiatrie und Psychotherapie des Kindes- und
Jugendalters, Mannheim, Germany, 2Premier Healthcare
Alliance, Charlotte, North Carolina, United States, 3Zentrum
für Kinder-/Jugendmedizin Heidelberg, Allgemeine
Pädiatrie, Sektion f. angeborene Stoffwechselstörungen,
Heidelberg, Germany, 4Zentrum für Kinder- und
Jugendmedizin, Neuropädiatrie, Heidelberg, Germany
Background: Molybdenum cofactor deficiency is a rare differential
diagnosis of neonatal epilepsy. Although experimental treatment
with substrate substitution was successfully performed in single cases,
the natural history of the condition including survival is still undefined.
Objectives: This article aims to quantitate the published natural history
of molybdenum cofactor deficiency. Methods: The analysis of published
cases with molybdenum cofactor deficiency was done. Descriptive
statistics were used to summarize the study population and KaplanMeier estimates were performed for median survival. Main Outcome
Measures: The main outcomes of the study were survival, cardinal
disease features at onset, and diagnostic delay. Results: The study
population included 82 patients from 49 publications including case
series and case reports. The median survival for the population was 36
months. Cardinal disease features were seizures (72%) as well as feeding
difficulties (26%) and hypotonia (11%). In addition, developmental delay
(9%), hemiplegia (2%), lens issues (2%), and hyperreflexia (1%) were
reported. The median age of onset of the disease was on the first day of
life, the median age at diagnosis was 4.5 months. The median time to
diagnosis (diagnostic delay) was 89 days. Conclusions: Molybdenum
cofactor deficiency has its onset in the neonatal period and infancy.
There is considerable diagnostic delay. Although seizures were the most
frequent cardinal sign, molybdenum cofactor deficiency should be
considered as a differential diagnosis in patients presenting with
hypotonia, developmental delay, or feeding difficulties. The survival
data will inform further natural history and therapeutic studies.
FP036
Erhebung Seltener Neurologischer
Erkrankungen im Kindesalter
Brockmann K.1
1
Klinik für Kinder- und Jugendmedizin,
Universitätsmedizin Göttingen, Sozialpädiatrisches
Zentrum, Göttingen, Germany
Recruitment of a sufficiently large cohort of patients is a prerequisite for
many research projects in the field of rare disorders. We are establishing
the Acquisition of Rare Neurological Disorders in Childhood (Erhebung
Seltener Neurologischer Erkrankungen im Kindesalter—ESNEK) which
is modeled on the German pediatric surveillance system (Erhebungseinheit seltener pädiatrischer Erkrankungen in Germany, ESPED).
ESNEK will be based in the Department of Pediatrics and Adolescent
Medicine, University Medical Center, Göttingen. Any clinical researcher
in the field of pediatric neurology in German-speaking countries may
apply for admission of a scientific study, which needs nationwide
recruitment of patients with a given rare neurological disorder. A short
summary of the study design and a consent form for the parents must be
included in the application. Approval of an ethics committee must be
obtained by the respective principal investigator. ESNEK will then send
an e-mail to some 700 pediatric neurologists in Germany asking who is
in charge of a patient with this given neurological disorder. Thus, ESNEK
does not ascertain incidences but prevalences of rare disorders. The
pediatric neurologist mails back just the number of patients he or she is
aware of, not any names or contact data. As a next step ESNEK will send a
printed summary of the study design and a printed consent form for the
parents via post, to be forwarded to the families. Parents who agree to
participate will fill in and sign the consent form and send it back to
ESNEK. These forms will be registered and forwarded to the respective
principal investigator, who now may contact the patients’ families
directly. ESNEK will prove to be a tool facilitating a wide range of
Abstracts
S13
Munich, 17th to 19th September 2014
scientific research projects in the field of rare neurologic disorders in
childhood.
Vascular Diseases and Varia
FP037
Moyamoya Angiopathy in Children: Clinical
Characteristics of 26 Patients
Introduction: Moymoya angiopathy in children is a rare and progressive
disease and an important differential diagnosis in childhood stroke.
Diagnostic delay often occurs and can lead to repetitive ischemia.
Clinical data in children are limited. Patients: We report on clinical
characteristics of 26 newly diagnosed patients who were treated in the
Moymoya Center of the Children’s Hospital, Zurich, from March 2011 to
January 2014 and were referred from across Europe. Clinical evaluation
consisted of a neurological and developmental status and the pediatric
stroke outcome score (PSOM) which up to now has been used in 17
patients. Neuroradiological evaluation included magnetic resonance
imaging (MRI) with magnetic resonance angiography (MRA), conventional angiography, and positron emission tomography (PET). Treatment plan was individualized. In 25 patients, multiple cerebral
revascularizations were performed. Results: Median age at manifestation was 4.5 years (range, 7 months-14 years). Of the 26 children, 11
were younger than 4 years at symptom onset. The woman-to-man ratio
was 1.4:1, the ratio Moyamoya disease: Moyamoya syndrome 1.6:1. Of
the 13 children, 8 older than 4 years complained about headaches,
which presented as migraine in five children. PSOM ranged from 0 to 10.
The score was 0 in five children, and we scaled values above 5 in three
toddlers. A total of 21 patients had bilateral ischemic attacks (TIAs) that
were misdiagnosed as an aura in some of the older patients. Bilateral
angiopathy was confirmed radiologically. In eight children, posterior
circulation was involved. The median age in these children was 2 years,
and by tendency they had a higher PSOM score and a more rapid disease
progression. Conclusion: In our cohort, children younger than 5 years
tended to have a more rapid disease progression with involvement of
multiple vascular territories of the anterior and posterior circulation.
Early diagnosis and surgical revascularization in this patient group is
elementary for stroke prevention. Headaches and migraine are common
symptoms in children older than 5 years. TIAs can be misinterpreted as
an aura.
FP038
Trichothiodystrophy Presenting with
Cardiomyopathy and Recurrent Stroke Episodes
Harmsen S.1, Distelmaier F.1, Frank J.2, Karenfort M.1
1
Universitätsklinikum Düsseldorf, Klinik für Allgemeine
Pädiatrie, Neonatologie und Kinderkardiologie, Düsseldorf,
Germany, 2Universitätsklinikum Düsseldorf, Hautklinik,
Düsseldorf, Germany
Background: The term trichothiodystrophy (TTD) (OMIM 601675)
refers to a rare genetic syndrome, presenting with a heterogeneous
clinical picture and variable prognosis. Main symptoms include a typical
brittle hair texture, variable photosensitivity, xerosis cutis, short stature,
and psychomotor retardation. In autosomal recessive forms, mutations
in XPB, XPD, TTDA, and TTDN1 genes are described. Case Report: Here,
we report on a 3-year-old boy, who presented with acute onset of left
hemiparesis with facial nerve palsy. In the past, developmental delay
and dilated cardiomyopathy of unknown origin were diagnosed. He was
pretreated with anticongestive drugs. Brain magnetic resonance imaging (MRI) showed acute ischemic infarction of the right middle cerebral
artery. Intravenous thrombolysis within 3 hours after onset of symptoms led to recanalization and dramatic improvement in symptoms. In
the following, low-dose aspirin treatment (2 mg/kg/d) was started for
further stroke prevention. However, on day 7, he suffered from a
prolonged focal epileptic seizure with altered consciousness. MRI was
Reference
1 Toelle SP, Valsangiacomo E, Boltshauser E. Trichothiodystrophy with
severe cardiac and neurological involvement in two sisters. Eur J
Pediatr 2001;160(12):728–731.
FP039
Late-Onset Meningitis by Group B Streptococci:
A Cause for Cerebrovascular Complications
Tibussek D.1, Yau I.2, Sinclair A.2, Jahn P.3, Mayatepek E.4,
Askalan R.2
1
Division of Neurology, Hospital for Sick Children,
University of Toronto, Toronto, Ontario, Canada, 2Hospital
for Sick Children, University of Toronto, Toronto, Canada,
3
Neonatologie, Klinik für Kinder und Jugendliche,
Leverkusen, Germany, 4Department of General Paediatrics,
Neonatology and Paediatric Cardiology, Heinrich-HeineUniversität, Düsseldorf, Germany
Background: Group B streptococcus (GBS) is a leading cause of neonatal
and infantile meningitis. Neonatal strokes have been described as a
complication of early-onset GBS meningitis. Little is known about
cerebrovascular disease related to late onset GBS meningitis. We here
describe nine patients with late onset GBS meningitis complicated by
cerebrovascular disease. Methodology: The methodology includes a
retrospective case series. All nine patients have been seen by the first
author at three different institutions. Among these, seven patients have
been seen at the Hospital for Sick Children. Patient charts were reviewed
with regard to clinical presentation, laboratory findings, treatment,
clinical course, and outcome. Cerebral imaging was reviewed with
special emphasis on stroke pattern and cerebrovascular findings.
Results: Among the nine cases, eight had an acute ischemic stroke
(AIS) accompanied by a cerebral sinovenous thrombosis (CSVT) in one.
One infant had a significant cerebral arteriopathy without an AIS,
characterized by severe stenosis of the basilar artery and both internal
carotid arteries. Ischemic lesions were either within a clearly defined
arterial territory (n ¼ 1) or characterized by multiple, bilateral, cortical,
and subcortical ischemic lesions. Computed tomographic angiography
or magnetic resonance angiography showed significant stenotic cerebral vasculopathy in four cases. Three patients were treated with anticoagulation. Outcome was good in two, severe developmental delay and
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Hackenberg A.1, Plecko B.1, Khan N.2
1
Kinderspital Zürich, Abteilung für Neuropädiatrie, Zürich,
Switzerland, 2Kinderspital Zürich, Moyamoya Center,
Abteilung für Pädiatrische Neurochirurgie, Zürich,
Switzerland
repeated and showed a filling defect in the left middle cerebral artery.
On the basis of the successful lysis during the initial episode and after
careful evaluation of contraindications, intravenous thrombolysis was
administered again. However, in this situation, he did not show any
benefit. Moreover, on day 8, he even suffered from reinfarction of his
right middle cerebral artery and additional infarction of his left posterior cerebral artery. Treatment was continued with low-molecular heparin and later switched to warfarin. Unfortunately, the subsequent
neurological outcome was unfavorable. There was no evidence of causal
thrombophilia, dyslipidemia, sickle cell disease, metabolic, or autoimmune disorder. Echocardiography showed a dilated left ventricle and a
significantly reduced- shortening fraction, while no thrombi could be
detected. However, due to the infarct morphology (cardio-) embolic
infarction was considered as probable underlying cause. Since birth, he
had suffered from dry, scaly skin, and had a striking hair texture with
brittle, short hair with patchy thinning and alopecic areas, suggesting
TTD as the underlying disease. With electron and polarization microscopy of the hair, the diagnosis TTD could be confirmed. The hair
abnormalities result from sulfur deficiency in hair matrix proteins.
Seven months after the acute episode, the boy died due to cardiac
insufficiency after severe status epilepticus. Conclusion: This is the
second documented case showing a possible association of TTD with
dilated cardiomyopathy and strokes.1 Cardiovascular events may at least
in parts account for the high mortality in patients affected with this
disease. In summary, uncommon hair structure in combination with
cardiomyopathy and stroke should lead to an investigation of TTD.
S14
Abstracts
Munich, 17th to 19th September 2014
infantile spasms in one, spastic hemiparesis and focal epilepsy in one
patient. Three cases showed mild developmental delay with secondary
microcephaly in one patient. Two cases underwent neurosurgery for
hydrocephalus and subdural hygroma, respectively. Conclusion: Lateonset GBS meningitis is a risk factor for severe cerebrovascular complications, including AIS and CSVT. The fact that all patients had been seen
within only 3 years indicate that this complication might be underreported. We will discuss possible mechanisms and the possible role of
preventive anticoagulation. We recommend a low threshold for cerebral
imaging, including vascular imaging in these cases.
Munich, 17th to 19th September 2014
FP040
Clinical and Radiological Differences between
Children and Adults with Posterior Reversible
Encephalopathy Syndrome: The Retrospective
Berlin PRES Study
Liman T.1, Bohner G.2, Siebert E.3, Endres M.4
1
Charité/Center for Stroke Research Berlin, Neurologie,
Berlin, Germany, 2Charité, Neuroradiologie, Berlin,
Germany, 3Charité- Universitätsmedizin Berlin, Zentrum
für diagnostische Radiologie und interventionelle
Radiologie, Berlin, Germany, 4Charite ‐ Universitätsmedizin
Berlin, Klinik und Poliklinik für Neurologie, Berlin, Germany
Background: Posterior reversible encephalopathy syndrome (PRES) is a
serious and increasingly recognized disorder, but data from observational studies on clinicoradiological differences between etiologies and
age groups are limited. In this study, we aimed to investigate the clinical
and imaging characteristics of PRES in children compared with adults in
a large cohort. Methods: We retrospectively reviewed the radiological
report databases between January 1999 and August 2012 for patients
with PRES. Patients fulfilling the criteria for PRES after detailed investigation of clinical charts and imaging studies were separated into
children (< 18 years) and adults (% 18 years). Various imaging features
at onset of symptoms and on follow-up as well as clinical and paraclinical data were analyzed. Results: A total of 18 pediatric and 92 adult
patients with PRES were included in the study. In pediatric PRES
patients, seizures were significantly more frequent as initial PRESrelated symptom (p < 0.02), whereas altered mental state was significantly less frequent (p ¼ 0.001). The superior frontal sulcus topographic
lesion pattern occurred as frequent as the parieto-occipital one and was
significantly more prevalent in children (36.8% vs. 16.4; p ¼ 0.02).
Moderate-to-severe edema were more frequent in adults than in
children with 44 vs. 23% (p ¼ 0.07). Blood pressure levels at PRES onset
were higher in adults (p < 0.01). Conclusion: In our PRES cohort, we
found major clinicoradiological differences between pediatric and adult
PRES patients. However, prospective studies are warranted to establish
factors that are specifically associated with pediatric PRES.
Diagnosis of Fetal Alcohol Spectrum Disorders
FP041
Landgraf M.1, Heinen F.1
1
Dr. von Haunersches Kinderspital, Universität München,
Pädiatrische Neurologie, Entwicklungsneurologie und
Sozialpädiatrie, München, Germany
Background: In Europe, up to 30% of all pregnant women consume
alcohol. Alcohol related damages of the child are summarized as fetal
alcohol spectrum disorders (FASD). The full picture fetal alcohol syndrome (FAS) is estimated to occur in 8 of 1,000 births. The patients with
FASD are in large part diagnosed wrongly for a long time and get the
right diagnosis late in childhood or even adulthood. Methods: Fetal
alcohol syndrome can be diagnosed by means of the German S3guideline. The diagnostic criteria were determined based on the evidence assessed literature and on the consensus of the multidisciplinary
guideline group (relevant professional societies, patient support group
FASD Germany, and other FAS experts). The other fetal alcohol spectrum
disorders can be diagnosed with the aid of a Canadian guideline which is
based on long-time clinical experience. The evidence of the previous
literature is not sufficient enough to give methodologically objective
evidence-based recommendations for FASD. Results: In children and
adolescents with FASD, four diagnostic columns are relevant: (1) growth
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
deficits, (2) facial characteristics, (3) abnormalities of the central
nervous system), and (4) maternal alcohol use during pregnancy. For
the diagnosis of FAS at least one deficit of growth, three defined facial
anomalies, and at least one structural or functional abnormality of the
CNS should be present. The maternal alcohol consumption does not
have to be confirmed. For the diagnosis of partial fetal alcohol syndrome
(pFAS), at least two of the three defined facial anomalies and at least
three abnormalities of the CNS as well as the confirmation of maternal
alcohol use should be existent. Alcohol-related neurodevelopmental
disorder (ARND) can be diagnosed if at least three abnormalities of the
CNS are present and intrauterine alcohol exposure is confirmed. The
diagnosis of alcohol-related birth defects should be made with caution
and always requires the confirmation of alcohol use during pregnancy.
Conclusion: The diagnosis of the fetal alcohol spectrum disorders
remains a medical and psychological challenge. Guideline recommendations facilitate the clinical diagnostic process. The impairment of
functions and everyday life can be influenced positively by early
diagnosis and individual support of the patient.
FP042
Adrenocorticotropic Insufficiency: Important
Differential Diagnosis in Neuropsychiatric
Diseases
Gebhardt B.1, Schöne S.1
1
MVZ-Gelnhausen, Neuropädiatrie, Kinder Endokrinologie,
Gelnhausen, Germany
The adrenal stress response is a neuroendocrine regulation system of
essential importance. Current clinical symptoms of its impaired function are exercise intolerance, vertigo, syncope, confused consciousness,
fatigue, mood depression, and hence neuropediatric presentations.
Because of this unspecific presentation, patients are often suspected
to have a psychiatric or dissociative disease. Patients: We report
approximately 15 patients aged 5 to 17 years presenting with earlier
mentioned symptoms, some of them with years of prehistory before
approaching neuropediatric diagnostic work-up. Besides this, all of
them received a stepwise testing of the adrenocorticotropic axis using
a low dose adrenocorticotropic hormone—stimulation test und further
stimulation tests if necessary. Results: Pf the 15 patients, 5 patients
suffered from adrenal insufficiency, 3 with increased adrenal antibodies,
1 with X-ALD, and 1 unclear. The other 10 patients showed pituitary or
hypothalamic malfunction, 7 unclear, 1 craniopharyngeoma, 1 prolactinoma, and 1 hypothalamic lipoma. One girl with autoimmune adrenal
insufficiency also suffered from temporal lobe epilepsy. Of the 15
patients, 2 patients demonstrated with depressive symptoms. The
two pituitary tumor patients also had additive hormonal impairments.
Therapeutic substitution with hydrocortisone or dexamethasone led to
clinical improvement in all patients. Discussion: Disturbed stress regulation often leads to unspecific symptoms overlapping the field of
neuropediatric and psychogenic differential diagnosis. Basal diagnostic
work-up using low dose ACTH testing regularly identifies patients with
endocrine disease and should be part of the diagnostic protocol.
FP043
Attention Deficit in Neurofibromatosis Type 1:
Part of the Neurocognitive Profile or
Comorbidity?
Schulze M.1, Granström S.2, Mautner V.2, Lidzba K.1
1
Universitätsklinik für Kinder- und Jugendmedizin
Tübingen, Neuropädiatrie, Entwicklungsneurologie,
Sozialpädiatrie, Tübingen, Germany, 2Universitätsklinikum
Hamburg-Eppendorf, Neurofibromatose-Ambulanz,
Hamburg, Germany
Background: Attention deficit disorder with and without hyperactivity
(AD(H)D) is one of the most common behavioral and neurocognitive
complications in neurofibromatosis type 1 (NF1). Previous research
reports a prevalence of AD(H)D up to 50% in the NF1 population. Given
the high prevalence and the fact that AD(H)D has a significantly higher
incidence in children with NF1 than in their siblings or parents without
NF1, an independent comorbidity seems improbable. Current data on
the etiology of AD(H)D in NF1 are still inconclusive, but there is evidence
Abstracts
S15
Munich, 17th to 19th September 2014
FP044
Unidentified Bright Objects in the Internal
Capsule in Neurofibromatosis Type 1:
Microstructural Changes and Their Relationship
to Fiber Tracts
Groeschel S.1, Wilke M.1, Mautner V.2, Bender B.3, KrägelohMann I.1, Haas-Lude K.1
1
Universitätsklinikum Tübingen, Neuropädiatrie,
Entwicklungsneurologie, Sozialpädiatrie, Tübingen,
Germany, 2Universitätsklinikum Hamburg-Eppendorf,
Neurofibromatose-Ambulanz, Hamburg, Germany,
3
Universitätsklinikum Tübingen, Abteilung Diagnostische
und Interventionelle Neuroradiologie, Tübingen, Germany
Objective: In children with neurofibromatosis type 1 (NF1), the most
common intracranial lesions are foci with signal hyperintensity in T2weighted magnetic resonance (MR) images. These focal signal abnormalities are often described as an unidentified bright object (UBO), as
only little is known about their nature. Diffusion-weighted imaging
allows the in vivo characterization of tissue microstructure and can
visualize fiber tracts. The aim of this work is to further characterize the
microstructure of UBOs in the internal capsule and their relationship
with fiber tracts. Method: Three children with NF1 and UBOs in the
internal capsule (6, 13 and 16 years of age) and a typically developing
child (16 years of age) were investigated using diffusion-weighted MRI
with a high angular resolution sequence on a 1.5 T Siemens Avanto. In
addition to assessment of diffusion tensor parameters and fiber orientation distribution (FOD) in the UBO and the corresponding contralateral side, probabilistic fiber tracking was performed for generating
the cortico-spinal tract and anterior thalamic radiation. Results: Two
patients showed UBOs unilateral at identical locations in the knee of the
internal capsule, in one patient the UBOs were bilateral. Compared with
the normal appearing side and to the healthy control, the UBO showed
significantly different diffusion parameters with higher mean and axial
diffusivity, lower fractional anisotropy. In addition, visual analysis of the
FOD amplitude showed decreased fiber density in the UBO as well as in
the anterior part of the thalamus. MR tractography revealed that
corticospinal fibers traversed the internal capsule in the middle of the
posterior limb, both in the patients and the control. Fibers passing
through the UBO appeared less dense and mildly shifted. Patients had no
corresponding neurological deficit. Conclusion: These results of ad-
vanced diffusion imaging analyses indicate that UBOs consist of reduced
fiber density of fibers passing through them, but still remaining pathways, accordingly without loss of neurological function.
Visual Diagnosis: Costello Syndrome
FP045
Kurlemann G.1, Althaus J.2, Schwartz O.3, Elpers C.4,
Fiedler B.2
1
Klinik für Kinder und Jugendmedizin, Allgemeine
Pädiatrie, UKM, Neuropädiatrie, Münster, Germany, 2Klinik
für Kinder- und Jugendmedizin, Universitätsklinikum
Münster, Allgemeine Pädiatrie, Bereich Neuropädiatrie,
Münster, Germany, 3Klinik für Kinder und Jugendmedizin,
Allgemeine Pädiatrie, Neuropädiatrie, Münster, Germany,
4
Klinik für Kinder- und Jugendmedizin, Allgemeine
Kinderheilkunde, UKM, Neuropädiatrie, Münster, Germany
Costello syndrome is rare, it is thought likely that there is a high number
of unreported cases. To date, just more than 200 people with Costello
syndrome have been described in the literature. It is characterized by
mutations in the HRAS gene and belongs to the clinically defined group
of RASopathies with an increased risk of malignant tumorous diseases in
early childhood, for example, bladder carcinoma, neuroblastoma, rhabdomyosarcoma, perioral and anal papillomas, and vestibular schwannomas. Screening examinations of these children at regular intervals are
therefore vital, particularly to classify the symptoms. Clinical symptoms
such as muscular hypotonia, feeding difficulties, cardiomyopathy, macrocephaly, cognitive deficits, fleshy, damp hands and feet, curly hair, and
ulnar deviation of the hands are indicatory. We report on the clinical
course and molecular genetic findings in a 13-year-old girl, showing
pictures of the typical clinical features which enable an accurate
syndromatic classification and thus systematic recognition of the condition. Only in this way can the specified screening examinations be
used selectively to improve the prognosis regarding increased tumor
risk.
Plenary Session
FP046
Brain Morphometry in Pontocerebellar
Hypoplasia Type 2
Groeschel S.1, Ekert K.1, Sánchez Albisua I.1, Frölich S.1,
Krägeloh-Mann I.1
1
Universitätsklinikum Tübingen, Neuropädiatrie,
Entwicklungsneurologie, Sozialpädiatrie, Tübingen,
Germany
Objective: Pontocerebellar hypoplasia type 2 (PCH2) is caused by a
defect in the TSEN54 gene and leads to severe and early disruption of
brain development, especially of cerebellum and pons. The aim of this
article was to quantify the growth of several brain structures during
brain development in children with PCH2. Methods: A total of 32
magnetic resonance images (MRI) of 24 children with PCH2 (age range,
0.02-17 years.) were analyzed volumetrically and compared with
images of 34 typically developing children (age range, 0.02-17 years.)
with similar age and gender distribution (derived from National Institutes of Health MRI study of normal brain development). All children
with PCH2 had the p.A307S mutation in the TSEN54 gene. Images of the
children with PCH2 were available either on film (n ¼ 12) or in digital
format (n ¼ 20). To quantify all images volumetrically, images on film
were digitalized. First, manual brain masks were generated and then
semi-automatically adjusted further using intensity thresholds. Volumes of cerebellum, brain stem, and area of pons, as well as cerebral
volume and volume of frontal lobes were measured. For validation of the
method part of the digital images of patients and controls were
processed as images on film. Furthermore, intra- and inter-rater variability was tested. Results: Children with PCH2 showed the reduced
volume of all measured brain structures compared with healthy controls. The difference was largest in volumes of cerebellum, pons, and
brain stem. In postnatal development, infratentorial structures increased only little in size, and this reduced growth was also seen in
the longitudinal measures of four patients. Also, the supratentorial brain
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
suggesting that attention deficit might be part of the neurocognitive
profile of NF1. In our study, we aimed at obtaining specific neuropsychological profiles of patients with NF1 plus AD(H)D as compared with
patients with idiopathic AD(H)D. Methods: Standardized neuropsychological assessments were performed in 43 children and adolescents with
NF1 plus AD(H)D or idiopathic AD(H)D, aged between 6 and 11 years.
We examined intelligence (Wechsler Intelligence Scale for Children IV),
attention functions (Test of Variables of Attention [TOVA]), and behavioral ratings on AD(H)D symptoms (Conners 3). Observed frequencies of
subnormal performance were compared with the expected frequency
(from normative sample) by nonparametric chi-square tests. Results:
There were no significant differences between the patient groups in fullscale intelligence quotient (mean, 91.05; standard deviation [SD], 11.4),
age (mean age, 8.56 years; SD, 1.4), and sex (26 males and 17 females).
For both the groups, subnormal performance was significantly more
frequent for response time and omission errors in the TOVA (implying
increased inattention), as well as the Conners 3 subscales inattention,
hyperactivity/impulsivity, learning problems, executive functions, and
peer relations. Specific deficits of the NF1 sample were identified for
variability of response times in the TOVA (37.0%) and commission errors
in the first half of the TOVA (25.9%). Together with an extremely high
frequency of increased omission errors (51.9%), these results indicate
that NF1 patients are specifically impaired in sustained attention and
adaptation to test requirements. In addition, the NF1 sample showed a
significantly increased probability of clinically relevant aggressive behavior (42.3%). Conclusion: Against a common set of attention problems,
specific attention functions seem to differ between patients with NF1
plus AD(H)D and patients with idiopathic AD(H)D. Thus, attention
deficit in NF1 might not be an independent comorbidity, but part of a
specific neurocognitive profile of NF1.
S16
Abstracts
Munich, 17th to 19th September 2014
Munich, 17th to 19th September 2014
volume showed reduced growth compared with the healthy controls,
the frontal lobe was not affected predominantly. Validation of the
method showed a high precision and reproducibility, also in measurements on film. Conclusions: In a genetically very homogenous group of
children with PCH2, standardized volumetric data were presented and
compared with healthy controls. In addition to the infratentorial brain
structures, also the supratentorial brain growth was reduced. Two
mechanisms might contribute to this; on the one hand, a severe
disruption of the cerebellar-cerebral networks caused by a primary
cerebellar dysfunction, and on the other hand a postnatal
neurodegeneration.
FP047
The Relevance of Vitamin B6 Plasma Profiles in
the Diagnostic Work-up of Early Infantile
Epileptic Encephalopathies
Plecko B.1, Abela L.1, Bürer C.2, Wohlrab G.3, Schmitt B.3,
Steinlin M.4, Hersberger M.5, Mathis D.5
1
Universitäts-Kinderspital Zürich, Neurologie, Zürich,
Switzerland, 2Universitäts-Kinderspital Zürich,
Stoffwechsel und molekulare Pädiatrie, Zürich, Switzerland,
3
Universitäts-Kinderspital Zürich, Neurologie/
Elektrophysiologie und Anfallssprechstunde, Zürich,
Switzerland, 4Universitätsklinik für Kinderheilkunde,
Inselspital Bern, Bern, Switzerland, 5UniversitätsKinderspital Zürich, Klinische Chemie und Biochemie,
Zürich, Switzerland
Background: To date, we know of five inborn errors of metabolism, that
manifest with vitamin B6 responsive seizures. These defects lead to
cerebral or systemic deficiency of pyridoxal 5′-phosphate (PLP) via
reduced synthesis or secondary inactivation of PLP and therapy-resistant seizures. Thereby, the vitamin B6 profile in plasma can provide
important information and be helpful in the therapeutic monitoring.
Methods: In our laboratory, we have established a sensitive Liquid
Chromatography-Mass Spectrometry-Mass Spectrometry (LC-MS-MS)
method for the analysis of all vitamin B6 vitamers (PLP, pyridoxal (PL),
pyridoxamine (PM), pyridoxine, and pyridoxic acid (PA) in different
body fluids. We analyzed the plasma samples of 4 patients with
molecularly proven antiquitin deficiency, 1 patient with phosphate
oxidase (PNPO) deficiency, both under high dose pyridoxine therapy,
and samples of 50 patients with epileptic encephalopathy of unclear
etiology, 2 of whom were on high-dose pyridoxine therapy. In each case,
1.5 mL of ethylenediamine tetra-acetic acid blood was drawn at our
clinic, immediately light protected, centrifuged within 30 minutes and
stored at #80 degrees until analysis. Results: Patients with antiquitin
deficiency did not show a specific vitamer profile, aside from very high
absolute concentrations of PLP, PL, and PA. In contrast, the single patient
with PNPO deficiency had a clearly distinct vitamer profile with elevated
PM. Of the 50 patients with epileptic encephalopathy of unclear etiology, none had decreased PLP levels, despite multidrug therapy in the
majority of patients. The two patients on high-dose pyridoxine therapy
had profiles that were indistinguishable from antiquitin deficiency.
Conclusions: Our findings confirm preliminary observations that the
plasma B6 vitamer profile may be a diagnostic clue to PNPO deficiency,
which otherwise lacks a specific biomarker. For antiquitin deficiency
measurement of α-aminoadipic semialdehyde and pipecolic acid remain reliable biomarkers. In contrast to findings in adults, our cohort of
pediatric epilepsy patients had normal plasma PLP concentrations.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Inflammatory Disorders
FP048
Clinical and Radiological Features of Children
with MOG-positive and MOG-negative ADEM
Bauman M.1, Sahin K.1, Lechner C.1, Hennes E.1, Schanda K.2,
Karenfort M.3, Koch J.4, Selch C.5, Häusler M.6, Kraus V.7,
Mader S.2, Salandin M.8, Gruber-Sedlmeyer U.9, Piepkorn
M.10, Blaschek A.11, Eisenköbl A.12, Leiz S.13, Finsterwalder
J.14, Berger T.2, Reindl M.2, Rostasy K.1
1
Medizinische Universität Innsbruck, Pädiatrie 1,
Neuropädiatrie, Innsbruck, Austria, 2Medizinische
Universität Innsbruck, Abteilung für Neurologie, Innsbruck,
Austria, 3Heinrich Heine Universität, Klinik für Allgemeine
Pädiatrie, Düsseldorf, Germany, 4Universitätskinderklinik
Salzburg, Kinderklinik, Salzburg, Austria, 5Schön Klinik
Vogtareuth, Klinik für Neuropädiatrie und Neurologische
Rehabilitation, Tagesklinik für Neuropädiatrie, Vogtareuth,
Germany, 6Universitätsklinikum Aachen, Klinik für Kinderund Jugendmedizin, Neuropädiatrie, Aachen, Germany,
7
Technische Universität München, Kinderklinik Schwabing,
München, Germany, 8Kinderklinik, Bozen, Bozen, Italien,
9
Universitäts-Klinik für Kinder- und Jugendheilkunde,
Ambulanz für Neuropädiatrie und angeborene
Stoffwechselerkrankungen, Graz, Austria,
10
Kinderkrankenhaus Auf der Bult, Neuropädiatrie,
Hannover, Germany, 11Haunersches Kinderspital,
Neuropädiatrie, München, Germany, 12Landes-Frauen-und
Kinderklinik Linz, Linz, Austria, 13Klinikum Dritter Orden,
Klinik für Kinder- und Jugendmedizin, München, Germany,
14
Klinikum Mutterhaus der Borromäerinnen, Trier,
Abteilung für Kinderheilkunde, Trier, Germany
Background: Serum myelin oligodendrocyte glycoprotein (MOG) immunoglobulin (IgG) antibodies have recently been detected in pediatric
acute disseminating encephalomyelitis (ADEM). Aim: This article aims
to further delineate the clinical and neuroradiological features of
pediatric ADEM with serum antibodies against MOG. Methods: A total
of 39 pediatric patients with an episode of ADEM were recruited. The
following outcome measures were obtained: clinical features, intrathecal IgG-synthesis, MRI findings and outcome. Cell-based immunofluorescence assay was used to measure serum IgG antibodies to MOG.
Results: All 39 children fulfilled the clinical criteria of ADEM. The cohort
consisted of 17 girls and 22 boys with a median age of 5 years (range, 117 years). On the basis of the presence of different magnetic resonance
imaging (MRI) features the cohort was divided into two groups: children
with an MRI characterized by large, hazy, bilateral, and widespread
lesions (n ¼ 28) and children with at least two atypical MRI features in
addition (e.g., unilateral lesions only and not widespread). Children from
the first group presented at a younger age (median, 5 years; range, 1-17
years vs. median, 9 years range, 1-14 years; p ¼ 0.037), had a higher
cerebrospinal fluid cell count (p ¼ 0.004) and a better clinical outcome (p
¼ 0.003). In addition, lesions were detected in more anatomical areas
when compared with children from the second group (p ¼ 0.001) often
combined with a resolution of signal changes (p < 0.001). Overall, six
children with atypical MRI findings were assigned an alternative
diagnosis on follow-up. Serum MOG-IgG antibodies (median, 1:2,560;
range, 1:160-1:20,480) were detected in 19 children all of whom had an
MRI characterized by large, bilateral, and widespread MRI lesions. In 16
of 18 children with follow-up samples, titers declined over time (p <
0.001). On the basis of MOG status, this subgroup was further divided
and analyzed. Apart from the observation that children with MOG
antibodies had more often involvement of the myelon characterized
by a longitudinally extensive transverse myelitis (LETM) (p ¼ 0.039),
children with a typical MRI had similar clinical features and clinical
outcome. Conclusion: The majority of children with ADEM and an MRI
revealing hazy, bilateral, and widespread lesions had MOG antibodies
declining overtime. They often have a LETM and resolution of white
matter lesions combined with a favorable clinical outcome. Children
with ADEM, atypical MRI features, and absent MOG antibodies have a
high likelihood of an alternative diagnosis.
Abstracts
S17
Munich, 17th to 19th September 2014
FP049
MOG- and AQP-4-IgG Antibodies in Children
with Neuromyelitis Optica Spectrum Disorders
and NMO-Related Symptoms
Background: Neuromyelitis optica (NMO) is characterized by episodes
of recurrent or bilateral optic neuritis (ON) and longitudinally extensive
transverse myelitis (LETM). Particularly in adults, aquaporin-4-antibodies (AQP-4-Abs) are found in the serum in up to 80% of all the cases.
Some patients do not fulfill all criteria initially and present only with a
recurrent ON, bilateral ON, or LETM with AQP-4-Abs. These cases belong
to the NMO Spectrum Disorders (NMOSD). Recently, it was shown that
children with AQP-4-Ab negative NMOSD can have myelin oligodendrocyte glycoprotein antibodies (MOG-Abs). Objectives: Frequency of
MOG- and AQP-4-IgG antibodies in children with NMO, recurrent ON,
bilateral ON, or LETM. Methods: Children with NMO, recurrent ON,
bilateral ON, or LETM were included in the study. The following
parameters were studied: age, sex, CSF cell count, presence of oligoclonal bands, serum MOG-, and AQP-4-Ab status. Results: A total of 35
children were included. Of the 35 children, 13 fulfilled the criteria of
NMO (four males and nine females), 11 of 35 had an LETM (six males and
five females), 7 of 35 recurrent ON (one male and six females), and 4 of
35 bilateral ON (three males and one female). In 6 of 35 children (five
NMO and one LETM) AQP-4-Abs were detected (median, 1:320; range,
1:160 to 1:1,280). Of the 35 patients, 16 (five NMO, four LETM, four
recurrent ON, and three bilateral ON; nine males and seven females) had
MOG-Abs (median, 1:1,280; range, 1:160-1:5,120). Neither AQP-4- nor
MOG-Abs were found in 13 of 35 patients (37%). In none of the children
both antibodies were detected at the same time. Children with AQP-4Abs were older (median, 12 years; range, 8-14 years) than children with
MOG-Abs (median, 6 years; range, 4-15 years). However, no differences
were found in the frequency of intrathecal IgG synthesis-present only in
three children-or in the male-to-female ratio. Conclusion: Of the 35
children with NMOSD and NMO-related symptoms, only 6 children had
AQP-4-Abs. On the contrary, MOG-Abs were found in 16 of 35 children.
We therefore recommend to evaluate the MOG-Abs status at initial
manifestation, because of the diagnostic and possible therapeutic
implications.
FP050
Bigi S.1, Sickand M.2, Twilt M.3, Sheikh S.2, Dropol A.2,
Benseler S.4
1
Division of Neurology, The Hospital for Sick Children,
Toronto, Canada, 2Division of Rheumatology, The Hospital
for Sick Children, Toronto, Canada, 3Division of
Rheumatology, Aarhus University Hospital, Aarhus,
Dänemark, 4Division of Rheumatology, Section Chief,
Department of Pediatrics, Alberta Children’s Hospital,
Calgary, Canada
Background: Antibody-mediated inflammatory brain diseases (Ab-mediated IBrainD) are devastating diseases affecting previously healthy
children and resulting in severe neurological sequelae when untreated.
The spectrum of Ab-mediated IBrainD is constantly expanding, jeopardizing early recognition, and rapid initiation of targeted treatment.
Aims: This article aims to (1) describe the clinical spectrum of childhood
Ab-mediated IBrainD entities, (2)review the diagnostic evaluation and
current management, and (3) assess the neurological outcome at the last
follow-up. Methods: A single-center cohort study of consecutive patients aged & 18 years diagnosed with an AB-mediated IBrainD at a
tertiary pediatric care center was performed, between January 2005 and
July 2013. Standardized clinical data, laboratory test results, neuroimaging features, as well as treatment regimens were captured. Primary
outcome was the neurological deficit at last follow-up measured by the
pediatric stroke outcome measure. Results: During the study period, our
center enrolled a total of 169 children with IBrainD into “BrainWorks”;
20 (12%) of whom were diagnosed with an AB-mediated IBrainD. The
median age at presentation was 12.1 years (range, 3.1-17.1 years), 14
(70%) were females. Diagnoses: Overall, eight (40%) patients had neuromyelitis optica (NMO) or anti-NMDA-receptor encephalitis respectively,
two Hashimoto encephalitis, one glutamic acid decarboxylase (GAD)
encephalitis, and one AB-mediated cerebellitis. All children presented
with focal neurological deficits, 11 (55%) had seizures including all
patients with anti-NMDA-receptor encephalitis, Hashimoto encephalitis and GAD encephalitis; six patients (30%) required intensive care unit
admission. Antibodies were detected in serum in all patients. Patients
with NMO and anti-NMDA-receptor encephalitis showed an increased
cell count in the CSF, mean 19.8 (standard deviation [SD] 22.7) and 32.4
(SD 23.9), respectively. Median time from symptom onset to diagnosis
was 47 days (range, 6-741 days). All patients received a B-cell targeted
therapy according to the “BrainWorks” protocol. One child with antiNMDA-receptor encephalitis died during the acute clinical course due to
a complication of an intervention and multiorgan failure. At the last
follow-up (median follow-up time, 1.3 years [range, 0.7-5.7 years]), 30%
of the children had moderate or severe neurological sequelae.
Conclusions: Children with Ab-mediated IBrainD represent a significant
proportion amongst the IBrainD. Seizures at presentation together with
focal neurological deficits are the hallmark of anti-NMDA-receptor
encephalitis. One of the three children had residual neurological deficits
interfering with daily life activities.
FP051
Presentation of an Anti-NMDAR-Encephalitis
with Focal Motor Seizures and Focal Movement
Disorder
Berger A.1, Schmid L.2, Betzler C.3, Bien C.4, Rostasy K.5,
Makowski C.6
1
Klinikum Harlaching und Klinikum Weiden,
Neuropädiatrie, München, Germany, 2Klinikum
Harlaching, Kinderklinik, München, Germany, 3Clinic for
Neuropediatrics and Neurorehabilitation, Schön Clinic,
Vogtareuth, Germany, 4Krankenhaus Mara, EpilepsieZentrum Bethel, Bielefeld, Germany, 5Department für
Kinder- und Jugendheilkunde I, Medizinische Universität
Innsbruck, Neuropädiatrie, Innsbruck, Austria, 6Klinikum
Schwabing, Abteilung Neuropädiatrie, München, Germany
Objective: This article aims to compare the clinical features of an
uncommon manifestation of an anti-N-methyl d-aspartate (NMDAR)
antibody encephalitis with other reported cases Method: A case report
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Lechner C.1, Baumann M.1, Schanda K.2, Blaschek A.3, Lücke
T.4, Klein A.5, Leiz S.6, Gruber-Sedlmayr U.7, Brunner-Krainz
M.7, Pritsch M.8, Koch J.9, Schimmel M.10, Häusler M.11,
Karenfort M.12, Reindl M.2, Rostasy K.1
1
Medizinische Universität Innsbruck, Department für
Kinder- und Jugendheilkunde I, Division Neuropädiatrie,
Innsbruck, Austria, 2Medizinische Universität Innsbruck,
Abteilung für Neurologie, Innsbruck, Austria, 3Dr. von
Haunersches Kinderspital, Pädiatrische Neurologie und
Entwicklungsneurologie, München, Germany, 4Klinik für
Kinder- und Jugendmedizin der Ruhr-Universität Bochum,
Neuropädiatrie mit Sozialpädiatrie, Bochum, Germany,
5
Universitäts-Kinderspital Zürich, Neuropädiatrie, Zürich,
Switzerland, 6Klinikum Dritter Orden, Klinik für Kinderund Jugendmedizin, München, Germany,
7
Universitätsklinik für Kinder- und Jugendheikunde Graz,
Allgemeine Pädiatrie, Graz, Austria, 8DRK-Kinderklinik
Siegen, Neuropädiatrie, Siegen, Germany,
9
Universitätskinderklinik Salzburg, Kinderklinik, Salzburg,
Austria, 10Klinik für Kinder und Jugendliche, Klinikum
Augsburg, Neuropädiatrie, Augsburg, Germany,
11
Universitätsklinikum Aachen, Klinik für Kinder- und
Jugendmedizin, Neuropädiatrie, Aachen, Germany,
12
Heinrich Heine Universität, Klinik für Allgemeine
Pädiatrie, Düsseldorf, Germany
Recognition of Antibody-Mediated
Inflammatory Brain Diseases in Children
S18
Abstracts
Munich, 17th to 19th September 2014
Munich, 17th to 19th September 2014
of a 2 + 7/12-year-old girl Result: We report a case of a 2 + 7/12 years old
girl who presented with series of right focal tonic seizures without
alteration of consciousness, later on following isolated perioral twisting
and dyskinesia of the right hand without impaired consciousness. No
additional symptoms of an anti-NMDAR-encephalitis appeared. Initial
electroencephalograms (EEGs) were normal, developing a continuous
deceleration of the left hemisphere within 3 weeks. Cerebral magnetic
resonance imaging and cerebrospinal fluid (CSF) were normal. NMDAR
antibodies were highly positive with 1:2,000 in serum, 1:64 in CSF. We
gave three pulses of intravenous methylprednisolone within 3 months.
Last follow-up 3/13 with good outcome and decreased NMDAR antibody
titers. The EEG still showed a discrete intermittend deceleration, the
right hand still showed a discrete athetosis. Neoplasm screening was
negative. Interpretation: 1. The age of onset of an anti-NMDAR antibody
encephalitis can be very early in childhood (40% of patients in literature
are younger than 18 years, the youngest reported patient is 23 months
old). 2. Psychological/mental alterations can be absent (although 87.5%
of patients in the literature start with psychiatric alterations). 3. The
symptoms of an anti-NMDAR antibody encephalitis such as movement
disorders and motor seizures can be localized strictly unilateral-similar
to Rasmussen encephalitis (so far reported in one 11 years old girl with
anti-NMDAR antibody encephalitis). 4. The treatment of anti-NMDAR
antibody encephalitis spans a longer unproved period of time. Rarely,
monotherapy with intravenous methylprednisolone is sufficient—often
an add-on therapy with rituximab is necessary. Currently, there does not
exist any standard for childhood and adolescence treatment.
FP052
Severe Anti-NMDAR-Encephalitis with Extreme
Movement Disorder in an 18-Month-Old Girl:
Long-Term Follow-Up by Video
Reihle C.1, Bien C.2, Severien C.3, Marquard K.4, Blankenburg
M.5
1
Klinikum Stuttgart Olgahospital, Pädiatrie 1 ‐ Pädiatrische
Neurologie, Psychosomatik und Schmerztherapie, Stuttgart,
Germany, 2Krankenhaus Mara, Epilepsie-Zentrum Bethel,
Bielefeld, Germany, 3Klinik für Kinder- und Jugendmedizin
Böblingen, Böblingen, Germany, 4Klinikum Stuttgart
Olgahospital, Pädiatrie 1 ‐ Pädiatrische Neurologie,
Psychosomatik und Schmerztherapie, Stuttgart, Germany,
5
Klinikum Stuttgart, Pädiatrie 1 ‐ Pädiatrische Neurologie,
Psychosomatik und Schmerztherapie, Stuttgart, Germany
Introduction: If anti-N-methyl d-aspartate (NMDAR) encephalitis
presents in infancy, it usually shows a clinical picture of severe acute
encephalopathy with movement disorder. We documented the followup on a case of early-childhood anti-NMDAR-encephalitis with a relapse
under second-line immunotherapy, using repeat videos. The girl improved only after an additional intensive therapy. Case Report: An 18month-old girl of nonconsanguineous descent originating from Ghana
developed a febrile encephalopathy with extreme orofacial dyskinesia
with chorea, seizures, and an extreme sleep disorder. Cerebral magnetic
resonance imaging was normal. Cerebrospinal fluid examination revealed a slight pleocytosis (18 cells/µL). High titers of NMDAR antibodies
were detected in serum (titer 1:8,000; cerebrospinal fluid not examined). An infectious encephalitis (e.g., herpesvirus) and a tumor were
excluded. First-line therapy of anti-NMDAR-encephalitis (steroid pulses,
immunoglobulins, and plasmapheresis) did not show sustained effect.
Second-line therapy (rituximab and steroid pulses) was likewise unsuccessful. Only under intensified relapse therapy (repeat plasmapheresis,
monthly endoxan plus daily low-dose steroids) was continuous improvement achieved. Mental retardation, however, became obvious at 3
years of age. Discussion: Only a few cases of anti-NMDAR encephalitis
have been described in children younger than 2 years of age. Symptoms
of an acute encephalopathy with orofacial dyskinesia and extreme sleep
disorder are clues to the diagnosis. First-line therapy and second-line
therapy are derived from adult treatment protocols, and thus far, no
standardized protocols for children have been established. In summary:
Our case suggests it may be possible to improve the outcome of infantile
anti-NMDAR encephalitis by intensification of immunotherapy, despite
the prolonged disease course. Standardization of treatment protocols for
children through clinical trials is desirable.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
FP053
The Effect of Age on Efficacy of Fingolimod
Treatment: Young Adult Patients with Multiple
Sclerosis Demonstrate Higher Relative
Reduction of Relapse Rates
Vormfelde S.1, Chitnis T.2, Karlsson G.3, Häring D.3, Ghezzi
A.4, Pohl D.5, Putzki N.3, Fuchs A.1, Gärtner J.6
1
Novartis Pharma GmbH, Nürnberg, Germany,
2
Massachusetts General Hospital, Partners Pediatric
Multiple Sclerosis Centre, Boston, United States, 3Novartis
Pharma AG, Basel, Switzerland, 4Centro Studi Sclerosi
Multipla, Gallarate, Italien, 5Children’s Hospital of Eastern
Ontario, Ottawa, Germany, 6Universitätsmedizin
Göttingen, Neuropädiatrie, Göttingen, Germany
Background: No controlled clinical study has been reported on the
treatment of children and adolescents with multiple sclerosis (MS). The
PARADIGMS study compares fingolimod orally with interferon β-1a
intramuscular in children and adolescent MS patients. To ascertain the
sample size estimation for PARADIGMS, we evaluated the relation of age
and annual relapse rate (ARR) in young adult patients with MS. These
had taken fingolimod 0.5 mg, placebo, or intramuscular interferon β-1a
in three phase III studies. Methods: Post hoc analysis of the intentionto-treat populations of three phase III studies on fingolimod: FREEDOMS, FREEDOMS II (2-year studies vs. placebo) and TRANSFORMS (1year study vs. interferon β-1a intramuscular). ARR was estimated at the
age 20 and 30 years by means of negative logistic regression adjusted for
treatment, age at randomization, and treatment-age interaction.
Results: Of all patients in FREEDOMS, FREEDOMS II, and TRANSFORMS,
at the beginning of the study 28 of 1,272 (2.2%), 17 of 1,083 (1.6%), and
40/1,292 (3.1%) were maximally 20 years old; 325 of 1,272 (25.6%), 150
of 1,083 (13.9%), and 355 of 1,292 (27.5%) were maximally 30 years old.
MS had lasted on average 2.8 to 5.2 years. The mean number of relapses
was 1.5 to 1.7 relapses in the year before study participation. In the
fingolimod 0.5 mg groups, the estimated ARRs at 20 years/30 years/
overall were: FREEDOMS 0.16/0.19/0.18, FREEDOMS II 0.27/0.24/0.21,
and TRANSFORMS: 0.14/0.17/0.16. In the control groups, the ARRs were:
FREEDOMS (Placebo): 0.73/0.57/0.40, FREEDOMS II (Placebo): 0.67/
0.51/0.40 and TRANSFORMS (interferon β-1a): 0.60/0.48/0.33. The
estimated relative ARR reduction at 20 years/30 years/overall in the
fingolimod 0.5 mg groups was: FREEDOMS (vs. Placebo): 79/67/54%,
FREEDOMS II (vs. Placebo): 59/53/48%, and TRANSFORMS (vs. interferon
β-1a): 77/64/52% (all p < 0.001). Conclusion: The relapse rate was ageindependently low with fingolimod 0.5 mg. In contrast, the relapse rate
in the control groups was higher in young adult patients than in adult
patients overall. The relative treatment effect or fingolimod 0.5 mg
compared with the controls was thus consistently stronger in young
adult patients compared with the overall populations. These results
ascertain the sample size estimation (n ¼ 190 to detect a 50% reduction
in the relapse rate of fingolimod compared with interferon β-1a) for the
study on fingolimod in children and adolescent MS patients (PARADIGMS study), which is currently recruiting worldwide.
Difficulties Diagnosing Multiple Sclerosis
FP054
Blaschek A.1, Makowski C.2, Stadelmann-Nessler C.3,
Müller-Felber W.1, Heinen F.1
1
Dr. von Haunersches Kinderspital, Pädiatrische Neurologie
und Entwicklungsneurologie, München, Germany,
2
Kinderklinik München-Schwabing, Technische Universität
München, Neuropädiatrie, München, Germany,
3
Universitätsmedizin Göttingen, Neuropathologie,
Göttingen, Germany
Aim: We present two teenagers in whom initial magnetic resonance
imaging (MRI) made diagnosis of multiple sclerosis difficult. Methods/
Results: First patient presented with multiple relapses within a couple
months leading to a substantial neurologic and cognitive deficit. Initial
MRI showed multiple large lesions with a ring-like contrast enhancement. Diagnosis was made finally via brain biopsy of one lesion. In
patient, two initial MRI together with serological markers led to the
potential diagnosis of a neurocysticercosis, which was treated and
resulted in a rapid clinical and MRI improvement. Few months later,
Abstracts
S19
Munich, 17th to 19th September 2014
patient had a new relapse with optic neuritis and now diagnosis of
multiple sclerosis was established. Conclusion: Despite clear diagnostic
criteria, the diagnosis of multiple sclerosis can be difficult. Especially in
childhood, differential diagnostic work-up is broad, and there must be
no better explanation of findings before diagnosing multiple sclerosis.
FP055
Cognitive Profile of Patients with Early Onset
Multiple Sclerosis: First Results of the
MUSICA DO Study
Introduction: Cognitive deficits and psychoaffective disturbances can
be diagnosed in the early stage of childhood multiple sclerosis (MS).
However, there is little information about the extent of MS-associated
cognitive disabilities and the impact of academic achievement and social
relationships at this age as this has not been investigated in large studies.
Method: The aim of this study was to develop a standardized screening
tool to evaluate the impact of pediatric-onset MS on cognition, mental
health, and academic achievement. In the MUSIC ADO study (Multiple
Sclerosis Inventory of Cognition for ADOlescence) an already existing
and child and adolescent-adapted screening tool was validated with
clinicometric methods. Additional questionnaires for depression, fatigue, and quality of life were added. In this prospective and multicenter
study, patients with MS and healthy controls at the age of 12 to 18 years
were included. Controls were matched for age, gender, and education.
Results: Since May 2012, a total of 104 patients with MS and 125 healthy
controls were enrolled at 30 sites in Germany and Austria and were seen
by a psychologist. Socio democratic data, a full-scale intelligence scale
quotient (IQ) and information on attention, visual perceptual abilities,
executive functions, verbal sculls, quality of life, depression, and fatigue
will be presented and a neuropsychological profile will be established in
patients with early onset MS. Conclusion: MUSIC ADO is the first
prospective study that investigates cognitive functioning in childhood
MS in a large study group and compares it to controls. It presents a
screening tool that can easily be used in the clinical routine.
FP056
A New Computed Tool Detects Subtle
Differences in Information Processing Speed in
Children with Multiple Sclerosis
Bigi S.1, Marrie R.2, Till C.3, Akbar N.4, Yeh E.1, Feinstein A.5,
Banwell B.6
1
Division of Neurology, The Hospital for Sick Children,
Toronto, Canada, 2Departments of Internal Medicine and
Community Health Sciences, University of Manitoba,
Winnipeg, Canada, 3Department of Psychology, York
University, Toronto, Canada, 4Division of Neurology, The
Hospital for Sick Children, Toronto, Canada, 5Department of
Psychiatry, Sunnybrook Health Sciences Centre, Toronto,
Canada, 6Division of Neurology, The Children’s Hospital of
Philadelphia, Philadelphia, United States
Background: Information processing speed (IPS) increases with myelination. Decreased IPS is often the first sign of neurocognitive impairment in children and teens with multiple sclerosis (MS). Prompt
identification of pediatric MS patients with IPS impairment requires a
sensitive testing metric that can be administered in a clinical setting. The
computerized version of the Symbol Digit Modalities Test (c-SDMT)
measures IPS over eight consecutive trials/session as well as expected
faster performance over each of the eight trials. The c-SDMT has never
been evaluated in a pediatric MS cohort and normative data in healthy
children and teens is lacking. Objectives: This article aims (1) to
establish normative c-SDMT performance and test-retest reliability in
Epilepsy
Intrauterine Epileptic Seizures: Possible?
FP057
Kurlemann G.1, Althaus J.2, Schwartz O.3, Rödiger M.4,
Fiedler B.2
1
Klinik für Kinder und Jugendmedizin, Allgemeine
Pädiatrie, UKM, Neuropädiatrie, Münster, Germany, 2Klinik
für Kinder- und Jugendmedizin, Universitätsklinikum
Münster, Allgemeine Pädiatrie, Bereich Neuropädiatrie,
Münster, Germany, 3Klinik für Kinder und Jugendmedizin,
Allgemeine Pädiatrie, Neuropädiatrie, Münster, Germany,
4
Klinik für Kinder und Jugendmedizin, Allgemeine
Pädiatrie, UKM, Neuropädiatrie, Münster, Germany
Intrauterine epileptic seizures have rarely been reported to date and are
surely underdiagnosed, as the possibility is not taken into consideration.
We report on three of our cases and two successfully treated intrauterine cases. In all the three cases, the mothers experienced two different
qualities of child movement beginning roughly in the 24th week of
pregnancy. Fetus movement they felt to be normal and prolonged “hard”
stereotype movements of a rhythmic character, which they had not
discussed with their gynecologists. The following postpartum diagnoses
were made: (1) catastrophic infantile epilepsy in tuberous sclerosis, (2)
epileptic encephalopathy of the neonate with evidence of SCN2A
mutation, and (3) pyridoxine-dependent epilepsy. In subsequent pregnancies of (1) the child’s movements were always normal and not
comparable with the child’s movements during the first pregnancy. In
the family with the index child with pyridoxine-dependent epilepsy,
there were four subsequent pregnancies with normal child’s movements, which the mother treated on her own initiative taking 100 mg of
pyridoxine beginning in the 14th week of pregnancy; two further
children in this family have a pyridoxine-dependent epilepsy. In the
literature to date, 14 pregnancies with intrauterine epileptic seizures of
the fetus with findings similar to our pregnancy studies have been
reported. Rhythmic stereotype child movements are indicative of
intrauterine epileptic seizures. In the epileptologic anamnesis of early
childhood encephalopathies, they should be recorded in the anamnesis
as early onset of encephalopathy with unfavorable prognosis. In pyridoxine-dependent epilepsy, intrauterine epileptic seizures can be successfully treated with pyridoxine.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Storm van's Gravesande K.1, Calabrese P.2, Fulda U.3, Kessler
J.4, Kalbe E.5, Mall V.6
1
Lehrstuhl Sozialpädiatrie, TU München, KbO
Kinderzentrum, München, Germany, 2Department of
Psychology and Interdisciplinary Platform Psychiatry and
Psychology Division, Basel, Switzerland, 3Merck Serono,
Darmstadt, Germany, 4Uniklinik Köln, Köln, Germany,
5
Universität Vechta, Vechta, Germany, 6kbo Kinderzentrum,
München, Germany
healthy children (HC); (2) to measure increase in IPS over eight
consecutive trials (¼ one c-SDMT session) in HC and MS patients; and
(3) to compare the overall c-SDMT performance as well as increase in IPS
over eight consecutive trials between HC and MS patients. Methods:
Cross-sectional study including HC and MS patients aged 8 to 18 years,
divided into five age epochs (of 2 years each). IPS was assessed using the
mean time per trial on eight consecutive trials on the c-SDMT. Testretest reliability was evaluated using intraclass correlation coefficient
(ICC). Multiple linear regression models on rank transformed data were
used for predictive analyses in HC. Results: A total of 478 HC (237
females, 49.5%) and 26 MS patients (22 females, 84.6%) participated in
the study. ICC was 0.91 in HC across all age groups. Overall, HC showed a
significant increase in IPS per age epoch (p < 0.0001). Academically
gifted children were faster compared with non gifted children (p ¼
0.0006). Overall, c-SDMT performance did not differ between children
with MS and HC (p ¼ 0.078). HC between 12 to 18 years showed a
significant increase in IPS over eight consecutive trials compared with
younger children, however, patients with MS failed to show this increase
in IPS over trials (p ¼ 0.22). Significance and Conclusions: The c-SDMT
reliably measures IPS in healthy children and adolescents. Although
overall performance of the c-SDMT did not identify MS patients as
impaired, the failure to perform the test more quickly over the trials
suggests that MS patients may be less able to access neural networks
subserving practice efficiency.
S20
Abstracts
Munich, 17th to 19th September 2014
FP058
Long-Term Follow-Up of Patients with BNS
Epilepsy for More Than 30 to 40 Years: First
Results
Munich, 17th to 19th September 2014
Fiedler B.1, Krois-Neudenberger J.1, Althaus J.1, Weber Y.2,
Kurlemann G.1
1
Klinik für Kinder- und Jugendmedizin,
Universitätsklinikum Münster, Allgemeine Pädiatrie,
Bereich Neuropädiatrie, Münster, Germany, 2Hertie Institut
für Klinische Hirnforschung, Universität Tübingen,
Neurologie mit Schwerpunkt Epileptologie, Tübingen,
Germany
Blitz-Nick-Salaam (BNS) epilepsy (syn. West syndrome) is one of the
severest forms of epilepsy generally involving impairments in child
development which lead to permanent disability. In the literature, there
are only a few studies of the long-term progression of the West
syndrome and the development of affected children. Most follow-up
periods described in these studies end before the affected children are
10 years old, and the majority of follow-ups do not exceed 60 months.
We examined a total of 447 (187 females and 260 male) former patients
with West syndrome who were diagnosed between 1970 and 2010.
Patients were assessed regarding the following: progression of epilepsy,
therapy regimen, comorbidity, life quality, restrictions in daily life,
depression scale, quality of sleep, socioeconomic status, school education, housing situation, driving license, severe disabilities, achieved
motoric, and mental development levels. We report on the first group
in the period between 1970 and 1980. The group contains 51 patients,
34 with symptomatic and 17 with idiopathic West syndrome. Overall, 18
patients (35%) are deceased. In 10 cases, the cause of death is unclear, a
direct connection to epilepsy existed in 2 cases (status epilepticus, death
under adrenocorticotropic hormone therapy). Of the 33 surviving
patients, 18 have consented to a clinical follow-up examination. Of
these patients, three have a secondary school-leaving certificate and
lead an independent life. One of the patients is now a practicing doctor.
The remaining 15 patients were living in homes for handicapped or at
home with their parents. They have either graduated from a specialneeds school or have no school-leaving certificate at all. Of 18 patients, 9
still have persisting epileptic seizures. In the group with idiopathic West
syndrome patients, their legal guardian agreed to a genetic follow-up
examination in seven cases. The long-term course of former West
syndrome patients confirms the known poor prognosis for the further
neurological development of the patients. In our small follow-up group,
15 of 18 patients do not lead independent lives. The high death rate of
35% during the observation study over 30 to 40 years is striking.
FP059
lesion (¼ FCD type III according to the new ILAE classification) were
excluded. Results: The overall number of patients with FCD types II and I
operated during the period from January 2002 to December 2013 were
154; only 28 of 154 (12% of the FCDs) were FCD type Ia (14 girls). Age at
onset of epilepsy were as follows: within the 1st year n ¼ 16, within the
2nd year n ¼ 5, 3rd to 6th year n ¼ 5; > 6th year n ¼ 2. Characteristic
magnetic resonance imaging (MRI) findings ranged from volume reduction of the temporal white matter (minimum) to hypoplasia of one
entire hemisphere (maximum), with subtle increased signals in T2 and
fluid attenuated inversion recovery (FLAIR) sequences. Epileptogenic
areas were at minimum restricted to the temporo-occipital region, at
maximum hemispheric, but never restricted to just one lobe. No FCD
type Ia was seen in frontal, parietal, or anterior temporal areas without
involvement alos of posterior-temporo-parietal/occipital regions. A
blurred of the gray-white matter junction was confirmed in all the
cases by pathology, but observed by MRI in only 20%. Electroencephalography (EEG) never showed the typical “ictal-like-pattern/continuous
epileptiform discharges” of FCD type II. More than half of the patients
suffered from severe mental retardation. Types of resections were as
follows: temporo-parieto-occipital n ¼ 9, temporo-occipital n ¼ 8,
subtotal hemispheric (everything but motor) n ¼ 6, parieto-occipital
n ¼ 3, frontotemporal n ¼ 1; and fronto-temporo-parietal n ¼ 1. A
second operation was performed in 10 patients (two hemispherotomies). Seizure outcome after the last operation (Engel class) I: n ¼ 14; II:
n ¼ 5; III: n ¼ 5; and IV: n ¼ 4. Conclusion: Patients with FCD type Ia
show only nonspecific characteristics in the EEG and in the MRI (volume
reduction of the white matter, subtle increased signals on T2, and FLAIR
when myelination is advanced)—in contrast to, for example , FCD type
IIb. FCD type Ia seems to be a pathology of the posterior temporoparietal/ occipital brain regions, with variable interindividual extension
to more central and frontal areas. Whenever the suspicion of the
presence of an FCD type Ia is raised in a young child with a severe
epilepsy, early referral to an experienced pediatric epilepsy surgery
center is recommended.
Reference
1 Blümcke I, Thom M, Aronica E, et al. The clinicopathologic spectrum
of focal cortical dysplasias: A consensus classification proposed by an
ad hoc Task Force of the ILAE Diagnostic Methods Commission.
Epilepsia 2011;52(1):158–174
Isolated Focal Cortical Dysplasias Type Ia As a
Cause of Severe Focal Epilepsies in Children
Holthausen H.1, Pieper T.1, Coras R.2, Hartlieb T.1, Pascher
B.1, Weber K.1, M. Herberhold T.1, Kudernatsch M.3, Winkler
P.1, Staudt M.1, Blümcke I.2
1
Neuropediatric Clinic and Clinic for Neurorehabilitation,
Epilepsy-Center for Children and Adolescents, Schön Klinik
Vogtareuth, Vogtareuth, Germany, 2Neuropathological
Institute, University Clinic, Erlangen, Germany, 3Clinic for
Neurosurgery and Epilepsy Surgery, Schön Klinik
Vogtareuth, Vogtareuth, Germany
Background: According to the new International League Against Epilepsy Classification of focal cortical dysplasias (FCDs),1 isolated type I
FCDs are subdivided in FCD type 1a ¼ vertical dyslamination, FCD type Ib
¼ horizontal dyslamination, type Ic ¼ combination of both dyslaminations. The characteristics of the epilepsies caused by these pathologies
are not well known, which leads often to delays for presurgical evaluations. Objective: This article aims to investigate if there are peculiar
constellations by which one would be alerted to think early during the
diagnostic process that FCD type Ia could be cause of an epilepsy.
Methods: Retrospective analysis of the data of the epilepsy surgery
database of our center of operated patients with histologically confirmed FCD type Ia. Patients with “FCD type I” operated before 2002
(before neuropathological judgments by I. Blümcke/R. Coras) and patients with FCD type Ia-like changes in association with a principle
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
FP060
Combination of Subdural Electrodes with
Intracerebral Electrodes—Using the Advantages
of Both Electrode Types for Invasive Presurgical
Evaluation in Children
Herberhold T.1, Pieper T.1, Kudernatsch M.2, Holthausen H.3,
Winkler P.1, Blümcke I.4, Coras R.4, Staudt M.1
1
Schön Klinik, Klinik für Neuropädiatrie und Neurologische
Rehabilitation, Epilepsiezentrum für Kinder und
Jugendliche Vogtareuth, Germany, 2Schön Klinik, Klinik für
Neurochirurgie, Vogtareuth, Germany, 3Schön Klinik, Klinik
für Neuropädiatrie und Neurologische Rehabilitation,
Epilepsiezentrum für Kinder, Vogtareuth, Germany,
4
Friedrich-Alexander-Universität Erlangen-Nürnberg,
Neuropathologisches Institut, Erlangen, Germany
Introduction: The use of subdural electrodes for invasive electroencephalography (EEG) allows to evaluate large brain areas and to perform
functional topographical mapping, whereas data from deep or subcortical structures are recorded insufficiently. Intracerebral electrodes, in
contrast, allow the registration of electrical activity especially of deeper
structures (like sulci or mesial cortical areas), but registration is
restricted to the tissue around the electrode. The combination of both
electrode types overcomes these limitations. Patients and Methods:
Retrospective analysis of 35 patients (since September 2009) who
underwent invasive presurgical evaluation using the combination of
Abstracts
S21
Munich, 17th to 19th September 2014
FP061
Visual fMRI under General Anaesthesia in
Children with Therapy Refractory Epilepsies
Selch C.1, Pieper T.1, Sarmiento C.2, Staudt M.1
1
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurologische Rehabilitation, Epilepsiezentrum für Kinder
und Jugendliche Vogtareuth, Germany, 2Schön Klinik
Vogtareuth, Klinik für Anästhesiologie, Intensivmedizin und
Schmerztherapie, Vogtareuth, Germany
bilateral occipital activation including the visual cortex was detected. Of
the six cases, two showed unilateral occipital activation, representing a
lack of activation of the affected occipital lobe in two patients with
vascular processes. In the patients who had been successfully assessed
by clinical visual field testing the two examination methods showed
congruent results. Discussion: Visual fMRI under general anesthesia is
easy to perform and provides reliable results independent of the
patient’s age, cooperation, or cognitive function. The information about
an existing or missing activation of one occipital lobe is useful for
planning processes in epilepsy surgery.
FP062
Comprehensive NGS-Based Diagnostics in More
Than 1,000 Patients with Epileptic Disorders
Jüngling J.1, Prehl I1, Döcker M.1, Reicherter K.1, Hoffmann
J.1, Grau T.1, Russ A.C.1, Fehr S.1, Singh Y.1, Stöbe P.1, Battke
F.1, Lemke J.1, Lerche H.1, Biskup S.1, Hörtnagel K.1
1
CeGaT GmbH, Tübingen, Germany
Purpose: Epileptic disorders have a very heterogeneous background
and display a major genetic contribution. Identifying the underlying
molecular defect can be very valuable to improve diagnosis, introduce
new treatment options, and to estimate recurrence risks. For this
purpose, we have developed a comprehensive diagnostic panel.
Method: A total of 465 relevant genes were selected from the literature,
and subdivided into subpanels according to their phenotypes. Customized target enrichment and National Geodetic Survey were performed,
followed by bioinformatic analysis. Variants with a global minor allele
frequency < 5% were chosen for evaluation and identified mutations
were validated by Sanger sequencing. Results: In our study, over 1,000
patients with epileptic disorders were analyzed. Overall, 20% of patients
had pathogenic mutation(s) and 29% were inconclusive. Inconclusive
variants included unknown but predicted pathogenic variants, and
nonsegregation of identified variants. About 51% of the cases remained
unsolved. We observed rare variants in 203 different genes. Mutations
within SCN1A, SCN2A, CACNA1A, MECP2, and KCNT1 were identified
most frequently. Across the cohort, 78 genes were identified as causative
only once, emphasizing the advantage of diagnostic panels for rare
conditions. Conclusion: We have developed a highly reliable and costefficient diagnostic NGS panel to analyze the genetic basis of epilepsies.
We detected mutations in patients with clear as well as unspecific
epilepsy phenotypes, and also in patients suffering from very rare
conditions. This enables a better understanding of genotype-phenotype
correlations, and gives new insights into complex modes of inheritance
including the combinatorial effects of variants.
Introduction: Assessment of the visual field is an integral part of the
clinical neurological examination of children with therapy refractory
epilepsies. Especially in the field of epilepsy surgery, the evaluation of
any preoperatively existing visual field defects is important with regards
to surgical planning and the risk estimation of additional postoperative
deficits. However, performing a formal perimetry or a clinical visual field
examination using confrontation techniques is often not possible in
children with therapy refractory epilepsies due to young age of the
patients, cognitive impairment, or lack of cooperation. We report first
experience with visual functional magnetic resonance imaging (fMRI)
examinations under general anesthesia. Patients: We examined six
patients aged 1 to 9 years (mean age, 5.5 years) with focal therapy
refractory epilepsies due to vascular processes (3/6), tumors (1/6) or
cortical dysplasias (2/6). Of the six patients, five had cognitive impairment, one patient had normal cognitive function. Formal perimetry
was not possible in any of the patients, exploratory analysis of the visual
field using confrontation techniques was possible in two of six patients,
showing hemianopia in one patient and was normal in the other patient.
Methods: fMRI (1.5 T, EchoPlanarImaging, Block Design, 30 second
block length, total duration 5:30 minutes) was performed in the context
of a high-resolution structural cranial MRI examination under general
anesthesia (Sevoflurane 0.8-0.9 MAC). Visual stimulation was performed as whole field flickering through closed eyelids using a stroboscope flashlight. Visual stimulation was performed at the end of the MRI
examination to minimize confounding effects of medication used for
anesthetization (e.g., benzodiazepines). Results: The examination
showed plausible results in five of six cases. In three of six cases a
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
subdural and intracerebral electrodes was done. Etiology was focal
cortical dysplasia (FCD) type II (n ¼ 21), tuberous sclerosis (n ¼ 8),
benign brain tumors (n ¼ 5), and not specified (n ¼ 1). Age at onset of
epilepsy was 2.6 years (range, 0.1-11 years), age at epilepsy surgery was
10.2 years (range, 2.3-17 years), average follow-up was 28 months
(range, 9-50 months), localization of epileptogenic lesion was frontal
(n ¼ 17), centroparietal (n ¼ 1), temporal (n ¼ 6), temporo-parietooccipital (n ¼ 5), and others (n ¼ 6). Intracerebral electrodes were
planned and implanted according to data of the noninvasive EEG,
magnetic resonance imaging (MRI) and semiology by using neuronavigation (VarioGuide, Brainlab AG, iPlan Cranial 2.6, Feldkirchen,
Germany). Post-implantational cMRI showed the localization of the
implanted electrodes; only slight deviations from the planned trajectories occurred. Complications were not observed. After the implantation,
video-EEG monitoring was performed for 10 days. Abnormal interictal
activity was recorded only on the intracerebral electrodes in 4 of 35
patients, only on the subdural electrodes in 5 of 35 patients and on both
electrode types in 26 of 35 patients. Seizure onset occurred only on the
intracerebral electrodes in 6 of 35 patients, only on the subdural grids in
5 of 35 patients, and on both types of electrodes in 19 of 35 patients.
Postoperative outcome (Engel classification): class 1: n ¼ 22 (63%), class
2: n ¼ 3 (8%), class 3: n ¼ 8 (23%), and class 4: n ¼ 2 (6%). Discussion: 1.
The combination of subdural electrodes with intracerebral electrodes is
safe. 2. Neuronavigation enables precise implantation of intracerebral
electrodes. 3. Most patients showed abnormal EEG activity on both
electrode types. Surprisingly interictal (ictal) findings were restricted
either to intracerebral electrodes or to subdural electrodes in 9 of 35 (11/
35) patients. 4. The combination of subdural grids with intracerebral
electrodes enhances the diagnostic yield of invasive evaluations. Data
obtained from each type of electrodes may influence the design of the
resection significantly. 5. Moreover, the intracerebral electrodes can be
used as a strategic guiding structure for the resection (small deeply
located epileptogenic lesions, proximity to functional relevant cortex, or
white matter tracts).
S22
Abstracts
Munich, 17th to 19th September 2014
FP063
De Novo SCN2A Mutations Cause Variable
Phenotypes in Children with Epilepsy
Munich, 17th to 19th September 2014
Wolff M.1, Bast T.2, Loddenkemper T.3, Jillella D.3, Döcker
M.4, Wong-Kisiel L.5, Möller R.6, Weckhuysen S.7, Ceulemans
B.8, Klepper J.9, Baumeister F.10, Finetti C.11, Kurlemann G.12,
Muhle H.13, Kluger G.14
1
Universitäts-Klinik für Kinder- und Jugendmedizin,
Neuropädiatrie, Tübingen, Germany, 2Epilepsiezentrum
Kork, Kinderklinik, Kehl-Kork, Germany, 3Division of
Epilepsy and Clinical Neurophysiology, Boston, Boston
Children’s Hospital, Harvard Medical School, United States,
4
CeGaT GmbH, Tübingen, Germany, 5Division of Child and
Adolescent Neurology, Department of Neurology, Mayo
Clinic, Rochester, United States, 6Danish Epilepsy Centre,
Dianalund, Dänemark, 7Department of molecular genetics,
University of Antwerp, Neurogenetics group, Antwerpen,
Belgien, 8Pediatric Neurology, Department of Neurology,
University Hospital of Antwerp, Antwerpen, Belgien,
9
Klinikum Aschaffenburg, Neuropädiatrie, Aschaffenburg,
Germany, 10Children’s Hospital, RoMed Klinikum,
Rosenheim, Germany, 11Klinik für Kinder- und
Jugendmedizin, Elisabeth-Krankenhaus, Essen, Germany,
12
Universitäts-Kinderklinik Münster, Schwerpunkt
Neuropädiatrie, Münster, Germany, 13Klinik für
Neuropädiatrie, Universitätsklinikum Schleswig-Holstein,
Kiel, Germany, 14Epilepsy Center for Children and
Adolescents, Schön Klinik, Vogtareuth, Germany
Purpose: Mutations in the sodium channel gene SCN2A have been
associated with benign epileptic phenotypes such as benign familial
neonatal-infantile seizures. Recently, several de novo SCN2A mutations
have been found in children with more severe forms of epilepsy. Here,
we describe the phenotypic spectrum of a cohort of children with drug
resistant epilepsies due to de novo SCN2A mutations. Patients and
Methods: Children with drug resistant and otherwise unexplained
epilepsies were screened for SCN2A mutations across multiple centers
using next generation sequencing. Clinical, electroencephalography
(EEG) and magnetic resonance imaging (MRI) data were analyzed in
the SCN2A positive cases. Results: A total of 16 children with de novo
SCN2A mutations were identified. The age of seizure onset ranged from 1
day to 3 years. Children with neonatal onset (n ¼ 7) either exhibited
severe epileptic encephalopathy with multifocal seizures (n ¼ 4) and
suppression burst EEG pattern or transitory epilepsy with cessation of
seizures during the first year of life (n ¼ 3). Of interest, sodium channel
blockers reduced seizure frequency in most cases. The other children (n
¼ 9) presented various seizure types including tonic-clonic or hemiclonic, myoclonic, myoclonic-tonic, atonic, and focal seizures as well as
atypical absences or spasms of later onset (mean age, 2 years). Most of
the children showed decreased muscle tone and severe mental disability. Abnormal MRI patterns were found in six cases. Conclusion: De novo
SCN2A mutations seem to cause more severe epilepsies compared with
the inherited SCN2A mutations reported so far. The clinical spectrum
includes various phenotypes possibly due to different properties of the
affected sodium channels. Electrophysiological analyses of the mutated
channels are needed to check this hypothesis.
FP064
SCN2A Mutation Causing Benign Neonatal
Infantile Seizures and Later Episodic Ataxia
Cag C.1, Weber Y.2, Lerche H.2, Bast T.1
1
Epilepsiezentrum Kork, Kinderklinik, Kehl-Kork, Germany,
2
Universitätsklinikum Tübingen, Neurologische Klinik,
Tübingen, Germany
The 2.5 years old boy presented with clusters of tonic and hypomotor
seizures starting at age 7 days. The seizures did not respond to a
treatment with vitamin B6, phenobarbitone, levetiracetam, and topiramate. He became seizure free with 7 months after adding oxcarbazepine. The initial EEGs were normal and bioccipital sharp waves were
seen only once at age 7.5 months. After several normal controls, right
central benign sharp waves were observed from 17 months of age. The
patient initially presented with a marked muscular hypotonia with only
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
slow improvement. The development was slightly retarded. MRIs at age
3 weeks and 6 months were normal, as was the brought neurometabolic
work-up. The parents reported an inability to move in the context of a
febrile infection at 15 months of age. Attacks of an episodic ataxia started
at 22 months of age and occurred once or twice a month since then. In
the morning, the gait of the complete responsive child is unsteady. The
severity of symptoms increases during the day until the boy is unable to
stand or walk. The attacks last at least for hours and usually the whole
day. Genetic testing revealed an SCN2A mutation c.788 C >T; p.A263V
that has previously been described1 in a child with almost identical
symptoms (but in addition attacks with pain). A gain of function was
revealed by physiological analysis. In this described case, trials with
phenytoin, valproate, acetazolamide, oxcarbazepine, carbamazepine,
gabapentin, clobazam, levetiracetam and topiramate failed to control
the attacks. Both the cases demonstrate the variability of phenotypes in
sodium channel mutations and the link of seizures and movement
disorders.
Reference
1 Liao Y, Anttonen AK, Liukkonen E, et al. SCN2A mutation associated
with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and
pain. Neurology 2010;75(16):1454–1458
FP065
Knowledge and Attitudes of Schoolteachers,
Nursery School Teachers and Students in
Teacher Training toward Epilepsy in Children
Bertsche A.1, Dumeier H.2, Neininger M.2, Bernhard M.2,
Syrbe S.2, Merkenschlager A.2, Zabel J.3, Kiess W.2, Bertsche
T.2
1
Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für
Kinder- und Jugendmedizin, Leipzig, Germany, 2Universität
Leipzig, Klinische Pharmazie, Leipzig, Germany,
3
Universität Leipzig, Biologiedidaktik, Leipzig, Germany
Problem: Schools and nursery schools care for most children during
daytime. Thus, schoolteachers and nursery school teachers have an
important role to play in the care of children with epilepsy. Yet, the level
of knowledge about epilepsy among teachers is not known. Aim: This
article aims to assess knowledge and attitudes toward epilepsy in
teachers and students in teacher training by a questionnaire survey.
Results: A total of 1,243 questionnaires were filled by 302 school
teachers, 883 nursing school teachers, 56 students in teacher training,
and 2 others. Of the 1,243, 668 (54%) respondents had prior familiarity
with the topic of epilepsy. Of the 1,243, 140 (11%) respondents stated to
have been actively involved in an emergency dealing with epilepsy, 148
(12%) as observers. Only 214 (17%) of respondents feel well prepared for
an emergency. An emergency medication had already been applied by
79 (6%) respondents, only 186 (15%) stated they would be willing to
administer an available emergency medication without any precondition. Only 75 (6%) respondents were able to correctly relate all symptoms mentioned in the questionnaire, including a description of an
absence, to a possible epileptic seizure. In an open-ended question about
possible causes for death in a seizure, status epilepticus and drowning
were rarely mentioned. Of the 1,243 questionnaires, 233 (19%) respondents even believe that epileptic seizures cannot result in death. Overall,
56 (5%) respondents would not take a child suffering from epilepsy on an
excursion, 760 (61%) only under partially unrealistic circumstances.
Also, 606 (49%) respondents are afraid of legal consequences to an
incorrect response to a seizure. Special examination regulations for
students with epilepsy were only familiar to 39 of 302 (13%) school
teachers and 7 of 56 (12%) students in teacher training. Of the 403
teachers, 129 (32%) teachers with more than 20 years of professional
experience claimed never to have had a child suffering from epilepsy in
their care. Measure against the prevalence of childhood epilepsy, this
claim seems highly unlikely. In total, 1,066 (86%) respondents expressed
a desire to know more about epilepsy. Teachers expressed a desire for
training sessions and for clear legal protection. Conclusion: Many
respondents have displayed basic knowledge about epilepsy and its
medical treatment. Yet, the symptoms of the disease and its medical
Abstracts
S23
Munich, 17th to 19th September 2014
treatment in complexity are known sufficiently to a minority of teachers
and students in teacher training. Further action is necessary to address
this problem.
Traumatic Brain Injury in Children and Adolescents
FP066
Remission from Unresponsive Wakefulness in
Children and Adolescents: Differences between
Traumatic versus Hypoxic Origin
Introduction: Children and adolescents with severe traumatic (traumatic brain injury [TBI]) or hypoxic (hypoxia) events are often transferred for neurorehabilitation in a state of unresponsive wakefulness.
We searched for potential differences between these two subgroups in
the time elapsing before the first reproducible reactions occur. Patients
and Methods: A total of 16 patients (seven girls) who had been admitted
in unresponsive wakefulness after TBI (n ¼ 9) or hypoxia (n ¼ 7) were
included. Remission was monitored during a period of 24 weeks using
our own activity-based instrument (RemiPro1). This included a documentation when first reproducible reactions (e.g., smiling, or head
version toward a stimulus) are observed while activities of daily living
are performed with the child. Results: Of the nine children, eight after
TBI and five of seven children after hypoxia showed such reproducible
reactions during the observation period of 24 weeks. Of these, the
children with TBI showed such reactions earlier (median 6 weeks) than
the children after hypoxia (median 13 weeks; p < 0.05; Mann-Whitney
U, one-tailed test). Discussion: Our analysis confirms previous reports of
a faster remission in children with TBI as compared with children after
acute hypoxic events.
P001
1 Romein E. The Remission Profile for Children and Adolescents after
Severe Acquired Brain Injury: Establishing Validity Evidence. Unpublished Masterthesis. Karolinska Institutet, Stockholm; 2003
Reintegration to School after Craniocerebral
Injury
Reutlinger C.1
1
HELIOS Klinik Geesthacht, Neuropädiatrie, Geesthacht,
Germany
Introduction: After craniocerebral injury during childhood and adolescence, often cognitive limitations remain for a long time. This can make
reintegration to school difficult and leads to negative emotions toward
school and therefore to reduction of quality of life and participation.
Benz und Ritz 2003 demand an early beginning and extensive rehabilitation which especially regards school. As this time inclusion in school
has become more and more important. The aim of the following
investigation was to evaluate reintegration to school according to
current data of the HELIOS Klinik Geesthacht. Methods: The epicrisis
of all patients between 6 and 18 years, which were inpatients of the
HELIOS Klinik Geesthacht between 2008 and 2013 were considered. We
investigated which motorical and cognitive impairments remained at
the date of discharge and which school we recommended. Results:
Almost all patients had impairments of attention partly also of memory
and speed of operation. Nevertheless, we recommended reintegration in
the old class by 50% of the children and adolescents. By around 30%, we
recommended recapitulation of the old class, change to another regular
school, a regular school with a personal assistant, or a class specialized in
inclusion. Only 20% changed to a special school or a special institution or
were so severely handicapped that they changed to an institution
specialized for Phase F with a special school. The patients who moved
Porencephaly in the Child, Multifocal
Intracerebral Hemorrhages in the Mother: A
New Mutation in the COL4 A1 Gene (c.2662G>A)
Abredat K.1, Abicht A.2, Fiedler A.1
1
Klinikum St. Marien, Klinik für Kinder und Jugendliche,
Amberg, Germany, 2Medizinisch Genetisches Zentrum,
München, Germany
Porencephalies in newborns can have many causes. We report the case
of a premature infant of 37th week of gestation with the incidental
findings of porencephaly and cerebellar atrophy in the ultrasound of the
brain. In the the 24-year-old mother, multifocal intracerebral hemorrhages occurred post partum; in addition, she had congenital cataracts
and had suffered ischemia of the basal ganglia with transient paresis of
the right hand during pregnancy. The synopsis of all these symptoms in
mother and daughter suit the idea of a mutation of the collagen-IVgenes COL4A1 and COL4A2 with small vessel disease. We found a new
mutation with sequence modulation on COL4A1 gene (c.2662G>A),
which was unknown until now. The genes COL4A1 and COL4A2 (both on
chromosome 13q34) are coding for elements of collagen IV, which is
forming an essential part of the basal membranes. Inheritance is
autosomal dominant.
Floating-Harbor Syndrome: A Case Report
P002
Reference
FP067
Poster Presentations
Albers K.1, Prietsch V.1, Jung C.2
1
Städtisches Klinikum, Klinik für Kinder- und
Jugendmedizin, Karlsruhe, Germany, 2Praxis für
Humangenetik, Karlsruhe, Germany
Introduction: The Floating-Harbor syndrome (FHS) is a rare short
stature syndrome, which is caused by a SRCAP gene mutation and leads
to characteristic facial appearance, a developmental disorder of variant
extent, and a distinct short stature. Case Report: We saw a 1.6 years old
boy with delayed development of motor skills since birth, poor feeding,
nail dysplasia, and facial abnormalities with high forehead, deep-set
wide-eyed, broad nasal bridge, short philtrum, wide mouth and narrow
upper lip, wide fingertips, and severe language delay. Suspecting a
genetic disease, a CGH (comparative genomic hybridization) array
analysis was done, which resulted in no pathological findings. Because
of the characteristic facial dysmorphisms, we suspected an FHS and
performed a molecular genetic analysis of the SRCAP gene. Molecular
analysis identified a typical mutation in exon 34, c.7330C > T (p.R2444X)
in a simple, heterozygous dose. The mutation was not detected in the
parents so that it is a de novo mutation in the patient. Because of the
autosomal dominant mode of inheritance, the recurrence risk is 50% for
offspring of the patient. Discussion: The FHS is a rare but very characteristic, genetic short stature syndrome. If the individual shows typical
facial appearance, the FHS can be detected by a targeted molecular
genetic investigation. The facial dysmorphic features are particularly
distinct in midchildhood. The expressive language delay is a cardinal
feature of the syndrome and a high-pitched voice or a nasal quality to
the voice is often reported. Other symptoms are learning or mild
intellectual disability, behavioral problems such as attention deficit
disorder, anxiety, and mannerisms, as well as rare urogenital and
cardiac malformations. Differential diagnoses include other dysmorphic
syndromes such as the Rubinstein-Taybi syndrome and microdeletion
22q11.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Hessenauer M.1, Romein E.2, Kluger G.1, Berweck S.1,
Staudt M.1
1
Schön Klinik, Klinik für Neuropädiatrie und Neurologische
Rehabilitation, Epilepsiezentrum für Kinder und
Jugendliche Vogtareuth, Germany, 2Gilhoc sur Ormeze,
France
into a special pedagogical institution often had psychiatric problems
before the injury which were often stressed due of the injury.
Conclusion: With an extensive and early beginning, neurologic rehabilitation most of the children and adolescents can be reintegrated into a
regular school. Therefore, a close contact between rehabilitation clinic
and the school at home is necessary. During the further process, it
should be investigated if a multimodal reintegration can avoid the
problems described in the literature.
S24
Abstracts
Munich, 17th to 19th September 2014
P003
Undine-Syndrome: Really Only a Disease of
Infants?
Munich, 17th to 19th September 2014
Althaus J.1, Fiedler B.1, Rödiger M.1, Große-Onnebrink J.2,
Werner C.2, Linden T.1, Kurlemann G.3
1
Klinik für Kinder- und Jugendmedizin,
Universitätsklinikum Münster, Allgemeine Pädiatrie,
Bereich: Neuropädiatrie, Münster, Germany, 2Klinik für
Kinder- und Jugendmedizin, Universitätsklinikum Münster,
Allgemeine Pädiatrie, Bereich: Pädiatrische Pneumologie,
Münster, Germany, 3Klinik für Kinder- und Jugendmedizin,
Universitätsklinikum Münster, Allgemeine Pädiatrie,
Neuropädiatrie, Münster, Germany
Introduction: The congenital central hypoventilation syndrome (CCHS)
is a rare, hereditary disorder involving dysfunction of autonomous
respiratory control. One of the causes of CCHS that has been described
is a mutation of the PHOX2b gene. We report the case of a female patient
first diagnosed as having a PHOX2b mutation at the age of 17 years.
Results/Case Description: Episode I: Several external presentations of a
17-year-old girl, who had been healthy up until then, with persistent
headaches, paresthesia in the face, slurred speech and unsteady gait.
Initial diagnosis: Ophthalmologist findings, electroencephalography
(EEG), laboratory and cranial magnetic resonance imaging (c-MRT)
were all normal. Slight improvement under intravenous analgesia was
observed. Episode II: Persisting condition, admittance to a psychiatric
clinic, and start of therapy with olanzapine and tavor were observed.
During medication, hypoventilation with Pco2 80 mm Hg. Transfer to
external pediatric intensive care unit, intubation, and start of antibiotic
therapy for suspected pneumonia. CSF was normal, EEG with slow
activity. Aciclovir therapy for suspected herpes infection was started.
In the process, additional renal failure and transfer to our pediatric
intensive care unit were observed. Initial examination: Paralysis of all
the four extremities, maintained reflexes, and absence of spontaneous
respiration were seen. Further diagnostic evaluation: The further diagnostic evaluation included MRT, electromyography, auditory-evoked
potential, nerve conduction velocity, laboratory diagnostics, and LP.
Oligoclonal bands were present in liquor. Administration of immunoglobulin and cortisone was observed. Improvement of condition with
increasing spontaneous motor functions and spontaneous respiration
was seen. Secondary findings of arterial hypertonia and corresponding
therapy were seen. In the course, development of a psychotic disorder
was also observed. Antibodies for autoimmune encephalitis were
negative. End of antihypertensive therapy as suspected cause of psychosis. Subsequent clinical improvement was seen and the patient was
discharged. Episode III: Readmission with further deterioration and CO2
retention values up to 75 mm Hg. Noninvasive artificial respiration for
suspected central hypoventilation syndrome was started, thereafter,
leading to good CO2 retention values and lasting clinical improvement.
Verification of a PHOX2b mutation was done. Conclusion: The PHOX2b
mutation is one of the causes of the rare CCHS disorder. Although the
disorder manifests itself shortly after birth in most cases, it should be
borne in mind given elevated CO2 retention values and conspicuous
neurological symptoms irrespective of the patient age.
P004
Efficacy of ToeOFF Orthoses on Functional Gait
Parameters in Children with Unilateral Cerebral
Palsy
Altschuck N.1, Bauer C.2, Nehring I.1, Mall V.1, Jakobeit M.2,
Jung N.1
1
kbo Kinderzentrum, Lehrstuhl Sozialpädiatrie der
technischen Universität München, München, Germany,
2
kbo Kinderzentrum, Sensomotorik, München, Germany
Introduction: Gait deviations limiting the activity and participation are
frequently present in ambulatory children with cerebral palsy (CP).
Children with unilateral CP (UCP) often show a “drop foot pattern”
during the swing phase of gait, which may result in secondary functional limitations such as forefoot contact or diminished knee extension
during early stance. The aim of this prospective, controlled study was to
evaluate the effect of the ToeOFF Orthosis (Basko Orthopädie Handelsgesellschaft mbH, Hamburg, Germany) on functional gait parameters,
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
which can be affected due to a drop foot pattern. Methods: The ToeOFF
Orthosis is prefabricated with minimal needs for individual tuning. The
immediate outcome effects of the orthosis were evaluated under three
randomly assigned conditions (walking barefoot, in shoes, and in shoes
with orthosis). A total of 13 children with UCP were assessed (median
age, 9 years [range, 4-14 years]; 7 females, 6 males; Gross Motor
Function Classification System: level I n ¼ 12, level II n ¼ 1). The children
walked at a self-selected speed on an 8 m walkway in a three-dimensional gait laboratory (6 MX VICON cameras; Vicon Motion Systems Ltd.,
Oxford, United Kingdom, 2 AMTI force plates; Advanced Mechanical
Technology, Inc., Watertown, United States and Plug in Gait marker set).
The tested outcomes were the kinematics of the ankle and knee in the
sagittal plane at defined gait events, the ankle power generation at pushoff, and time-distance parameters. One-way analysis of variance was
used for statistical analysis. Results: Significant differences were found
for the ankle kinematics and kinetics. Post hoc analysis revealed a
normalization by wearing the orthosis compared with wearing shoes
only for dorsiflexion at initial contact (orthosis, 5.84 degrees [standard
deviation, SD: 5.97]; shoe, #3.13 degrees [SD, 6]; p < 0.001), foot
progression at initial contact (orthosis, #104.27 degrees [SD, 5.16];
shoe, #94.71 degrees [SD, 3.53]; p < 0.001), and plantarflexion during
loading response phase (orthosis, #3.02 degrees [SD, 2.44]; shoe, •0.96
degrees [SD, 1.26]; p ¼ 0.007) Knee kinematics and time-distance
parameters did not change significantly. Conclusion: Our preliminary
results demonstrate improved dorsiflexion and foot progression angle
at initial contact and the loading response phase during early stance in
children wearing the ToeOFF Orthoses. This suggests a normalization of
functional gait kinematics by ToeOFF Orthoses. The orthoses may
prevent secondary musculoskeletal problems caused by the drop foot
in children with UCP.
P005
Abnormal T2-Hyperintensities in the Dorsal
Brain Stem: Visualization by High-Resolution
Magnetic Resonance Imaging in Children with
Refractory Epilepsies
Anderl J.1, Winkler P.1, Staudt M.1
1
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurologische Rehabilitation, Epilepsiezentrum für Kinder
und Jugendliche, Vogtareuth, Germany
Introduction: Circumscribed T2 signal-hyperintensities with unclear
significance in the dorsal brain stem (cT2si) are occasionally seen on
magnetic resonance images (MRI) scans of infants and children. An
association with vigabatrin therapy has been discussed. Patients and
Methods: High-resolution T2-weighted magnetic resonance images (0.6
mm axial) of 216 patients (age, 5 months-25 years; median, 7.3 years)
were analyzed with respect to the presence of cT2si in the tegmentum
pontis. Results: We detected cT2si in 17 of 223 scans (15/216 patients;
6.9%), ranging in age from 7 months to 6 years (median, 2.1 years). A
detailed anatomical analysis of the high-resolution magnetic resonance
images located the cT2si to the central tegmental tract. Vigabatrin
therapy (> 1 month in the 6 months before magnetic resonance images)
was found in 8 of 15 patients with cT2si (53.3%) and in 15 of 201 patients
without cT2si (7.5%), or 15 of 67 patients (22.3%) looking at the same age
range (range, 0-6 years). Discussion: cT2si is not a rare phenomenon in
children with refractory epilepsies. The central tegmental tract, which is
often affected from the mesencephalon to the inferior olivary nucleus,
could be identified as anatomic correlate. We found cT2si up to the age of
6 years, almost half of the affected patients were not treated with
vigabatrin—in these patients, however, the cT2si appeared less
pronounced. This confirms similar results in literature.1 The pathogenesis of cT2si in the central tegmental tract and the role of vigabatrin
remain unclear.
Reference
1 Aguilera-Albesa S, Poretti A, Honnef D, et al. T2 hyperintense signal of
the central tegmental tracts in children: disease or normal maturational process? Neuroradiology 2012;54(8):863–871
Abstracts
S25
Munich, 17th to 19th September 2014
P006
Usefulness of FACS Analysis of Liquor to Detect
Rare Manifestations of Malignancies in
Childhood: A Case Report
Bachmann M.1, Kropshofer G.1, Klein-Franke A.1, Brunner
J.1, Meraner D.1, Haberlandt E.1, Rostasy K.1
1
Pädiatrie I, Universitätsklinik für Kinder und
Jugendheilkunde Innsbruck, Innsbruck, Austria
P007
Aspiration in Children and Adolescents with
Neurogenic Dysphagia: A Comparison of Clinical
Assessment with Fiberoptic Evaluation of
Swallowing
Beer S.12, Hartlieb T.1, Müller A.1, Granel M.1, Staudt M.1
1
Neuropädiatrie, Schön Klinik Vogtareuth, Germany,
2
Logopädische Praxis LogBUK, Rosenheim, Germany
Introduction: For the therapy of dysphagia, it is of utmost importance to
determine swallowing quality so that one may plan therapy and
recommend adequate foods. Circumstances in a hospital do not always
allow for early on swallowing endoscopy because of lacking resources
(staff and material) or compliance. Then, therapy will have to be based
on hypotheses. In this study, we asked whether clinical assessment
regarding the quality of swallowing is confirmed by fiberoptic evaluation of swallowing (FEES). Patients and Methods: A total of 30 children
and adolescents (age range, 10 months-17.8 years) with neurogenic
dysphagia were assessed for their risk of aspiration. The clinical assessment included the parameters BODS-1, BODS-2, and BODS total score,
and a judgment whether aspiration events occurred (yes/no) for saliva
and for the food consistencies thin liquid/puree/solid. FEES included the
PAS (Penetrations-Aspirations Sore). Results: FEES detected penetrations or aspirations for saliva in 15 of 30 patients (50%), for puree in 13 of
22 patients (59%) and for thin liquids in 13 of 21 patients (62%). The
clinical rating for the risk of aspiration was not confirmed in FEES for
many cases. A false clinical assessment occurred for saliva in 30%, for
P008
Sotos Syndrome 2: A Rare Clinical Presentation
of Sotos-Like Features in Combination with
Epileptic Seizures
Blank A.1, Schmitz N.1, Holinski-Feder E.2, König R.3,
Kieslich M.1
1
Johann Wolfgang Goethe-Universität, Zentrum für Kinderund Jugendmedizin, Neuropädiatrie, Frankfurt/Main,
Germany, 2Medizinisch Genetisches Zentrum, München,
Germany, 3Institut für Humangenetik, Johann Wolfgang
Goethe-Universität, Frankfurt/Main, Germany
Introduction: Characteristic symptoms of children with Sotos syndrome
(OMIM 117550) are an excessive physical growth, macrocephaly, long
narrow face with a slightly protrusive forehead, and an advanced bone
age. In addition, a mental retardation varies among individuals. More
than 60% of patients with Sotos syndrome are caused by mutations in
the NSD1 gene on chromosome 5 (5p35). Clinical Case Here, we report
the case of a male, 13-year-old patient with Sotos-like symptoms.
Because of the strong suspicion of Sotos syndrome, we did molecular
diagnostics (DHPLC analysis) and a subtelomeric analysis (fluorescence
in situ hybridization) to detect mutations and microdeletions in the
NSD1 gene. A conventional chromosome analysis remains without any
result. Cliniconeurological examination shows a boy with a weight
between the 50to 75 percentile (P 50-75), a somatomegaly with a
body height of P 90-97 and a macrocephaly with a head girth P > 97
and large hands and feet. Furthermore, there was a distinct psychomotor retardation and intermittent strabismus diverges left and nystagmus
latens. An outstanding feature was epilepsy with complex partial
nodding seizures with a loss of muscle tonus of the neck muscles (daily
10-20 atonic seizures up to 1.5 minutes). The sister, 2 years older, shows
a similar phenotype consisting of postnatal overgrowth (P > 97) and
macrocephaly (P > 97). Diagnostics: Blood samples from our patient
and his family were investigated by using an oligo-array-comparative
genomic hybridization-test (Cytochip v1.0, BlueGnome, Cambridge,
United Kingdom). Genetic diagnostics reveals a heterozygous deletion
19p13.2, which leads to a Sotos-like syndrome (genomic position:
19:13,161,385-13,270,577; size 110 kb). Diagnostic tests including
electroencephalography, blood sampling with metabolic screening
parameters, skeletal bone age assessment, ECG, and further exploration
of organ functions offer no significant pathological result. The current
cMRT study shows a megalencephaly accompanied by a discrete ventriculomegaly with a prominence of the occipital horns, but shows no
significant pathology or an abnormal brain structure. Conclusion:
Because of our findings, we could present a rare case of a patient
with Sotos syndrome 2 (SOTOS2, OMIM 614753) in combination with a
complex partial epilepsy with atonic nodding seizures of the head.
SOTOS2 is caused by a heterozygous mutation in NFIX gene on chromosome 19p13.3. This heterozygous mutation affects the functionality of
the transcription factor Nuclear Factor I-X (NFIX). NFIX is essential for
chondrocyte differentiation and a mutation leads to a dysregulation of
skeletal growth. Furthermore, NFIX is responsible for the embryonic and
fetal brain development and therefore a possible explanation for syndrome-associated mental retardation and developmental disorder. In
the case of patients with Sotos-like symptoms and (1) an NSD1 analysis
without any variation or (2) an associated epileptic disorder you should
think of SOTOS2 syndrome.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Lymphoblastic lymphomas are the second most common subgroup of
nonHodgkin lymphoma in childhood. The diagnosis is mostly confirmed
by examination of blood or bone marrow, puncture of effusions or
biopsy of lymphoma. Solitaire manifestation of the central nervous
system () is rare and complicates the diagnosis. Here, we present a case
of B cell-lymphoma diagnosed by FACS (fluorescence-activated cell
sorting) analysis of liquor, without participation of bone marrow. A
12-year-old girl presented with waddling gait, fever episodes, fatigue,
and weight loss over 9 months. Examination revealed a reduced
mobility of lumbar and thoracic spine and cautious movement of the
right leg. Laboratory tests showed no remarkable findings, magnetic
resonance image (MRI) of brain and lumbar spine—done at a peripheral
hospital—showed no abnormalities. An ophthalmological examination
showed a chronic papilledema suitable for pseudotumor cerebri. Therefore, a lumbar puncture was done with a normal opening pressure. But a
disturbance of blood-cerebrospinal fluid barrier with a pleocytosis,
reduced glucose level and massively elevated protein could be seen.
Moreover, the leukocytes mainly consisted of lymphocytes and large
cells with polymorphic nuclei. Isoelectric focusing showed oligoclonal
bands in liquor and intrathecal synthesized immunoglobulins. Unfortunately, not enough liquor for further analysis was left. An electroencephalogram showed bilateral cerebral dysfunction with an increase of
slow frequencies, so the magnetic resonance image was repeated. This
time it demonstrated thickening and enrichment of contrast agent of
cranial nerves and of the cervical spinal cord, matching to meningomyelitis. In addition, an 8 ' 8 mm tumor in the glandula pinealis was
seen. The result was consistent with an inflammatory process as well as
with carcinomatous meningitis. Negative serology results and tuberculin test finally excluded neuroborreliosis or tuberculosis. Further investigations included a suboccipital puncture and fluorescence-activated
cell sorting analysis of liquor showed 40% lymphatic blasts, without
participation of blood or bone marrow. The patient was transferred to
the pediatric oncology and therapy according to the NHL-BFM registry
2012 was started. Hence, she showed rapid clinical improvement. This
case shows the importance of flow cytometry of liquor to detect rare
manifestations of malignancies in childhood.
puree in 45%, and for thin liquid in 33%. Conclusion: A pure clinical rating
of aspiration risk in children with neurogenic dysphagia is clearly
insufficient. Instrumental examination such as FEES is to demand for
verification—ideally early in the process of the treatment.
S26
Abstracts
Munich, 17th to 19th September 2014
P009
Presurgical Evaluation in Magnetic Resonance
Image-Negative Frontal Lobe Epilepsy
Munich, 17th to 19th September 2014
Borggräfe I.1, Vollmar C.2, Lösch A.2, Ertl-Wagner B.3, Gerstl
L.1, Heinen F.4, Kreth F.5, Peraud A.5, Noachtar S.6
1
Klinikum der Universität München, Dr. von Haunersches
Kinderspital, Abteilung für Pädiatrische Neurologie,
Entwicklungsneurologie und Sozialpädiatrie, München,
Germany, 2Klinikum der Universität München,
Neurologische Klinik, Epilepsie-Zentrum, München,
Germany, 3Ludwig-Maximilians-Universität München,
Radiologie, München, Germany, 4Dr. von Haunersches
Kinderspital, Klinikum der Universität München, Campus
Innenstadt, München, Germany, 5Department of
Neurosurgery, Ludwig-Maximilians-University, München,
Germany, 6Klinikum der Universität München ‐
Großhadern, Ludwig-Maximilians-Universität,
Interdisziplinäres Epilepsiezentrum, Neurologische Klinik
und Poliklinik, München, Germany
Background and Aims: Medical refractory epilepsy occurs in up to 30 to
40% of epilepsy patients. In some of these patients, resective epilepsy
surgery is curative. Localization of the epileptogenic zone is crucial in
these patients. The aim of this case report is to illustrate the evaluation
of the seizure onset zone in the absence of a magnetic resonance
imaging (MRI) lesion. Methods: A case report of a 7-year-old righthanded girl with medical refractory epilepsy is presented. Presurgical
evaluation was performed using continuous electroencephalography
(EEG)-videomonitoring, high-resolution magnetic resonance imaging
(MRI), invasive EEG-videomonitoring with bilateral strip electrodes and
depth electrodes, ictal SPECT (ECD tracer) with MRI fusion (SISCOM).
Results: Continuous EEG-videomonitoring recorded bilateral tonic seizures 20 seconds before clinical seizure onset within the right central
region. Subtraction of interictal from ictal SPECT showed right central
hyperperfusion. However, high-resolution 3T MRI revealed no lesion.
Bilateral frontal strip electrodes were placed for further lateralization
and EEG seizure onset zone was recorded within the right frontal region.
For further spatial resolution of the seizure onset zone and delineation
of eloquent cortex, a total of nine depth electrodes were placed within
the right prefrontal cortex. On the basis of the results of seizure
recordings of the depth electrodes and cortex stimulation (intra- and
extraoperative), resection of the right superior frontal gyrus was
performed. The specimen was diagnosed with focal cortical dysplasia
type IIb. The patient is seizure free (Engel class I, 1 year of survey) and is
without functional disturbances. Conclusion: Patients might be candidates for resective epilepsy surgery even if high-resolution MRI does not
reveal any lesion but further modalities of presurgical evaluation are
consistent (seizure semiology, SPECT, and invasive EEG recording).
P010
Clinical Consequences of the Revised Diagnostic
Criteria for the Diagnosis of Idiopathic
Intracranial Hypertension
Bubl B.1, Weber P.1
1
Universitäts-Kinderspital beider Basel, Neuro- und
Entwicklungspädiatrie, Basel, Switzerland
Background: The criteria for the diagnosis of idiopathic intracranial
hypertension (IIH) were revised in recent years.1 Objective: Do the
modified criteria of IIH change the diagnosis in clinical practice?
Methods: In a retrospective cross-sectional study, we found 20 children
with the diagnosis of pseudotumor cerebri in the database of the
department of Pediatric Neurology of the University Children’s Hospital
Basel between January 1, 2006 and December 31, 2013. One case was
excluded because of incomplete documentation. The diagnoses were
reevaluated on the basis of the revised criteria mentioned earlier.
Results: All 19 remaining cases had lumbar puncture opening pressures
above 28 cm H2O. In four cases, the diagnosis was revised because of an
assumed cause of intracranial pressure increase (secondary intracranial
hypertension: Graves disease, venous sinus thrombosis, chronic subdural hematoma, and treatment with tacrolimus). In five children,
neither papilledema nor a sixth nerve palsy was present. None of these
patients satisfied the additional neuroimaging criteria (empty sella,
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
flattening of the posterior aspect of the globe, distension of the perioptic
subarachnoid space with or without a tortuous optic nerve, and
transverse venous sinus stenosis). Therefore, 10 of the 19 originally
classified as pseudotumor cerebri patients met the revised criteria of the
ICH. Conclusion: Because of discontinuation of headache and other
ophthalmologic findings other than papilledema and sixth nerve palsy
(e.g., visual field defects and enlarged blind spot) the diagnostic criteria
are limited by the revised criteria, even if a significantly elevated lumbar
puncture opening pressure is present.
Reference
1 Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the
pseudotumor cerebri syndrome in adults and children. Neurology
2013;81(13):1159–1165
P011
Independent Bilateral Hypothalamic
Hamartomas and Gelastic Seizures: What
Treatment to Offer?
Cag C.1, Strobl K.1, Bast T.1, Wiemer-Kruel A.1, Wiegand G.2
1
Epilepsiezentrum Kork, Kehl-Kork, Germany,
2
Universtitätsklinikum Kiel, Neuropädiatrie, Kiel, Germany
We report a case of a 9-year-old boy with normal cognitive and
neurological status. Pharmacoresistant epilepsy started at 2 years of
age when he woke up from sleep with epigastric painful sensations.
During the course, somatosensory seizures with pain in the legs and,
from 3.2 years on, gelastic seizures and dyscognitive seizures occurred.
High-resolution magnetic resonance image (MRI) of the brain revealed
bilateral independent hypothalamic hamartomas in the supramamillary
region. After presurgical evaluation, a decision for an endoscopic resection of the bigger, right-sided hamartoma was made. Seizures improved
transiently after surgery (Engel 3a). However, no significant improvement was noted 6 months after surgery. As the only negative consequence, a marked weight gain followed surgery. Cognitive functions
remained stable. On the basis of this case, we discuss the therapeutic
options for this rare condition which include resection of the contralateral hamartoma or stereotactic laser ablation.
P012
Acute Encephalopathy with Strongly Increased
Protein Level in the Cerebrospinal Fluid:
Unusual Presentation of a Leptomeningeal
Gliomatosis
Company M.1, Alber M.1, Gallwitz H.2, Bender B.3, Ebinger
M.4, Bornemann A.5, Schuhmann M.6, Krägeloh-Mann I.1
1
Pediatric Neurology, University Children’s Hospital,
Tübingen, Germany, 2Children’s Hospital, Memmingen,
Germany, 3Department of Diagnostic and Interventional
Neuroradiology, University Hospital Tübingen, Germany,
4
Pediatric Hematology and Oncology, University Children’s
Hospital, Tübingen, Germany, 5Department of Pathology
and Neuropathology, University Hospital Tübingen,
Germany, 6Department of Neurosurgery, University
Hospital Tübingen, Germany
Background: Leptomeningeal gliomatosis is a rare disease characterized
by diffuse infiltration of the meninges with glial tumor cells but without
solid tumor localization in the central nervous system (). Patients
usually present with subacute symptoms such as headache, cranial
nerve palsy, vomiting, meningitis, and behavioral changes. Case Report:
This 10-year-old boy presented with acute onset behavioral changes,
somnolence, muscular hypertonus, and generalized tonic-clonic seizures. In the past few months, increasing headache plus occasional
vomiting had occurred. On admission, cranial CT scan showed no
pathological findings. Cerebrospinal fluid (CSF) showed a slight pleocytosis with 17/µL cells, elevated lactate plus massive elevation of
protein (1,133 mg/dL). Antibiotic and antiviral treatment was initiated.
Because of signs of a cerebral edema a single dose of prednisolone was
given and he was transferred to our hospital. Infectiological
Abstracts
S27
Munich, 17th to 19th September 2014
P013
Outcome of Severe Traumatic Brain Injury with
Different Mechanisms of Damage Results of
Early Neurologic Rehabilitation in the
Framework of the TBI-Register-Project in North
Rhine-Westphalia
Debus O.1, Hütsch C.1, Dercks M.1, Fiedler B.2, Rödiger M.3,
Linden T.3, Omran H.3
1
Clemenshospital Münster, Klinik für Kinder- und
Jugendmedizin, Münster, Germany, 2Klinik für Kinder- und
Jugendmedizin, Universitätsklinikum Münster, Allgemeine
Pädiatrie, Bereich Neuropädiatrie, Münster, Germany,
3
Klinik für Kinder und Jugendmedizin, Allgemeine
Pädiatrie, UKM, Neuropädiatrie, Münster, Germany
In the estimation of the prognosis of traumatic brain injury mechanisms
of direct and indirect damage are believed to play an important role.
Axonal shearing injuries are meant to be crucial for a bad prognosis. This
mechanisms are seen for instance in older children with deceleration
accidents and in infants after shaking. Importantly, additional hypoxia
contributes to neurological deterioration. In our new department of
early pediatric neurological rehabilitation, children after traffic accidents with and without hypoxia and shaken infants were treated. A
qualitative analysis was performed regarding the consequences of the
different mechanisms of injury. Infants after shaking showed massive
bihemispheric destructions but good neurologic functions in the short
course, deteriorating after months into cerebral palsy or epileptic
encephalopathy. Older children with axonal trauma usually did not
develop cerebral atrophy and regained alertness rapidly with emerging
spasticity however. Children with hypoxia developed severe defect
syndromes ending in an apallic state. After traumatic brain injury
cerebral oxygenation must be the primary goal in the treatment of
these patients to minimize devastating neurological sequelae. Axonal
shearing might not disturb vigilance sustainably but influencing neuropsychological and motor skills and reintegration substantially. Correlation between mechanisms, localization, and quantity of the cerebral
injury detectable by magnetic resonance imaging and the extent of
motor and neuropsychological impairments can be quantified by higher
numbers of patients analyzed. This is one goal of the TBI-RegisterProject in North Rhine-Westphalia.
P014
Intestinal Pseudo-obstruction and Mydriasis As
Leading Symptoms for an Autonomic
Autoimmune Ganglioneuropathy
Debus O.1, Schlichtmann J.1, Candan H.1, Dercks M.1,
Hülskamp G.1, Küster P.1
1
Clemenshospital Münster, Klinik für Kinder- und
Jugendmedizin, Münster, Germany
Autonomic neuropathies are rare diseases in childhood. In general, the
course of these multisystem diseases is severe and long-lasting. Mostly,
postinfectious autoimmune reactions are believed to be etiologically
responsible. The diagnosis mostly is made by clinical and electrophysiological investigations. We present the case of a 12-year-old girl with
preexisting Asperger autism. At the time of admission, she suffered from
gastroenteritis and denial of food. After 2 days, she intermittently
developed a paralytic ileus and gastroparesis respectively with constipation and repeated vomiting. In addition, she developed urinary
retention, a subtotal mydriasis with no reactivity to light and reduced
tear production, a dry mouth, an irritation of taste, and anhidrosis.
Widespread diagnostics with ultrasound and magnetic resonance image
of the abdomen and head, a measurement of the transition time of the
colon, an electroencephalography, echocardiography, and an ophthalmological investigation revealed no further abnormalities. Antibodies
against gangliosides, ganglionic acetylcholine receptors, and toxicological and drug screens revealed were normal. Celiac antibodies or
abnormalities in CSF cytology, urine catecholamines, or microbiology
were not detected. Only motor nerve conduction velocity was lowered
whereas afferent signals were not detectable. Therapeutic trials with
neostigmine, pyridostigmine, immunoglobulins, and steroids did not
show significant effects. A supportive therapy including a suprapubic
urine catheter, fecal regulation, parental nutrition, and bifocal glasses
were necessary. The course was protracted over months and a therapy
with metronidazole was indicated due to intestinal bacterial proliferation. The urine catheter could be removed after 3 months, Broviac
catheter after 5 months. Mydriasis persisted as did the obstipation.
Neuropathic pain was successfully treated with pregabalin. Parainfectious autonomic autoimmune ganglioneuropathy is mainly diagnosed
on clinical grounds. Atonic bladder and gastrointestinal associated with
parasympatholytic symptoms should remind of this disease particularly
after unspecific infections. Electrophysiology can help detecting peripheral nerve involvement as can transmural bowel biopsy which is
dangerous in these circumstances however.
P015
Therapeutic Consequences of the Identification
of KNCQ2 Mutations in Early Onset Epileptic
Encephalopathy: A Case Report
Dietel T.1, Lerche H.2, Bast T.1
1
Epilepsiezentrum Kork, Kinderklinik, Kehl-Kork, Germany,
2
Universitätsklinikum Tübingen, Neurologische Klinik,
Tübingen, Germany
Early onset epileptic encephalopathy (EOEE) is characterized by pharmaco refractory seizures (including tonic spasms) starting in the first
weeks of life and typical electroencephalography pattern with suppression-burst and bilateral, multiregional epileptic discharges. The psychomotor development is severely impaired in most of the cases. Besides
structural lesions, variable genetic defects have been identified to be
potential etiologies. De novo mutations in KCNQ2 are a more frequent
etiology. Although up to 50% of the affected children may become
seizure free in the course, the psychomotor development remains
severely impaired. While only few patients seem to benefit from
retigabine, which directly acts on the KCNQ2 coded potassium channel,
many children seem to respond to classical sodium channel blockers. We
report the case of a 5-year-and-4-month-old girl with a severe form of
EOEE. Therapeutic trials with phenobarbital, topiramate, vigabatrin,
levetiracetam, sulthiame, valproate, clonazepam, and corticosteroids
failed to control the seizures. The etiology remained unclear although a
broad neurometabolic and genetic diagnostic work-up had been performed. At the age of 4.5 years, a molecular-genetic panel diagnosis
revealed a most probably pathogenic de novo mutation in KCNQ2
(c.659T>C; p.L220P, het.). The targeted use of retigabine (maximum
dose 8 mg/kg/d) was not effective. When oxcarbazepine (up to 20 mg/
kg/d) was added to valproate, levetiracetam, and vigabatrin, there was a
prompt and definite effect with a reduction of seizures by at least 75%,
especially of impairing tonic seizures even so valproate and vigabatrin
were stopped. As predicted by the physiologists, the indirect effect of
blocking sodium channels seems to be a stabilizing factor in relation to
the disturbed potassium flow. Sodium channel blockers are not a typical
therapy for early epileptic encephalopathies, and they may even aggravate seizures in these young infants. However, the administration is an
important therapeutic option in children with KCNQ2 mutations.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
investigations showed no pathological findings. Cranial magnetic resonance image (MRI) at day 4 showed basal accentuated meningeal
enhancement and restricted diffusion of the supratentorial brain. The
clinical course improved except for slight abducens nerve palsy. However, a second cranial MRI (day 16) showed a considerable increase of
the meningeal enhancement and repeated lumbar puncture showed a
continuing increase of protein level up to 2,990 mg/dL. Spine MRI now
showed considerable meningeal enhancement and a contrast-enhanced
intramedullary lesion at TH 10/11. CSF cytology showed repeatedly no
evidence of malignant cells. Additional investigations revealed no
evidence of tuberculosis, lues, cryptococcosis, cysticercosis, listeriosis,
Q fever, or sarcoidosis. Clinical deterioration with increasing signs of
intracranial pressure led to a meningeal biopsy at TH 2, which histologically showed a glioblastoma multiforme grade IV. Conclusion: Leptomeningeal tumor cell infiltration may present with symptoms of a
meningoencephalitis and strongly increased CSF protein level, mimicking infectious, or immune mediated disease. Confirmation of this
diagnosis might be possible only via biopsy.
S28
Abstracts
Munich, 17th to 19th September 2014
P016
Functional Movement Disorder in a Family with
PRRT2-Associated Paroxysmal Kinesigenic
Dyskinesia
Munich, 17th to 19th September 2014
Ebrahimi-Fakhari D.1, Kang K.1, Kotzaeridou U.1, SchubertBast S.1, Kohlhase J.2, Klein C.3, Assmann B.1
1
Zentrum für Kinder- und Jugendmedizin,
Universitätsklinikum Heidelberg, Sektion für
Neuropädiatrie, Heidelberg, Germany, 2Praxis für
Humangenetik Freiburg, Freiburg, Germany,
3
Universitätsklinikum Schleswig-Holstein Campus Lübeck,
Sektion für Klinische und Molekulare Neurogenetik, Lübeck,
Germany
Objective: This article aims to determine the etiology of an acute-onset
movement disorder in a 15-year-old girl with a family history of PRRT2associated paroxysmal kinesigenic dyskinesia (PKD). Methods: A combination of clinical characterization and longitudinal assessment, literature review, and genetic testing. Results: The patient presented with a
3-day history of recurrent episodes of abnormal movements. Her lower
limbs seemed predominantly affected, whereas her upper limbs and her
face were relatively spared. She retained awareness during the attacks
and described an aura of nonspecific discomfort precipitating her
abnormal movements. Family history was significant for classic PKD
in her brother and mother. On neurological examination, the movement
disorder was found to correlate with voluntary motor activity but was
not entirely paroxysmal in nature. When attempting to walk, increased
tone was observed in her limbs and trunk, without overt torsion or
dystonic posturing. She felt unable to walk without support. Her gait
showed features reminiscent of a cerebellar disorder, which may have
been mimicked by fluctuations in tone. Furthermore, her trunk showed
shaking movements, possibly consistent with hyperkinetic or “jerky”
dystonia. With ongoing motor activity, abnormal tone of her legs and
trunk increased to an extent that prevented her from moving forward.
The remainder of the examination was unremarkable. Laboratory
studies including CSF analysis, ECG, echocardiography, and an magnetic
resonance imaging scan of her brain and spine showed no abnormalities.
DNA sequencing of the coding exons and flanking introns of the PRRT2
gene revealed a heterozygous c.649dupC, pR217Pfs*8 mutation in exon
2 in all the three affected family members. In view of the family history
of classic PKD, the autosomal-dominant trait of this disease and the
presence of a PRRT2 mutation with confirmed pathogenicity, an atypical
presentation of PKD was considered. A trial of low-dosage oxcarbazepine (8 mg/kg/d) was given, leading to a complete resolution of
symptoms within days. Given the atypical clinical presentation, however, a functional movement disorder remained an important differential
diagnosis. To reinforce this hypothesis, therapy was discontinued after
16 months of complete remission. Symptoms did not return after a
follow-up of 8 months making a functional movement disorder the most
likely diagnosis. Conclusions: This case illustrates the diagnostic challenge in distinguishing an atypical phenotype presentation within the
growing spectrum of PRRT2-associated paroxysmal movement disorders in a family with genetically confirmed PRRT2-associated PKD. Our
report emphasizes the need to combine a thorough clinical diagnosis
and evaluation of secondary causes with the growing understanding of
the genetics behind complex monogenic movement disorders.
P017
Vomiting and Singultus As Presenting Signs and
Symptoms of Neuromyelitis Optica Spectrum
Disorder in a 14-Year-Old Boy
Egger S.1, Baumann M.2, Haberlandt E.2, Rostasy K.2
1
Department für Kinder- und Jugendheilkunde I,
Medizinische Universität Innsbruck, Innsbruck, Austria,
2
Division Neuropädiatrie, Department für Kinder- und
Jugendheilkunde I, Medizinische Universität Innsbruck,
Innsbruck, Austria
Background: Neuromyelitis optica (NMO) is a rare degenerative disorder of the central nervous system affecting mainly optic nerves and
spinal cord. It often leads to devastating visual and motor disabilities
with a 5-year mortality of 30%; so early recognition and treatment are
important. Obligatory criteria for diagnosis are transverse myelitis and
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
optic neuritis in the absence of defining criteria for multiple sclerosis
and ADEM. Aquaporin-4-receptor antibody seropositivity is diagnostic
as it has been detected exclusively in sera of patients with NMO and
neuromyelitis spectrum disorders (NMOSD). In children, presentation
may differ from adult onset NMO and is characterized by frequent brain
involvement. Case Report: The patient presented at the age of 14 years
with vomiting and singultus and was admitted several times for
vomiting and dehydration over a period of several weeks. On his third
admission, his neurological examination revealed peripheral left facial
paralysis, left-sided abducens nerve palsy, weakness of internal rotation
of the right eye, nystagmus, and impaired sensation on the left side of his
face. Magnetic resonance (MR) of the brain and the spinal cord showed
patchy T2 alterations of the corpus callosum, the area postrema, the
medulla oblongata on the left and in the spinocervical region. Investigations were normal for paired antibody titers for neurotropic viruses,
mycoplasma and Borrelia, lactate in serum and CSF, autoantibody
screening and isoelectric focusing of CSF. Initially, aquaporin-4-receptor
antibodies were absent. The patient was started on high-dose steroids
and all symptoms resolved. Hiccups and vomiting recurred after 6
months and after 7 months. On both occasions, there were no neurological abnormalities and MR of the brain and of the myelon was normal.
Aquaporin-4-receptor antibodies were now detestable in the serum.
Azathioprine was added in addition to oral prednisolone. Thereafter,
there were no more relapses and aquaporin-4-receptor antibodies were
not detectable any more. Conclusion: Hiccups and vomiting as presenting symptoms have occasionally been reported predominately in adult
NMO. Our report highlights that also children can be affected and early
recognition and treatment are important for outcome. All signs and
symptoms improved weeks after onset of treatment with steroids and
Azathioprine. Follow-up so far has yielded normal clinical results.
Vomiting and singultus are common in childhood, if they persist,
consideration of NMO is important in order not to miss potentially
lifesaving early treatment.
P018
Cerebral Artery Dissection in Pediatric Patients:
Lessons from Clinical Practice
Eickholt C.1, Valcheva D.1, Mangold A.2, Rosenbaum T.1
1
Klinikum Duisburg GmbH, Klinik für Kinder- und
Jugendmedizin, Duisburg, Germany, 2Klinikum Duisburg
GmbH, Klinik für Radiologie und Neuroradiologie,
Duisburg, Germany
Background: Stroke is a rare yet frequently underestimated event in
pediatric patients, occurring in 3 to 5 of 100,000 individuals per year.
Common etiologies include infections, trauma, cervical manipulations,
homocysteinemia, migraine, as well as skeletal, and vascular malformations. Another typical mechanism is cerebral artery dissection (CAD),
accounting for 25% of pediatric stroke patients. While difficult to assess
by nonenhanced CT scan, CAD can be detected by magnetic resonance
imaging (MRI). Methods: Patients presenting to our facility between
November 2011 and December 2013 with signs of cerebral ischemia
were retrospectively analyzed. All patients received complete diagnostic
work-up including CT imaging, MRI, and MR angiography. Results: We
herein report three female pediatric patients (age, 9.0 $ 2.1 years)
presenting with neurological symptoms suggestive of cerebral ischemia
(brachiofacial hemiparesis, motor and coordinative deficits, and dysarthria). In two cases, there was a preceding minor traumatic event, in one
case no trauma occurred. Initial CT imaging ruled out any skeletal
injuries and in two patients, revealed evidence of cerebral ischemia.
One diagnosis of CAD could be confirmed already at this stage. In
another case, no signs of cerebral ischemia or vascular lesions were
present. In addition, MRI revealed the presence of CAD in all patients,
originating in the arteria carotis interna at the level of the processus
clinoideus anterior and extending into the arteria cerebri media (M1
segment), respectively. This observation is in contrast to data from adult
patients, who typically present with an extracranial location of the
lesion. There also was no evidence of intramural hematoma. All patients
showed a surprisingly similar distribution of cerebral infarction in the
basal ganglia, explainable by a disruption of the lenticulostriate arteries
due to shearing of the vessel wall in the M1-segment of the middle
cerebral artery. Conclusions: CAD in pediatric patients is a rare, yet
Abstracts
S29
Munich, 17th to 19th September 2014
serious event. Because of its atypical presentation and difficult recognition in CT imaging, MRI should be the gold standard for diagnosis.
Presence of an intravascular dissection membrane, absence of intramural hematoma and intracranial origin of the lesion are distinct characteristics of pediatric CAD. Development of guidelines for diagnostic workup will improve discovery rates in clinical practice and thus ensure its
timely and adequate treatment.
Ensslen M.1, Menzies L.1, Borggraefe I.2, Heinen F.2, Moeller
F.1, Boyd S.1, Pressler R.1
1
Great Ormond Street Hospital for Children,
Neurophysiology, London, United Kingdom, 2Kinderklinik
und Kinderpoliklinik im Dr. von Haunerschen Kinderspital,
Neuropaediatrie, Muenchen, Germany
Aim: Reliable classification of neonatal seizures remains controversial,
but it is a key tool for research and clinical purposes. Currently used
classification systems include the one proposed by Volpe (1989; 2001)
with an emphasis on clinical criteria, the one proposed by Mizrahi and
Kellaway (1987, 1998) including electrographic seizures and the one
suggested in the ILAE revised seizure terminology by Berg et al (2010) as
part of an overall seizure classification system not considering specific
neonatal seizure patterns. In this study, we evaluate these classification
systems on the basis of a retrospective analysis. Methods: Neonates
treated at Great Ormond Street Hospital, London, United Kingdom, a
tertiary medical center, with seizures captured on video-electroencephalography (EEG) were included if recorded before 28 days of age in term
infants or before 44 weeks postconceptional age in premature infants.
Recordings were assessed for seizure frequency, duration, and grouped
into the following: (1) electroclinical, (2) electrographic, and (3) clinical
only. The three current classification systems were used to characterize
seizures and their accuracy was assessed (where available demographic
data were collected regarding comorbidities, current medications, and
seizure etiology). Results: We identified 85 neonates with seizures
recorded on video-EEG from 2005 to 2014 (mean chronological age 15
days; range, 1-53 days) including 21 preterm infants (mean gestational
age at recording 28 weeks; range, 30-43 weeks). Average seizure burden
was 428 s/h. We identified 268 events consisting of 151 (56%) electrographic seizures, 80 (30%) electroclinical seizures, and 37 (14%) clinicalonly seizures. Of the 56 newborns with electrographic seizures, 46 had
only electrographic events. Mean duration was 114 seconds for electroclinical seizures and 129 seconds for electrographic seizures. In the
Volpe classification, 32% of the events were fully classifiable and 18%
were partly classifiable, in the Mizrahi and Kellaway classification 26% of
the events were fully classifiable and 76% were partly classifiable, and in
the ILAE classification 21% were fully classifiable and 18% were partly
classifiable. Conclusion: Neonatal seizures were often electrographic
and showed a considerable duration, which supports the importance of
video-EEG monitoring in neonatal intensive care. A large number of
neonates presented without associated clinical seizures and would
otherwise be missed. All three classification systems could fully classify
only up to one-third of the seizures. Overall, the high proportion of
electrographic seizures, the complex seizure semiology and the subtle
seizure manifestations in neonates contributed to this result. Therefore,
we feel the necessity of a distinct classification system in the neonatal
period, which should be based on electroclinical phenotypes and ideally,
reflect pathophysiologic origin.
Faltermeier K.1, Reiter M.2, Hasse A.1, Wimmer C.3, Rosner
V.1, Berweck S.1
1
Schön Klinik Vogtareuth, Neuropädiatrie, Vogtareuth,
Germany, 2Sanitätshaus Spörer, Vogtareuth, Germany,
3
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurologische Rehabilitation, Epilepsiezentrum für Kinder
und Jugendliche, Vogtareuth, Germany
Question: Does a new adjuvant prove its worth to correct malposition of
extremities and hypotonia of the body in the praxis of pediatric neurorehabilitation? Material: TheraTogsTM (Telluride, Colorado, United
States) is an adjuvant which consists of trousers, waistcoat, and diverse
applications that can also be worn separately. It is made of a special
fabric which is worn directly on the skin. By proprioception, pull and
stabilization, malpositions can be corrected and biomechanic conditions
can be optimized. So far, 19 children from toddler to adolescent age were
supplied with TheraTogs. Result: A total of 12 children received a body, 7
on application for arm and hand. The body served for erection and
stabilization of the body because of hypotonia. The applications for the
upper extremity served for support of supination, wrist extension, and
thumb abduction. We found positive effects of different intensity,
especially in combination with other procedures, for example, physiotherapy and botulinum toxin. Benefits: The fabric is worn under the
normal clothing and does not attract much attention. Special clothes or
shoes are not necessary. By diverse applications that can be used or left
an individual adjustment is possible. The material is light and flexible.
Disadvantages: The dressing can be challenging and associated with
expenditure of time according to the number of applications and
cooperation of the patient. The material is not breathable and warm
in summer. Limits of the method: Serious malpositions cannot be
corrected because the firmness and the effect of correction do not
suffice. Conclusion: TheraTogs is a new aids material and therapy
concept for correction of body hypotonia and moderate malposition
of extremities. The fabric can be arranged between pure proprioceptive
bandages and firm cotton fabrics with elastic elements. The utilization
requires training and time.
P021
Two Faces of Genetic Epilepsy Caused by a
Mutation in the SCN8A Gene
Fazeli W.1, Neu A.1, Wenner K.2, Wickert J.3, Johannsen J.2,
Santer R.4, Denecke J.2
1
Universitätsklinikum Hamburg-Eppendorf, AG
Experimentelle Neuropädiatrie, Zentrum für Molekulare
Neurobiologie Hamburg, Hamburg, Germany,
2
Universitätsklinikum Hamburg-Eppendorf, Klinik für
Kinder- und Jugendmedizin, Neuropädiatrie, Hamburg,
Germany, 3Institut für Humangenetik,
Universitätsklinikum Hamburg-Eppendorf, Hamburg,
Germany, 4Universitätsklinikum Hamburg-Eppendorf,
Klinik für Kinder- und Jugendmedizin, Hamburg, Germany
Introduction: Mutations of genes that encode for cerebral sodium
channels are associated with epilepsy of variant severity. Mutations of
the SCN8A gene encoding the cerebral sodium channel Nav1.6 have so far
been rarely described. Patients: After an uneventful pregnancy, patient
A was spontaneously born at term, then showing respiratory distress
and hyperexcitability. During the 4th week of life, first generalized tonic
seizures occurred which could not be explained though extensive
diagnostic tests were performed. At first, seizures were well controlled
under anticonvulsant treatment with oxcarbazepine. However, tonicclonic seizures developed. They became therapy-resistant during the
following months. Other antiepileptic drugs such as topiramate, valproic
acid, vigabatrin, lamotrigin, high-dosage cortison, and ketogenic diet
were all unable to control seizures. The patient finally developed an
epileptic encephalopathy with severe psychomotor delay and clusterlike occurrence of tonic-clonic seizures. Furthermore, she repeatedly
developed fractures of so far unknown origin. Patient B developed
normally until her first tonic seizure at 6 months of age. As electroencephalography and psychomotor development remained normal,
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
P019
Neonatal Seizures: Evaluation of Current
Classification Systems
P020
Possible Applications for TheraTogs in Pediatric
Neurorehabilitation
S30
Abstracts
Munich, 17th to 19th September 2014
Munich, 17th to 19th September 2014
Watanabe-epilepsy was suspected. During the following months
though, she displayed several episodes with up to 20 tonic-clonic
seizures per day. In between these episodes, she showed normal
behavior and was still not impaired in her development. Treatment
with sultiam, oxcarbazepine, levetiracetam, and lamotrigin did not
influence the occurrence of seizures. Result: Both patients finally
showed distinct de novo mutations of the SCN8A gene, presumably
explaining the earlier described phenotype. Conclusion: SCN8A encodes
for the cerebral sodium channel Nav1.6; mutations in the SCN8A gene
have previously been associated to epilepsy. We describe two female
patients with SCN8A mutations presenting completely different phenotypes. We are currently investigating how the Nav1.6 activity is
changed in both patients and whether this can possibly explain the
difference between the phenotypes.
P022
Ambulatory Neuropediatrics in Germany 2013
to 2014: Where, What, and How Much?
Fehr F.1
1
Gemeinschaftspraxis für Kinder und Jugendliche,
Schwerpunkt Neuropädiatrie, Sinsheim an der Elsenz,
Germany
What are the current and future needs of neurological ill children and
adolescents in Germany in the ambulatory sector? To determine this
need, the Working Group of Ambulatory Neuropediatrics (AG NNP)
issued a survey in 2013 to determine the work load and diagnostic and
therapeutic spectrum of over 150 ambulatory working neuropediatricians in Germany. The survey is continued in 2014 to account for the
demographic development to extrapolate trends for the future. Besides
a precise description of the ambulatory neuropediatric performance this
survey allows for conclusions as, for example, the differences in diagnostic and therapeutic spectra across Germany. It becomes clear that the
care for children and adolescents with chronic headache, behavioral
problems, and paroxysms is primarily organized ambulatory. Those
patients do not usually frequent highly specialized hospitals where the
majority of the neuropediatricians to be are trained. This finding poses
questions concerning neuropediatric postgraduate education in terms
of power, identity, and location of our future colleagues.
P023
A Nonclassical Clinical Course of Barth
Syndrome
Fleger M.1, Huemer M.1, Mayr J.2, Sperl W.2, Prokisch H.3,
Haack T.3, Bowron A.4, Huemer C.1, Schlachter K.1
1
Kinder- und Jugendheilkunde, LKH-Bregenz, Austria,
2
Universitätsklinik für Kinder- und Jugendheilkunde
Salzburg, Austria, 3Institut für Humangenetik TU München,
Germany, 4University Hospitals, Bristol, United Kingdom
A 6-year-old boy of Roma decent, born to nonconsanguineous, healthy
parents was primarily referred because of growth retardation. Auxological parameters were below the 3rd percentile after having been
normal at birth. The 3rd percentile had been crossed at age 12 months,
without any catch-up growth afterward. Especially, the extent of
microcephaly (< 3 standard deviation) was impressive. In addition,
mild generalized muscular hypotonia was present. Psychomotor development was regular. Gastrointestinal, endocrinological, and nutritional
work-up revealed no explanatory pathological findings. Metabolic
work-up including lactate profile, pyruvate and lactate/pyruvate ratio,
urinary organic acids, plasma amino acid profile, ammonia, creatine
kinase, total and free carnitine, and acylcarnitine profile was normal.
Magnetic resonance imaging (MRI) of the brain and MR spectroscopy
showed no pathologies. Overall, 18 months later, the patient presented
with episodes of painless muscular weakness and severe exercise
intolerance triggered by a febrile infection. Clinical findings included
muscular weakness, hypotonia, and positive Gower’s sign in the absence
of muscular atrophy. Diagnostic work-up again revealed normal values
for creatine kinase, ASAT, ALAT, and metabolic parameters. Myosonography was unremarkable. The combination of unclear muscular symptoms and persistent growth retardation prompted mitochondrial workup. A muscle biopsy from m. rectus femoris revealed reduced activity of
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
complex I, III, and IV in oxidative phosphorylation. Whole exome
sequencing revealed the mutation c.281G>A (p.Arg94His) in the tafazzin gene (NM_000116). This mutation has been described as associated
with early onset, severe Barth syndrome.1 The diagnosis of Barth was
supported by a specific pattern of fatty acid profile of cardiolipin.
Nevertheless, characteristic signs and symptoms for Barth syndrome
such as cardiomyopathy, neutropenia, or 3-methylglutaconic aciduria
have never been observed in the patient. At the age of 10 years, the
patient shows persistent growth retardation and very mild exercise
intolerance. Echocardiography and white blood cell counts as well as
psychomotor development are persistently normal for age.
Reference
1 Brady AN, Shehata BM, Fernhoff PM. X-linked fetal cardiomyopathy
caused by a novel mutation in the TAZ gene. Prenat Diagn 2006;26
(5):462–465
P024
Human Parechovirus Encephalitis As an
Important Differential Diagnosis of White
Matter Lesions in Neonatal Sepsis-Like Illness
Freudenberg L.1, Brenner S.2, Hahn G.3, van der Knaap M.4,
Smitka M.1, von der Hagen M.1
1
Department of Child Neurology, Children’s Hospital,
Technical University, Dresden, Germany, 2Pediatric
Intensive Care Unit, Children’s Hospital, Technical
University, Dresden, Germany, 3Section of Pediatric
Radiology, Department of Radiology, Technical University,
Dresden, Germany, 4VU University Medical Center,
Amsterdam, The Netherlands
Human parechoviruses (HPeVs) are a family of neurotropic viruses that
may cause central nervous system () infection in the neonatal period,
resulting in white matter lesions with a large spectrum of neurological
symptoms. Common clinical presentations of infections with HPeV type
3 (HPeV3) are seizures, apnea, irritability, and lethargy. We report on a
case of neonatal HPeV encephalitis, diagnosed on the basis of magnetic
resonance image (MRI) findings and HPeV3 polymerase chain reaction
(PCR). At the age of 4 weeks, the previously healthy infant presented
with recurrent severe apnea, lethargy, and mild diarrhea. The child was
irritable with the clinical symptoms of a sepsis-like neonatal infection,
requiring mechanical ventilation for 7 days. Diagnostic work-up with Creactive protein, enterovirus PCR, and metabolic tests revealed no
abnormalities. CSF protein levels were elevated. MRI at the fourth day
of illness revealed diffuse signal intensity changes of the white matter
with multiple punctate lesions. The diffusion-weighted images showed
areas of restricted diffusion in the periventricular and subcortical white
matter, in particular, the frontal white matter, but also the corpus
callosum, internal capsule, part of the thalamus, and pyramidal tracts
of the brain stem without enhancement after contrast. The pattern of
MRI involvement was suggestive of parechovirus encephalitis. HPeV3
PCR was positive in nasopharyngeal swap and stool samples. The infant
gradually improved and was discharged on day 18, but developed
hemiparesis with a lower limb predominance. HPeV3 should be suspected in neonates with clinical presentation of sepsis-like illness,
apnoe, and CNS involvement and tested negative for enteroviruses.
P025
Spinal Cord Infarction: A Rare Case of
Neurological Sequeale of Lupus Erythematodes
Gaiser U.1, Krägeloh-Mann I.1, Nägele T.2, Schöning M.1,
Alber M.1, Moll M.3
1
Universitätsklinikum Tübingen, Neuropädiatrie,
Entwicklungsneurologie, Sozialpädiatrie, Tübingen,
Germany, 2Universitätsklinik Tübingen, Neuroradiologie,
Tübingen, Germany, 3Universitätkinderklinik Tübingen,
Rheumatologie, Tübingen, Germany
Background: Infarction of the spinal cord is rare compared with cerebral
infarction. Spinal cord infarction is most frequently caused by surgical
Abstracts
S31
Munich, 17th to 19th September 2014
P026
PARADIGMS: Fingolimod in Children and
Adolescents with MS
Gärtner J.1, Chitnis T.2, Banwell B.3, Karlsson G.4, Karan R.4,
Merschhemke M.4, Putzki N.4, Li B.5, Griese B.6, Vormfelde S.6
1
Neuropädiatrie, Universitätsmedizin Göttingen,
Göttingen, Germany, 2Massachusetts General Hospital,
Partners Pediatric Multiple Sclerosis Center, Boston,
Massachusetts, United States, 3Division of Neurology, The
Children's Hospital of Philadelphia, Philadelphia, United
States, 4Novartis Pharma AG, Basel, Switzerland, 5Novartis
Pharmaceuticals Corporation, East Hannover, New Jersey,
United States, 6Novartis Pharma GmbH, Nürnberg,
Germany
Disclosure: These results have been presented at the congress of the
American Academy of Neurology 2014 (April 26, 2014-May 3, 2014,
Philadelphia, United States). Background: Fingolimod has been approved in over 70 countries for the treatment of adult MS patients
over 18 years of age with relapsing remitting MS (RRMS). In adults,
fingolimod is more effective than interferon β-1a intramuscular. In 5% of
all cases, MS is diagnosed during childhood or adolescence younger than
18 years. To date, there is no controlled clinical study on the effectiveness or safety of a disease-modifying treatment in these patients.
Fingolimod is more effective in young adults with MS than in older
patients. Thus, it may be anticipated that fingolimod in children and
adolescents with RRMS will be at least as effective. Objective: This
article aims to describe the design of the PARADIGMS study on fingolimod in children and adolescents with RRMS. Design/Methods: PARADIGMS compares oral fingolimod with interferon β 1a intramuscularly
in children and adolescents. PARADIGMS is designed as a multinational,
2-year, double-blind, randomized controlled clinical trial. It shall include 190 boys and girls worldwide aged 10 to 17 years with at least on
recent relapse. They will be 1:1 randomized to oral fingolimod 0.5 mg
once daily (0.25 mg with body weight of 40 kg or less) or intramuscularly
injected interferon β 1a (Avonex; Biogen Idec Inc., Cambridge, MA,
United States) 30 µg once weekly. In addition, in the fingolimod arm,
the study patients will inject weekly placebo and take an oral placebo
daily in the interferon arm, respectively (“double-dummy” design).
Primary PARADIGMS end point is the annual relapse rate. Prominent
secondary end points comprise brain volume and cognition.
Conclusions: PARADIGMS will demonstrate whether and how good
the fingolimod will help children with RRMS.
P027
Spinocerebellar Ataxia: Finding the Diagnosis
with Whole Exome Sequencing
Geldner J.1, Schmidt W.2, Bittner R.2, Bernert G.1
1
G.v.Preyer'sches Kinderspital, Wien, Austria,
2
Neuromuscular Research Department, Medical University
of Vienna, Wien, Austria
Spinocerebellar ataxias are a group of clinically rather similar, but
genetically very heterogeneous illnesses (currently more than 30 genes
causing these ataxias are known). Because no clear phenotype-genotype correlation exists, associated symptoms such as cognitive deficits,
epilepsy, oculomotor disturbances, or peripheral neuropathies do not
really help to find the right diagnosis. Therefore, the way from the
suspicion of a spinocerebellar ataxia to the confirmation by a genetic
finding is often long and expensive. We present a case of a 17-year-old
Turkish patient with consanguineous parents and a family history of
epilepsy in the sister and migraine in both mother and sister. The child
had difficulties with target-oriented movements starting when she was
6 years. At the age of9 years, she started to fall down repeatedly and was
brought to our outpatient clinic. She presented with an ataxia. Electroencephalography (EEG) was abnormal, but all the other investigations,
including magnetic resonance imaging (MRI) and nerve conduction
tests were normal. In the last years, the ataxia was mildly progressive
and the speech increasingly dysarthric. Under antiepileptic treatment,
she was seizure free, even though the EEG stayed abnormal. Repeated
MRIs and nerve velocity investigations were always normal. We performed a whole-exome sequencing, which led to the finding of two,
until now, unknown mutations in two known spinocerebellar ataxia
genes (CACNA1A and TGM 6). To evaluate the potential pathogenicity of
detected mutations, segregation analysis is currently performed. The
results of this analysis will be presented at the congress in Munich.
P028
Hearing Loss, Growth, and Gait Disturbance:
The Diagnostic Struggle of Neuroborreliosis
Gerstl L.1, Berweck S.2, Hübner J.3, Heinen F.1, Borggräfe I.1
1
Dr. von Haunersches Kinderpsital, Ludwig-MaximiliansUniversität München, Pädiatrische Neurologie,
Entwicklungsneurologie und Sozialpädiatrie, iSPZ,
München, Germany, 2Schön Klinik Vogtareuth,
Neuropädiatrie, Vogtareuth, Germany, 3Dr. von
Haunersches Kinderspital, Ludwig-MaximiliansUniversität München, Abteilung für Infektiologie, München,
Germany
Neuroborreliosis in childhood mostly presents as meningitis with
lymphocytic pleocytosis in the cerebrospinal fluid and facial nerve
palsy. We report two cases with unusual clinical presentation and
course. Case 1: A 13-year-old boy presented with growth retardation,
progressive hearing loss over 3 years and gait disturbance. Gadoliniumcontrasted magnetic resonance imaging (MRI) showed enhancement of
basal meninges, vestibulocochlear nerve, caudal cranial nerves, and the
whole spinal cord. Cerebrospinal fluid revealed lymphocytic pleocytosis, an increased protein concentration and a lowered glucose level. The
presence of an elevated Borrelia burgdorferi IgG CSF/serum index,
specific Borrelia burgdorferi IgM antibodies and elevated concentration
of the chemokine CXCL13 in cerebrospinal fluid confirmed the diagnosis
of chronic neuroborreliosis. A 3-week intravenous antibiotic therapy
leads to a slight improvement of his gait. Actually, complete growth
hormone deficiency and functional deafness require growth hormone
substitution and cochlear implantation. Case 2: A 3-year-old boy was
admitted to the hospital and presenting with weakness of hips and
legs—he was unable to walk alone. The performed spinal MRI showed a
significant postcontrast enhancement of the nerve roots from the 11th
thoracic vertebra to the first lumbar vertebra. Findings of the cerebrospinal fluid—lymphocytic pleocytosis, elevated protein concentration,
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
procedures, pathologies affecting the aorta or trauma. Other causes of
spinal cord infarction are diverse (infectious, neoplastic, vascular,
autoimmune, and hereditary degenerative disorders). Case Report: A
16-year-old otherwise healthy girl presented with acute paraplegia;
onset was at night and development rapid (< 2 hours). Trauma was not
reported. The initial magnetic resonance imaging (MRI) showed focal
hyperintensity in rostral myelin regions (cervical vertebra C5/C6). CSF
showed both elevated IgG and cell count. Under treatment with high
dose prednisolone paraparesis remained unchanged. MRI at follow-up
demonstrated a T2-signal change consistent with cord ischemia. In the
following days, the girl developed vasculitis spots on both hands.
Laboratory results showed leukopenia, elevated antinuclear antibodies,
as well as antiphospholipid-antibodies. The skin biopsy showed lupus
band in immunofluorescence. Whole body MRI showed several spots of
myositis. As ACR criteria for lupus erythematodes were fulfilled, we
started treatment with immunoglobulin and plasmapheresis and cyclophosphamide. Long-term cortisone and hydroxychloroquine treatment was started. Unfortunately, several weeks’ later severe pain
developed in the lower extremities. Whole body MRI control showed
increase of myositis changes. Muscle biopsy showed myopathic changes
without signs of inflammation consistent with to cortisone myopathy.
Cortisone was discontinued. The pain and MRI changes resolved over
time. The patient remained fully paraplegic for nearly 4 months, and
then motor function of the lower extremities slightly improved. She
continued with intensive physiotherapy and hydroxychloroquine medication for 4 years, and showed continuous improvement during the
past 3 years. She is now able to stand and walk a few steps with
assistance. Conclusion: Spinal cord infarction is a rare condition caused by
a wide range of pathologic conditions. Lupus erythematodes, especially in
younger patients, is a rare cause. The severity can vary. Permanent and
disabling neurologic deficits remain in most patients. Our patient demonstrates that though improvement is possible over a long period of time.
S32
Abstracts
Munich, 17th to 19th September 2014
low glucose level, elevated concentration for the chemokine CXCL13,
elevated Borrelia burgdorferi IgG CSF/serum index—leaded to the
diagnosis of neuroborreliosis. Intravenous antibiotic therapy achieved
gait improvement in a short-time follow-up. Clinical recovery went
along with a normalization of CXCL13 concentration in cerebrospinal
fluid. Conclusion: Uncommon clinical presentations of neuroborreliosis
can lead to a significant delay in diagnosis and therapy and thereby
sometimes to permanent disability. CXCL13 in cerebrospinal fluid can be
used as additional biomarker in the diagnosis of neuroborreliosis as well
as in the monitoring of therapeutic success.
Munich, 17th to 19th September 2014
P029
Diffusion Tensor Imaging and Tractography
Identify Structural Changes in 14-Year-Old
Patient with Cryptogenic Focal Epilepsy
Goc J.1, Borggräfe I.2, Noachtar S.3, Vollmar C.4
1
Klinikum Grosshadern, Neurology, Epilepsy Centre,
Muenchen, Germany, 2Dr. von Haunersches Kinderspital,
LMU Muenchen, Neuropaediatrie, Muenchen, Germany,
3
Klinikum der Universität München ‐ Großhadern, LudwigMaximilians-Universität, Interdisziplinäres
Epilepsiezentrum, Neurologische Klinik und Poliklinik,
München, Germany, 4Klinikum der Universität München,
Neurologische Klinik, Epilepsie-Zentrum, München,
Germany
Background: A 14-year-old boy presented with a history of mostly
nocturnal seizures since the age of 8 years, pharmacoresistant to
multiple antiepileptic drugs including valproate, oxcarbazepine, levetiracetam, topiramate, and sultiam. Video-electroencephalography
(EEG)-monitoring recorded 22 brief bilateral tonic seizures in 3 days.
The patient reported that seizures from wakefulness were often preceded by somatosensory aura of the left hand. The interictal EEG showed
right central and temporal spikes (80%), as well as left central spikes
(20%). Ictal EEG demonstrated nonlateralized or right frontal seizure
pattern, sometimes followed by right postictal slowing. Ictal SPECT
indicated a right hemispheric hyperperfusion, but conventional magnetic resonance imaging (MRI) at 3T failed to show any structural
abnormalities. Methods: Diffusion tensor imaging (DTI) data were
acquired on a GE Signa HDx 3T Scanner (General Electric, Milwaukee,
WI, United States), using an acquisition scheme with 64 diffusion
weighted directions, a b value of 1,000 s/mm2, 2.4-mm slice thickness,
and 2 mm in-plane resolution. After preprocessing and tensor fitting,
streamline tractography of the whole brain was performed. Fiber
density images were reconstructed and quantitatively compared against
a control population of 18 healthy subjects. Regions of statistically
significant reduction of fiber density were identified, using a fully
automated processing pipeline. Results: The patient showed a significant decrease in U-fiber density in the right temporoparietal region,
most pronounced in the right somatosensory cortex. This finding
correlates with the clinical hypothesis of a right hemispheric seizure
onset. While the predominant tonic seizures indicate a symptomatogenic zone in the frontal lobe, the preceding somatosensory aura with
tingling sensation in the left hand strongly indicates a parietal seizure
onset, followed by fast propagation to the frontal lobe. Conclusion: This
case shows the potential role of DTI and tractography as complementary
lateralizing and localizing imaging modality in the presurgical evaluation of cryptogenic focal epilepsy in pediatric patients. The absence of a
structural lesion in conventional MRI is typically associated with
reduced chances for seizure free outcome, raising the threshold for
surgical treatment in such patients. The new DTI-based analysis presented here can identify previously undetected structural abnormalities, guiding further invasive evaluation and facilitating access to
epilepsy surgery in children with medically refractory focal epilepsy.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
P030
Early Onset Hereditary Spastic Paraplegia in
Childhood: A Remarkable Differential Diagnosis
in Children with Gait Problems
Goerg M.1, Kurth I.2, Geisendorf S.1, Stenzel M.3, Brandl U.1
1
Universitätsklinikum Jena, Neuropädiatrie, Jena,
Germany, 2Institut für Humangenetik, Jena, Germany,
3
Institut für Interventionelle und Diagnostische Radiologie,
Universitätsklinikum Jena, Sektion für Pädiatrische
Radiologie, Jena, Germany
Introduction: Gait disturbances are one of the most frequent reasons to
refer a patient for further neuropediatric investigation. Differential
diagnosis varies from CP, muscle and metabolic disorders to habitual
toe walking. We report another rare cause of gait disturbances, which
should always be kept in consideration. Case Report: A 3-year-old boy
was referred to our outpatient clinic for further investigation of gait
disturbances and reduced resilience during exercise noticed from 18
months of age. Pregnancy and birth history were uneventful with no
indication of intrauterine or perinatal hypoxia or asphyxia. Early motor
milestones were achieved within the normal timeframe. From the age of
18 months, a significant discrepancy of the boy’s gait, strength and
endurance compared with his peers in kindergarten were noted. He
showed a tendency to fall and could not keep up with the other kids
during exercise. Initially, the boy presented with muscular hypotonia
and weakness, a slow and clumsy gait with a broad base and ataxic
appearance, Gower sign was positive. Extensive clinical, laboratory, and
imaging studies did not elicit any abnormality. Over the course of
following year, his clinical situation deteriorated and signs of spasticity
became apparent while cranial magnetic resonance imaging (MRI)
remained unremarkable. Gait analysis showed a pattern similar to
bilateral spastic hemiplegia left greater than right with premature
muscle activation in swing and stance. Because of a family history of
a grandfather and great-grandmother on the maternal side with an early
onset of a foot deformity and despite a healthy mother and older sister,
genetic testing for autosomal-dominant hereditary spastic paraplegia
was initiated and confirmed a heterozygote missense mutation in the
ATL 1 gene (c.1483C>T, p.Arg495Trp). The mutation has previously been
reported in independent families with early-onset spastic paraplegia.
Conclusion: Hereditary spastic paraplegia is a rare, but important
differential diagnosis for children presenting with gait disturbances
and sign of spasticity similar to bilateral hemiplegia and normal MRI.
P031
Microduplication Syndrome 20q11.21q12: A
First German Case
Goerg M.1, Mrasek K.2, Weise A.2, Vilser D.3, Husain R.1,
Brandl U.1
1
Universität Jena, Klinik für Kinder- und Jugendmedizin,
Neuropädiatrie, Jena, Germany, 2Institut für
Humangenetik, Universitätsklinikum Jena, Jena, Germany,
3
Sektion für Kinderkardiologie, Klinik für Kinder- und
Jugendmedizin Universitätsklinikum Jena, Jena, Germany
Case Report: We report a now 9-month-old boy born to a healthy
nonconsanguineous couple presenting with marked muscular hypertonia
at birth, small for gestational age, and multiple dysmorphic features such as
single transverse palmar crease, low set ears, epicanthus, hypertelorism,
and flattened philtrum. Cardiac ultrasound showed a muscular VSD and
postductal stenosis of the aorta, without hemodynamic impact. By the age
of 3 months, the patient first presented to our neuropediatric outpatient
clinic for follow-up. Along with the dysmorphic features already present
at birth, his head circumference had stayed below the 3rd percentile
with the occipital bone being severely flattened, the neck appeared
broadened and the metopic ridge prominent. Muscle tone was still
hypertonic with ophisthotone posturing. Eye movements showed a
slight nystagmus and despite the general hypertonia he showed severe
head lag on traction. In later follow-up, appointments ongoing decrease
in muscle tone and a slow progress in motor development following
regular physiotherapy were observed. Genetic testing with cytogenetic
chromosome and fluorescence in situ hybridization analysis as well as
array comparative genomic hybridization was initiated, showing 10.5
Mb duplication in 20q11.21q12 inserted into 5q14.3!15 and a 138 kb
Abstracts
S33
Munich, 17th to 19th September 2014
duplication in Xp11.4. Conclusion: Microduplication syndrome
20q11.21q12 is associated with trigonocephaly, developmental delay,
and facial dysmorphism as present in our patient. The impact of the
small duplication in Xp11.4 is yet not clearly predictable.
P032
Goerg M.1, Schreyer I.2, Mrasek K.2, Weise A.2, Vilser D.3,
Stenzel M.4, Skirl G.1, Brandl U.1
1
Neuropädiatrie, Universitätsklinikum Jena, Jena,
Germany, 2Institut für Humangenetik,
Universitätsklinikum Jena, Jena, Germany,
3
Universitätsklinikum Jena, Klinik für Kinder- und
Jugendmedizin, Sektion für Kinderkardiologie, Jena,
Germany, 4Institut für Interventionelle und Diagnostische
Radiologie, Universitätsklinikum Jena, Sektion für
Pädiatrische Radiologie, Jena, Germany
Case Report: The girl was born to healthy, nonconsanguineous parents.
Ultrasound scan at 20 weeks of gestation suggested the existence of
ventriculomegaly and an occipital meningocele as well as multiple
ventricular septum defects. Subsequently, a fetal magnetic resonance
imaging (MRI) was preformed, confirming the brain and heart malformations. Zytogenetic chromosomal analysis of chorionic villus samples
showed 46, XX. The child was born at 38 weeks of gestation, presenting
with a small soft occipital bulging of the skin, retrognathia, and mild
respiratory distress requiring continuous positive airway pressure
ventilation. High-pitched cry was noticed in the first weeks of life.
Cranial MRI during postnatal care showed ventriculomegaly, a midline
cyst, megacisterna magna with a communicating occipital meningocele.
ECHO confirmed multiple ventricular septum defects without hemodynamic impact. The girl was followed up for head ultrasound scans on a
regular basis and first presented at the age of 3 months to our neuropediatric outpatient clinic with severe developmental delay. To define
an overriding syndrome to explain the clinical condition, genetic testing
was initiated. Array comparative genomic hybridization and FISH
analysis revealed an unbalanced translocation t(5;20) leading to a
deletion of 5p15.33p15.2 and a duplication in 20q13.2q13.33. Furthermore, a deletion in 4p16.2 was demonstrated. The translocation proved
not to be detectable by cytogenetic chromosome analysis due to the
similar size and appearance in GTG banding. Conclusion: Our patient
shows a combination of Cri du chat syndrome and duplication of
20q13.2q13.33. Both have been characterized by microcephaly, facial
dysmorphism, brain malformations, hypotonia, and severe psychomotor and mental retardation. The impact of the deletion in 4q16.2 on our
patient is yet unpredictable, as only mutations in 4q16.2 have been
reported to cause Ellis-van-Creveld or Weyers acrodental dysostosis.
P033
Rhabdomyolysis without Hemolytic Crisis in a
Juvenile Patient with Glucose-6-Phosphate
Dehydrogenase Deficiency
Gruber-Sedlmayr U.1, Brunner-Krainz M.1, Schwerin-Nagel
A.1, Kortschak A.1, Haber E.2, Zhumakhanov D.3, Schmidt
W.4, Bittner R.4, Muntean W.1
1
Universitätsklinik für Kinder- und Jugendheikunde Graz,
Allgemeine Pädiatrie, Graz, Austria, 2Universitätsklinik für
Kinder- und Jugendheilkunde Graz, Graz, Austria, 3National
Research Center for Maternal and Child Health, Neurology,
Astana, Kazakstan, 4Neuromuscular Reseach Department,
Medical University of Vienna, Wien, Austria
Introduction: Glucose-6-phosphate dehydrogenase deficiency (G6PD) is a
common X-linked inherited disorder affecting persons of African, Asian,
Mediterranean, or Middle-Eastern descent. The erythrocytes of the patients
express an increased vulnerability to oxidative stress. The majority of
persons with reduced enzyme activity is asymptomatic, but some have
episodic severe hemolysis and others chronic anemia. There are only a few
P034
X-linked Adrenoleukodystrophy: Severe Head
Trauma Masked Diagnosis—A Case Report
Haber E.1, Brunner-Krainz M.1, Erwa W.2, GruberSedlmeyer U.1, Schwerin-Nagel A.1, Kortschak A.1, Pilhatsch
A.3, Achatz E.4, Paschke E.2
1
Department of Paediatrics and Adolescent Medicine,
Medical University of Graz, Graz, Austria, 2Institute for
Medical and Chemical Laboratory Diagnostics, Medical
University of Graz, Graz, Austria, 3Department of Radiology,
Medical University of Graz, Graz, Austria, 4Department of
Paediatrics and Adolescent Medicine, Hospital Klagenfurt,
Klagenfurt, Austria
Introduction: X-linked adrenoleukodystrophy (OMIM 300100) is caused by
the deficiency of a peroxisomal transmembrane protein responsible for the
transport of very long chain fatty acids (ABCD1 gene). The various phenotypes (cerebral adrenoleukodystrophy, adrenomyeloneuropathy, Morbus
Addison only, and women with X-ALD) do not correlate with the known
mutations of the ABCD1 gene.1 In case of cerebral involvement, white matter
lesions can be seen in the magnetic resonance imaging (MRI) of the brain and
are graded by the Loes Score, which plays a role in prognosis and therapy.2
Hematopoietic stem cell transplantation (HCT) can stop the demyelinating
process in brain, but it has to be performed at an early stage of the disease.3,4
Case Report: We discuss the case of a 5-year-old boy, who experienced
severe head trauma at an age of 3 years. Initial MRI of the brain showed
lesions, which were interpreted as axonal injuries. About 10 months
later walking disability, difficulty with speech, and episodes of disorientation occurred. Another MRI of the brain was done, which showed
progressive white matter lesions. X-ALD was suspected due to the
findings in MRI and family history, as the mother reported at that
time, that her father suffered from adrenomyeloneuropathy. Mutation
analysis confirmed the diagnosis. Because of the advanced stage of the
disease (Loes Score 15 and Performance intelligence quotient 75), HCT
was no option anymore.2,3,4 The clinical course showed rapid progression. Discussion: The initial lesions in the brain MRI were all explained
by the head trauma. A follow-up of the cerebral MRI was missed to be
done. Unfortunately, the boy was diagnosed, when the disease had
already progressed to an advanced stage, so HCT was no option anymore.
References
1 Engelen M, Kemp S, de Visser M, et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis,
follow-up and management. Orphanet J Rare Dis 2012;7:51
2 Loes DJ, Fatemi A, Melhem ER, et al. Analysis of MRI patterns aids
prediction of progression in X-linked adrenoleukodystrophy. Neurology 2003;61(3):369-374
3 Miller WP, Rothman SM, Nascene D, et al. Outcomes after allogeneic
hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood
2011;118(7):1971-1978
4 Peters C, Charnas LR, Tan Y, et al. Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999. Blood 2004;104(3):881-888
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
An Unbalanced Translocation t(5;20) with
Duplication of 20q13.2q13.33 and Deletion of
5p15.33p15.2 Causes Cri Du Chat Syndrome
with Occipital Meningocele and Other Brain and
Organ Malformation
reports of rhabdomyolysis during a hemolytic crisis and one case report of
malignant hyperthermia during anesthesia. Case Report: A 17-year-old
patient of Middle Eastern origin came to our hospital because of
abdominal pain after sports and the ingestion of beans. He had normal
hemoglobin and red cell blood count, but moderate thrombopenia,
hyperbilirubinemia, and a creatine kinase (CK) of 6,939 U/L. During the
next days, the CK went up to 21,753 U/L with extensive high myoglobin
of more than 3,000 ng/mL. Lowest erythrocyte count was 4.47 T/L and
lowest hemoglobin 13.9 g/dL. Muscle biopsy revealed augmented
storage of glycogen. The whole-exome analysis by next generation
sequencing (NGS) showed a hemizygous pathogen mutation in the
exome 6 (c.563C>T; p.Ser188Phe) of the G6PD gene. Conclusion: In a
patient with rhabdomyolysis even without substantial hemolysis, a
G6PD should be considered. This diagnosis is essential advising the
patient concerning medicine and substance use.
S34
Abstracts
Munich, 17th to 19th September 2014
P035
Acute Disseminated Encephalomyelitis in a 12Month-Old Boy: A Case Report
Haber E.1, Brunner-Krainz M.1, Gruber-Sedlmayr U.1,
Kortschak A.1, Schwerin-Nagel A.1, Stefan R.1, Sorantin E.2,
Zobel G.1
1
Department of Paediatrics and Adolescent Medicine,
Medical University of Graz, Graz, Austria, 2Department of
Radiology, Medical University of Graz, Graz, Austria
Munich, 17th to 19th September 2014
Introduction: Acute disseminated encephalomyelitis (ADEM) is a rare
immune-mediated demyelinating disease of the central nervous system, often following an infection or in some cases a vaccination. Children
between 5and 8 years of age are mainly affected. The incidence for ADEM
is 0.64/100,000/year in children younger than 15 years and 0.8/100,000/
year in children aged 5 to 9 years.1 Presenting symptoms are encephalopathy and multifocal neurological deficits. The clinical course is
usually monophasic but recurring or multiphasic variants make the
differentiation to multiple sclerosis difficult.2 Case Report: We present a
1-year-old boy who was admitted to our hospital with cranial nerve
palsy 6th and disability to stand, sit, or walk 1 week after the onset of a
viral gastroenteritis. Cerebral magnetic resonance imaging (MRI)
showed asymmetric white matter lesions as well as lesions in brain
stem and basal ganglia. No infectious agent in cerebrospinal fluid, blood,
and stool was detected. Clinical symptoms resolved quickly within 5
days before therapy with high-dose corticosteroids was initiated. Clinical follow-ups showed normal development. Cerebral MRI 3 months
later showed regression of the initial lesions but still multiple white
matter lesions. The next MRI is planned. Conclusion: ADEM is a disease
of childhood normally with very good prognosis but sometimes not easy
to differentiate from multiple sclerosis. We find our patient with 1 year
of age notable compared with the mean age of 5 to 8 years at presentation of ADEM. Clinical and radiological follow-ups will be crucial to rule
out a multiphasic course or even chronic disease.
References
1 Pavone P, Pettoello-Mantovano M, Le Pira A, et al. Acute disseminated
encephalomyelitis: a long-term prospective study and meta-analysis. Neuropediatrics 2010;41(6):246-255
2 Alper G. Acute disseminated encephalomyelitis. J Child Neurol
2012;27(11):1408-1425
P036
Quality of Life and Physical Fitness in Children
and Adolescents with Epilepsy (EpiFit)
Hagn C.1, Walch R.1, Baumann M.1, Haberlandt E.1,
Frühwirth M.2, Rostásy K.1, Rauchenzauner M.2
1
Medizinische Universität Innsbruck, Department für
Kinder- und Jugendheilkunde I, Neuropädiatrie, Innsbruck,
Austria, 2Krankenhaus St. Vinzenz Zams, Abteilung für
Kinder- und Jugendheilkunde, Zams, Austria
Objective: The aim of this study (pilot study, EpiFit) was to demonstrate
the correlation between physical fitness and quality of life in children
with epilepsy. Methods: A total of 120 children aged between 6 and 18
years conducted a 6-minute walk test (6MWT) and had to complete a
standardized questionnaire (KINDL-R) to evaluate their personal level of
fitness. Children were divided into the following two groups: (1) the
patient group was composed of 60 children and adolescents with
idiopathic generalized or idiopathic focal epilepsy and (2) the control
group consisted of 60 healthy children. Two different versions of the
questionnaire were completed. One version was answered by the
children and a proxy version by their parents. Results: The analyses
revealed that the average health-related quality of life of children with
focal epilepsy was rated greater when compared with healthy children
(p ¼ 0.046). The parent-assessed quality of life of children with focal
epilepsy showed higher ratings than the evaluation of the proxy
versions of children with generalized epilepsy (p ¼ 0.022). In addition,
the personal valuations of the children with epilepsy concerning their
quality of life were better rated than the parent-assessed quality of life,
although not reaching statistical significance (p ¼ 0.340). In children
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
with epilepsy, a significant correlation could be shown between walking
distance and mental well being (r ¼ 0.406, p < 0.05). Fitter patients, who
were walking a longer distance, showed a higher grade of mental well
being. In contrast, no association could be demonstrated in the control
group of the healthy children (r ¼ #0.061, p > 0.05). Furthermore, the
study indicates a negative correlation between the quality of life and the
amount of time spent for TV and PC in children with epilepsy (r ¼
#0.334, p < 0.05) and healthy children (r ¼ #0.374, p < 0.05).
Conclusion: The results of the study show that quality of life in children
with focal epilepsy is greater when compared with healthy controls. Of
importance, quality of life in children with epilepsy might increase with
a reduction of consumption of computer/TV time in combination with
more physical activity. Educational programs are necessary to raise
awareness and deepen the knowledge about epilepsy among patients
and parents for a better understanding of and dealing with the disease
(e.g., FAMOSES).
P037
Epilepsy Surgery in Pediatric Long-Term
Epilepsy-Associated Tumors
Hartlieb T.1, Pieper T.1, Holthausen H.1, Winkler P.1, Blümcke
I.2, Kudernatsch M.3, Staudt M.1
1
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurologische Rehabilitation, Epilepsiezentrum für Kinder
und Jugendliche Vogtareuth, Germany,
2
Universitätklinikum Erlangen, Institut für
Neuropathologie, Erlangen, Germany, 3Schön Klinik
Vogtareuth, Klinik für Neurochirurgie und
Epilepsiechirurgie, Vogtareuth, Germany
Objective: Epilepsy surgery is a treatment option for children with
intractable focal epilepsy in benign long-term epilepsy-associated tumors
(LEAT). Pure tumor-lesionectomy is associated with poorer postoperative
seizure outcome in comparison with extended resections based on multimodal presurgical evaluation (Engel class1, 65-77% vs. 82–95%).1 Here, we
report our outcome data on epilepsy surgery in children with LEATs.
Methods: Retrospective analysis of 62 LEAT patients with a minimum
follow-up of 6 months of 430 patients who received epilepsy surgery
between September 1998 and December 2013 at our center. Tumor
location was mostly temporal (33/62). All patients underwent surface
video-electroencephalography monitoring and high-resolution magnetic resonance imaging. Additional invasive recordings were performed in 8 of 62 patients (all with subdural grids, five with
additional depth electrodes) for delineation of epileptogenic area and
mapping of eloquent cortex (Wernicke area [4/8], sensorimotor function
[2/8], Broca area [1/8]). Of the 62 patients, 57 received their first
operation here, while five patients had already received lesionectomies
at other centers and were referred for reoperation due to insufficient
seizure control. Results: Epilepsy outcome (Engel classification): class I
52 of 62, class II 8 of 62, class III 1 of 62, and class IV 1of 62. Conclusion:
Excellent postoperative seizures outcome (Engel class 1) could be
achieved in 52 of 62 patients (81%). This finding is compatible with
reports in the literature of a high success rate (Engel 1) of epilepsy
surgery in LEATs (82-95%), which is higher than the rate after pure
lesionectomies (65-77%). Therefore, besides complete tumor resection,
postoperative seizure freedom should be aimed at in children with
intractable focal epilepsy in LEATs. Invasive recordings (8/62) should be
detained for tumors in close relationship to eloquent cortical areas.
Combination of subdural grids and depth electrodes (5/8) enhances
diagnostic and therapeutic accuracy, recording ictal, and interictal data
from basal and mesial brain structures (i.e., hippocampus and insula)
and/or epileptogenic lesions and can furthermore serve as strategic key
structures for resection.
Reference
1 de Groot M, Reijneveld JC, Aronica E, Heimans JJ. Epilepsy in patients
with a brain tumour: focal epilepsy requires focused treatment.
Brain 2012;135(4):1002–1016
Abstracts
S35
Munich, 17th to 19th September 2014
A New Form of a Mitochondriopathy
P038
Hartmann B.1, Hu H.2, Kraemer N.1, Musante L.2, Fischer B.3,
Ropers H.2, Wienker T.2, Hubner C.1, Kaindl A.1
1
Klinik für Pädiatrie m.S. Neurologie, Charité ‐
Universitätsmedizin, Berlin, Germany, 2Max-PlanckInstitut für molekulare Genetik, Berlin, Germany, 3Institut
für Medizinische Genetik und Humangenetik; Charité,
Berlin, Germany
P039
Salmonella Meningitis after Reptile Exposure
by a 9-Week-Old Infant
Hofmann R.1, Rabsch W.2, Fruth A.2, Neubauer B.1, Hahn A.1
1
Zentrum für Kinderheilkunde und Jugendmedizin Gießen,
Abteilung für Neuropädiatrie, Gießen, Germany, 2Robert
Koch-Institut, Nationales Referenzzentrum (NRZ) für
Salmonellen und andere bakterielle Enteritiserreger,
Werningerode, Germany
Background: Salmonella is a common bacterial cause of gastrointestinal
infections and is mainly transmitted by contaminated food. A rarer but
significant model of transmission is a Salmonella infection after exposure to exotic reptiles. Here, we report the case of an infant with severe
Salmonella sepsis and meningitis, where the source of infection was a
bearded dragon living in the family’s household. Patient: Salmonella
enterica was found in the cerebrospinal fluid (CSF) and stool of a 9-weekold female infant with severe bacterial sepsis and meningitis (analysis of
CSF revealed a white blood cell count of 5,568 cells/µL, protein concentration of 3,784 mg/L, glucose level of 1 mg/dL, and lactate of 10.5 mmol/
L). Subtyping by the National Reference Centre for Salmonellae and other
Bacterial Enteric Pathogens of the Robert Koch Institute (RKI) identified
Salmonella enterica serovar Waycross and serovar Tennessee, which are
mainly found in reptiles. The source of the Salmonella infection was a
bearded dragon living as a pet in the family’s home, in which feces the
same Salmonella subtypes were identified. The infant received an
intravenous treatment with antibiotics for 10 days, during which her
health status improved rapidly. Although Salmonella was still found in
her stool, she was discharged from the hospital after consultation with
the local health authorities. Only 1 day later, the child was readmitted to
the hospital with severe sepsis and both Salmonella subtypes were again
identified in her CSF and stool. As there was no abscess formation, the
P040
Progressive Myoclonus Epilepsy Starting in
Early Childhood with a Mutation in the KCTD7
Gene
Hofmann-Peters A.1, Herting A.1, Biskup S.2, Polster T.1
1
Epilepsie-Zentrum Bethel/Krankenhaus Mara,
Kinderepileptologie Kidron, Bielefeld, Germany, 2CeGaT
GmbH, Tübingen, Germany
Caring for children with a progressive loss of acquired skills is one of the
most difficult situations, even more, if the etiology of the disease is
unknown. We report the characterization of a probably causal mutation
in KCTD7 in a 9-year-old boy with progressive myoclonus epilepsy
(PME) from the age of 2 years. Case Report: This boy’s early development was only slightly delayed when neck myoclonus and drop attacks
began at the age of 17 months. His electroencephalography (EEG) was
normal and a diagnosis of myoclonic-astatic epilepsy was made. Later
on, generalized tonic-clonic seizures appeared as well as series of
myoclonus in the upper body. At the age of 4 years, myoclonus was
continuously present in his hands. Loss of acquired skills with impaired
speech and gait started at the age of 3 years; at the age of 6 years, he was
no longer able to walk or to grasp. A reddish, papular rash was first noted
in his face, scrotum, and thighs at the age of 3 years 9 months and was
replaced by hyperpigmented skin within a few months. He actually has
continuous myoclonus in both the hands, eyelids, and the neck. There is
no active speech, but interaction with eye contact. His EEG shows
generalized slowing with multifocal epileptiform discharges. Diagnostic
work-up for PME at the age of 5 years did not provide evidence of a
causal disease (including neurophysiology, neurometabolic testing, CSF
analysis for antineuronal antibodies and neurotransmitters, and histopathology with electron microscopy of skin and muscle). Array comparative genomic hybridization revealed a duplication of 22q11.21 not
detected in the mother (father not available for testing), but there is no
evidence for a causal relationship. Gene panel sequencing disclosed a
probably homozygous mutation in the KCTD7 gene coding for a potassium channel. Disease course in families with mutations in KCTD7 was
congruent in many aspects to our patient. Discussion: Mutations in
KCTD7 have been shown to cause PME starting in early childhood.
Clinical differentiation between early onset PME and infantile epileptic
encephalopathy, even though not always possible, is helpful to reduce
the genetic analysis to a selected group of genes, making the whole
process more efficient.
P041
MuKieHS: Muscles of Children with Acquired
Cerebral Lesions
Jansen C.1, Wimmer C.1, Schröder A.2, Staudt M.1,
Berweck S.1
1
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurologische Rehabilitation, Epilepsiezentrum für Kinder
und Jugendliche, Tagesklinik, Vogtareuth, Germany,
2
Klinikum der Universität München Campus Innenstadt,
Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen
Kinderspital, München, Germany
Aim: A variety of clinical alterations in muscles and function can be seen
in children with acquired cerebral lesions. The aim of this prospective
study (which started March 2014) is to show structural alterations of
muscles using ultrasound and to investigate their correlation to parameters of function and activity. Methods: Only children who were
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Introduction: Mitochondriopathies are diseases caused by a defect in
energy metabolism and therefore manifest predominantly as multisystemic diseases. High-energy consuming organs such as muscle, heart,
and the central nervous system are therefore primarily affected leading
to symptoms such as muscle weakness, cardiomyopathy, and intellectual disability. The prevalence of mitochondriopathies is estimated to be
approximately 1:10,000. The majority of mitochondriopathies is caused
by mutations of nuclear-encoded genes rather than mitochondrialencoded genes. Here, we studied a consanguineous family with a new
form of a mitochondriopathy. Methods: The causative homozygous gene
mutation was identified by whole-exome sequencing and confirmed by
Sanger sequencing. Histochemical and biochemical methods as well as
electron microscopy and cell culture studies were performed using
patient material (primary fibroblasts and muscle biopsy specimen).
Results and Discussion: Using whole-exome sequencing, we detected
homozygous point mutations in a so far not disease-associated gene in
four children of a consanguineous family of Saudi Arabian descent with a
novel mitochondrial disease. Main features include intellectual disability, motor developmental delay with muscle weakness, epilepsy, deafness, optic nerve atrophy, ataxia, and a myelination disorder. The
mutated gene product is a nuclear-encoded, mitochondrially located
protein. It is important for the maintenance of mitochondrial integrity,
selective proteolysis, cell proliferation, and resistance against apoptosis.
The function of this protein in brain and muscle still remains unknown.
In the human fibroblasts of a patient, we detected a significant fragmentation of the mitochondrial network suggesting impaired mitochondrial dynamics as well as decreased proliferation rates. We are
currently studying further pathomechanisms underlying the disease,
also in light of putative interaction with other mitochondrial proteins.
We are seeking for patients with a similar phenotype.
source of the reinfection was most likely the remaining Salmonella in
her intestine. After a 6-week-period of intravenous antibiotic treatment,
both Salmonella subtypes were no longer found in CSF and stool of the
infant. The child did not suffer from a reinfection since then. Conclusion:
This is the first report of Salmonella meningitis after reptile exposure in
Germany. According to the RKI, reptile-associated salmonellosis in
children younger than the age of 2 years has tripled since 2006. A
further increase seems to be likely as reptiles are more frequently kept as
pets. Also, infants seem to be susceptible to disease transmission already
by small numbers of Salmonella. They should receive an antibiotic
therapy for several weeks.
S36
Abstracts
Munich, 17th to 19th September 2014
Munich, 17th to 19th September 2014
neurologically healthy before the incident are included. A first examination and ultrasound is performed not later than 3 months after the
incident and repeated every 4 weeks for the first 3 months, thereafter
every 8 weeks. Examination includes M. biceps brachialis (BB), M. rectus
femoris (RF), M. tibialis anterior (TA), M. gastrocnemius medialis (GM)
on both sides. Described are muscle structure (granular/gr, lamelliform/
la, and mixed/mi), its distribution pattern (homogeneous/ho and inhomogeneous/in), the thickness of the muscle and subcutaneous fat and
the echo intensity (0 to +++). Clinically examined are muscular strength
(1-5), passive range of motion (pROM), muscle tone (modified Tardieu
scale 0-4), and the Gross Motor Function Measure (GMFM). Results: As
an example, we show the results of a 4-year-old boy, 28 days after a
cerebral hemorrhage with a spastic right hemiparesis.
Table 1:
Ultra-
Muscle
Subcutaneous
Echo
Muscle struc-
sound
thickness
fat
intensity
ture
Distribution
Left
Right
Left
Right
Left
Right
Left
Right
Left
BB
12.7
12.8
2.3
2.1
0
0
mi
mi
ho
Right
ho
RF
13.2
11.8
5.1
5.0
0
0
gr
gr
ho
ho
TA
15.3
16.0
2.5
3.0
0
0
mi
mi
ho
ho
GM
13.7
9.6
2.8
2.7
0
+
gr
ge
ho
ho
Table 1:
Clinical examination
pROM
Muscle
strength
Left
Right
Left
Right
Left
Right
Elbow (flex/ext.)
150/0/0
150/0/0
5/5
1/1
0/0
1/2 (60°)
Hip (flex/ext)
120/0/0
120/0/0
5/5
3/1
n.d.
n.d.
+ knee-flex
10/0/30
10/0/30
DE: 5
DE: 1
0/0
0/3 (#10°)
+ knee-ext
5/0/30
#/5/30
m. Tardieu
ankle de/pf
Conclusion: Overall, 28 days after the lesion, an increased echo intensity
and a decreased thickness of the GM right could be seen in ultrasound.
Compatible with this, a decreased pROM in the right ankle and an
increased tone in the right plantarflexors were apparent. In the future,
more children will be included in the study. Relying on data from adult
stroke patients and children with cerebral palsy, muscle alterations in
ultrasound and a correlation between structural and functional changes
can be expected. The overall purpose is to optimize the therapy of
children with movement disorders in an early phase of rehabilitation,
especially regarding the focus and aims in physiotherapy and occupational therapy, the indication and point of tone-modifying procedures
and the supply with aids and appliances.
P042
Induction of Neuronal Plasticity by Transcranial
Biphasic Quadri-Pulse Stimulation with One or
Two Full-Sine Cycles
H. Jung N.1, Gleich B.2, Siebner H.R.3, Kalb A.1, Gattinger N.2,
Mall V.1
1
Department of Pediatrics, Technische Universität
München, Munich, Germany, 2 Zentralinstitut für
Medizintechnik at Technische Universität München
(IMETUM), Munich, Germany, 3 Danish Research Centre for
Magnetic Resonance (DRCMR), Copenhagen University
Hospital Hvidovre, Hvidovre, Denmark
Question: Neuronal plasticity in form of long-term potentiation (LTP) is
considered to be the underlying neurophysiological mechanism of
learning and memory and plays a pivotal role in development and
developmental disorders. Transcranial magnetic stimulation is a noninvasive and widespread method to induce and evaluate neuronal plasticity in humans. Biphasic transcranial quadri-pulse stimulation (QPS)
consisting of one full-sine cycle for each stimulus demonstrated to be
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
effective in induction of neuronal plasticity in human primary motor
cortex. Two full-sine cycles demonstrated to be effective in evaluation of
local excitability. Here, we aimed to study the effectiveness of QPS with
two full-sine cycles (quadro-burst stimulation, QBS) in comparison to
biphasic QPS with one full-sine cycle in induction of neuronal plasticity.
Methods: We investigated 10 healthy volunteers (females: n ¼ 6; males:
n ¼ 4; mean age, 24.7 years; range, 23-36 years) with QPS consisting of
one and two full-sine cycles (duration, 160 µs) separated by an interstimulus interval of four stimuli of 5 ms and an interburst interval of 200
ms with a total amount of 1,440 pulses (total duration approximately 2
minutes). Resting motor threshold (rMT), and motor evoked potential
(MEP) amplitudes with stimulus intensities to target amplitudes of 1 mv
(SI1mV) were measured before (Pre) intervention, directly after (Post 1),
after 15 minutes (Post 2), after 30 minutes (Post 3), and after 60 minutes
(Post 4). Results: We found a significant increase of MEPs after QPS with
one and two full-sine cycles at interstimulus intervals of 5 ms and
interburst intervals of 200 ms. While the MEP increase was immediately
present after QPS with two full-sine cycles lasting for 1 hour (Post 1-4),
QPS with one full-sine cycle resulted in a delayed MEP increase which
became significant after 15 minutes (Post 2). No significant changes in
rMT and no adverse events were observed. Conclusion: QPS with one
and two full-sine cycles of the human primary motor cortex demonstrated to induce a lasting increase in corticospinal excitability. Considerable differences in time course may be suggestive of different
underlying neurophysiological mechanisms. Varying the pulse configuration in very short protocols of QPS may provide new and safe
opportunities in investigations of neuronal plasticity in development
and developmental disorders.
P043
Rhabdomyoma in a 3-Year-old Girl As the Only
Clinical Manifestation in Tuberous Sclerosis
Complex: Significance of Molecular Genetics
Kaiser O.1, Neudorf U.2, Lutz S.1, Schara U.1
1
Paediatric Neurology, Developmental Neurology and
Social Paediatrics, University of Essen, 2Paediatric
Cardiology; University of Essen
Aim: Tuberous sclerosis complex (TSC) is a rare multisystemic disorder
with a great clinical variety of presentation in frequently occurring
multiple organ manifestations. According to the clinical diagnostic
algorithm, tuberous sclerosis is determined by the evidence of two
major criteria (including rhabdomyoma and hypomelanic macules) or a
major criterion and two minor criteria. As per the diagnostic criteria
revised in 2012, verification of mutations in TSC1 or TSC2 genes are
sufficient for a diagnosis. Almost all patients have abnormalities such as
hypomelanic macules, angiofibromas, periungual fibromas, and shagreen patches. The majority of patients have abnormalities in the central
nervous system, such as tubera and subependymal nodules, only in a
few patients giant cell astrocytoma occur. Less known is the isolated
occurrence of rhabdomyoma without any further organ manifestations.
Case Report: We present a 3-year-old girl with prenatally diagnosed
rhabdomyoma of the left ventricle and a positive family history of TSC.
Moreover, regularly follow-ups over 3 years have not shown any other
organ manifestations, particularly no skin abnormalities; electroencephalography, cranial magnetic resonance imaging, and abdominal
sonography showed normal findings. The cognitive development of the
young female patient has been at normal level so far. The cardiac
findings, as the only abnormality, was declining and always without
hemodynamic relevance. For the diagnosis of TSC by clinical features
alone, the rhabdomyoma was not sufficient, though. A mutation in the
TSC2 gene confirmed the suspected diagnosis of TSC. Conclusion:
Diagnosis of TSC is usually confirmed by clinical criteria with the
occurrence of major and minor criteria. The isolated occurrence of
rhabdomyoma without further organ manifestations is a rare phenomenon. In this case, the diagnosis could solely be confirmed via molecular
genetics. The case shows, besides the variance of TSC, the importance of
molecular genetics. Diagnosis of TSC in isolated rhabdomyoma can be
confirmed genetically with mutations in TSC1 and TSC2 genes in 75 to
90% of the cases.
Abstracts
S37
Munich, 17th to 19th September 2014
P044
Congenital Myasthenic Syndrome with Severe
Apnoes Requiring Intubation and
Arthrogryposis: Therapeutic Consequence of
Genetics
Congenital myasthenic syndromes (CMS) result from the failure to
achieve muscle depolarization due to disorders in the structure and
function of the neuromuscular synapse. Depending on the genetical
disorder they can be divided into presynaptic, synaptic, and postsynaptic defects. The therapy depends on the structural defect of the neuromuscular junction and the genetic defect. There is no strong genotypephenotype correlation, the clinical situation alone cannot determine the
required therapy. Therefore, we prefer a fast genetic testing during
hospital treatment. We describe a 7-month-old boy with a muscle
hypotonia, severe contractions, and recurrent apnoeic crises as requiring ventilator support. The repetitive nerve stimulation showed a
decrement of the muscle of 54% suspected for a CMS. Intravenous
application of pyridostigmin caused a strong impairment of the situation by producing lots of secretion, tears, and arterial hypotonia with no
improvement of the muscle strength. Suction of secretion, atropin
intravenous, and oxygen via nasal tube was necessary. After the tensilon
testing, we suspected a CMS due to a slow-channel syndrome or a
mutation of the COLQ gene. The genetic testing was necessary for further
investigations. The genetic testing showed a homozygote mutation of
the CHRNA1 gene: c.199A>T;p.Asn67Tyr, which is first described in our
patient. The CHRNA1 gene encodes for the α subunit of the acetylcholine
receptor. Autosomal recessive mutations of the CHRNA1 gene are
described just in few patients. The phenotype probably ranges from
fetal akinesia to severe CMS. Severe apnoes and contractions in patients
with CMS were a clinical clue for mutations of the RAPSN or CHAT gene so
far. The genetic test ensures the diagnosis of a CMS, a slow channel
syndrome or a mutation of the COLQ gene could be excluded. The
therapy with pyridostimin could be continued. Therefore, we recommend a much faster genetic testing during the patient’s stay in hospital
to be able to decide which therapy the patient need.
P045
Intima-Type Vasculopathy in Neurofibromatosis
Type 1
Keppler J.1, Fiedler A.2
1
Klinikum St. Marien Amberg, Klinik für Kinder und
Jugendliche, Amberg, Germany, 2Klinikum St. Marien, Klinik
für Kinder und Jugendliche, Amberg, Germany
Introduction: Neurofibromatosis type 1 is an autosomal-recessive,
monogenetic disease (NF1 gene 17q22.1) with an incidence of
1:3,000. Clinical symptoms affect skin, eyes, central and peripheral
nervous system, and bones. We report about a 10-year-old girl with
intima-type vasculopathy followed by peripheral arterial occlusive
disease grade 4 according to the neurofibromatosis. Case Report: At
the age of 6 years, a difference in the length of legs was noticed and
treated with insoles and orthopedic shoes. At the age of 9 years,
consultation of an orthopedic specialist revealed genu varum and
temporarily epiphysiodesis was done. After 8 months of a therapy
refractory, painful soft tissue infection on one foot occurred. Despite
local and systemic antimicrobial therapies a dry ulcer on the forefoot
and humid necroses between the toes developed. Further diagnostic
measures showed demineralization of the lower leg and tarsus as well as
old fractures of the metatarsalia. Conventional angiography and angiomagnetic resonance imaging revealed an obliteration of the posterior
tibial artery and high-grade stenoses of the anterior tibial artery and the
fibular artery with multiple collaterals. In synopsis of the clinical and
radiographic findings, a peripheral arterial occlusive disease grade 4
was diagnosed. After ineffective medicamentous and interventional
P046
Horizontal Gaze Palsy and Rapidly Progressive
Scoliosis: Typical Findings in ROBO3 Mutations
Koch J.1, Landauer F.2, Keindl T.3, Sloman M.4
1
Universitätsklinik für Kinderheilkunde und
Jugendmedizin, Salzburg, Austria, 2Universitätsklinik für
Orthopädie, Salzburg, Austria, 3Universitätsklinik für
Augenheilkunde und Optometrie, Salzburg, Austria,
4
Molecular Genetics Department, Royal Devon and Exeter
Hospital, Exeter, United Kingdom
Background: Horizontal gaze palsy with progressive scoliosis (HGPPS) is
a rare autosomal recessive disorder characterized by the absence of
conjugate horizontal eye movements and early onset rapidly progressive
scoliosis. The disorder is caused by mutations in the ROBO3 gene, which
has an important role in axonal guidance and neuronal migration during
embryonic development of brain stem and rhombencephalon. Cerebral
magnetic resonance imaging (MRI) shows a typical pattern with butterfly configuration of the medulla, a deep midline pontine cleft, and
pontine hypoplasia. Diffusion tensor imaging maps can show the
absence of decussating pontocerebellar fibers and superior cerebellar
peduncles. Motor development is delayed in many patients whereas
cognitive function does not seem to be grossly impaired. Case Report:
The girl was born at term as the first child of nonconsanguineous
Austrian parents. Birth weight was normal, postnatal adaptation was
uncomplicated. At the age 4 months, she was presented to orthopedics
because of abnormal head posture, at age 6 months to ophthalmology
due to strabismus. When she was 8 months old, horizontal gaze palsy
was diagnosed and incomplete Moebius syndrome was suggested. The
girl was supported by orthoptist therapy and received physiotherapy for
abnormal head posture. She was first presented to our neuropediatric
department at the age of 1 year at which point she did not show scoliosis
and motor and cognitive development were normal. We recommended
an MRI scan at 18 months and the continuation of supportive therapy.
Over the following months, our patient developed a rapidly progressive
scoliosis and the MRI showed a deep midline cleft of pons and brain
stem. Clinical symptoms and MRI findings were highly suggestive of a
ROBO3 mutation. Therefore, we initiated molecular genetic testing and
could confirm a homozygous frameshift mutation (c.2576del) in ROBO3.
Conclusion: Clinical findings of horizontal gaze palsy in an infant or
child together with scoliosis are highly suggestive of a mutation in
ROBO3. MRI findings are very characteristic. Early diagnosis is important
with respect to genetic counseling of HGPPS families. A main focus of
treatment is physiotherapy to control progressive scoliosis. Threedimensional correction using thermoplastic braces and corrective spine
surgery may be necessary.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Kauffmann B.1, Bunten S.2, Schara U.3, Abicht A.4
1
Klinik für Kinder- und Jugendmedizin, Klinikum Links der
Weser, Bremen, Germany, 2Institut für klinische
Neurophysiologie, Klinikum Bremen Ost, Bremen, Germany,
3
Universitätsklinikum Essen, Kinderklinik1, Bereich
Neuropädiatrie, Entwicklungsneurologie und
Sozialpädiatrie, Essen, Germany, 4Medizinisch Genetisches
Zentrum, München, Germany
attempts to improve perfusion, amputation of the lower leg was
performed. Histological examination of the arterial blood vessels in
the amputation stump provided evidence of changes in terms of an
intima-type vasculopathy with subtotal to total stenoses due to intimal
hyperplasia consistent with vascular neurofibromatosis. Conclusion:
Vascular complications in neurofibromatosis type 1 are described in
literature as fibromuscular dysplasia in renal arteries and as stenoses or
ectasias of the carotids or the cerebral arteries. Vasculopathies of the
peripheral arteries leading to the clinical picture of a peripheral arterial
occlusive disease are extremely rare, especially in childhood. Differences
in length or circumference of extremities, trophic dysfunction, abnormal wound healing, or persistent pain should result in further angiologic diagnostics.
S38
Abstracts
Munich, 17th to 19th September 2014
P047
Intestinal Atony As a Late Symptom of Infantile
Spinal Muscular Atrophy
Munich, 17th to 19th September 2014
Köhler C.1, Schmidt-Choudhury A.2, Rothoeft T.3, Thiels C.1,
Lücke T.1
1
Klinik für Kinder- und Jugendmedizin der RuhrUniversität Bochum, Neuropädiatrie mit Sozialpädiatrie,
Bochum, Germany, 2Klinik für Kinder-und Jugendmedizin
der Ruhr-Universität Bochum, Abteilung für pädiatrische
Gastroenterologie, Bochum, Germany, 3Klinik für Kinderund Jugendmedizin der Ruhr-Universität Bochum, Bochum,
Germany
Intestinal atony as a late symptom of infantile spinal muscular atrophy
(SMA). Patients affected with the severe infantile form of SMA die mostly
in their early childhood due to respiratory insufficiency and bulbar
paralysis. A homozygous deletion in the “Survival Motor Neuron” 1 gene
(SMN1 gene) leads to deficiency of SMN protein and degeneration of the
spinal motor neuron. But SMA is not only a motor neuron disease, other
organs can be involved as clinical reports indicate. Reasons as secondary
neuronal damage/muscle atrophy or the primary lack of SMN are
discussed in literature.1 We report the case of a 14-year-old girl with
SMA due to homozygous deletion in the SMN1 gene. Complications of
respiratory insufficiency in early childhood led to severe brain damage.
With tracheotomy and continuous invasive ventilation medical state
was stable over years. But over the past 2 years, severe constipation and
instable vegetative functions (temperature, blood pressure, and stability
of pulse) augmented. These problems were at first interpreted as central
dysregulation phenomena due to severe brain damage. But when
investigations for acute ileus were performed, the complete atony of
the gastrointestinal system without any ultrasonographic order radiological sign of “acute” paralytical ileus i.e. distended intestinal loops was
unexpected. The ultrasonic exploration showed completely amotile
narrow intestinal loops comparable to the localized findings in M.
Hirschsprung in the small and large bowels. About 8 hours after
application of contrast agent via polyethylene glycol, no transport of
contrast agent was documented. Complete paralytical ileus can be
interpreted as late sequel of SMA. Presumable the other signs of
autonomic dysregulation can also be interpreted as late symptoms of
severe SMA. In gaining longer lifetime for patients with severe SMA
through intensive medical care measures, peripheral organ deficiency
and vegetative dysregulation come to the fore.
Reference
1 Shababi M, Lorson CL, Rudnik-Schöneborn SS. Spinal muscular
atrophy: a motor neuron disorder or a multi-organ disease? J Anat
2014;224(1):15–28
P048
One Patient with Sturge-Weber Syndrome and
Stroke-Like Episodes: Our Experience with
Acetylsalicylic Acid
Kovacevic-Preradovic T.1
1
Epilepsiezentrum Radeberg-Kleinwachau,
Neuropädiatrie, Radeberg, Germany
Introduction: The association of cerebral leptomeningeal angioma and
ipsilateral facial nevus flammeus in the territory of the first branch of the
trigeminal nerve is known as the sporadic neurocutaneous disease
Sturge-Weber syndrome (SWS). The cases with the absence of a facial
angioma are usually considered to be variants of this syndrome. Among
other frequent symptoms such as seizures, headaches, developmental
delay, and glaucoma, stroke-like episodes are only sporadically reported
associated features. There is no evidence-based therapeutic recommendation for this condition. A few case reports suggest that prophylactic
treatment with low-dose acetylsalicylic acid (ASS) may prevent the
neurological decline. Case Report: This almost 11-year-old girl had
uneventful early development. She was diagnosed in her 2nd year, after
she had her first seizures consisting of right hemiconvulsions. No facial
nevus was present at birth. The magnetic resonance imaging demonstrated unilateral brain involvement showing atrophy and calcifications
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
in the left temporo-parieto occipital region, compatible with SWS. The
neurological examination revealed no neurological signs. After the
administration of valproate, the cessation of seizures was achieved. At
the age of 8 years, she developed paroxysmal events with a different
semiology. A few times per year she vomited, had moderate headache,
and a stiff neck. A sudden onset of mild numbness of the right leg and
disturbance in the visual field accompanied these episodes. No other
symptoms occurred. We saw one habitual episode soon after the
admittance in our center. All symptoms resolved during the following
24 hours. The electroencephalography performed during and after this
attack showed no epileptic activity but regional slowing with complete
resolution. The etiology of attack was presumed to be ischemic, socalled stoke-like episode and a prophylaxis with ASS (2 mg/kg/d) was
initiated. Thereafter, the paroxysmal events stopped and have not
recidivated in the past 18 months of follow-up. Conclusion: Early
recognition and energetic therapy of symptoms remains a cornerstone
in the management of SWS. ASS is potentially safe and effective
prophylaxis of neurological deterioration in individuals with SWS,
although its use in the pediatric population remains controversial
disputed. In the absence of guidelines and randomized controlled trials,
individual case reports increase the knowledge and clinical competence
in confronting these patients.
P049
Prolonged and Devastating Clinical Course in
Atypical Neuromyelitis Optica
Kraus V.1, Leiz S.2, Mall V.3, Burdach S.4, Makowski C.1
1
Kinderklinik München-Schwabing, Technische Universität
München, Neuropädiatrie, München, Germany, 2Klinikum
Dritter Orden, Klinik für Kinder- und Jugendmedizin,
München, Germany, 3kbo-Kinderzentrum München,
Lehrstuhl für Sozialpädiatrie TUM, München, Germany,
4
Kinderklinik München-Schwabing, Technische Universität
München, Pädiatrie, München, Germany
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease
affecting the optic nerve and the spinal cord. Antibodies (Ab) to
Aquaporin-4 (AQP-4) and sometimes to myelin oligodendrocyte glycoprotein (MOG) are characteristic serological findings. We present the
case of a 9-year-old boy with seronegative atypical NMO showing
recurrent episodes of isolated longitudinal extensive transverse myelitis
(LETM). He presented in December 2010 with paresis of his left leg
following flu vaccination. LETM with areas of beginning necrosis was
diagnosed. Blood-brain barrier disruption, oligoclonal band and highly
elevated interleukin 6 were found in cerebrospinal fluid. Clinically, the
entire spinal cord was affected with tetraparesis and inverted breathing.
He was treated with steroids, plasmapheresis, cyclophosphamide
(CPM), and immunoglobulins. Paraplegia starting from Th9 and a
neurogenic bladder disorder persisted. AQP4- and MOG-Ab were repeatedly tested negative. There was no evidence of optic neuritis during
the follow-up period. In July 2013, he experienced a first relapse with
weakness of the upper extremities following oral herpes infection. CSF,
blood, and magnetic resonance images showed identical findings to the
first episode. After steroids, plasmapheresis and CPM he showed no
clinical improvement and lost his hand function. After 27 days, application of CPM again following oral herpes infection he experienced a
second relapse with tetraparesis, sensibility loss starting at Th2, dry
mouth, and neck pain. Lumbar puncture was no longer possible. He
showed no improvement to steroids and plasmapheresis, but the
inflammation progressed to the midbrain. Finally, respiratory failure,
seizures, and cardiac arrest September 2013. In conclusion, we suspect
NMO-spectrum disorder (high-risk NMO), possibly triggered by infection or vaccination without NMO- and MOG-Ab nor optic nerve
involvement. The clinical picture is characterized by a polyphasic course
with late relapses and poor prognosis. Our case demonstrates an
unusual clinical course of LETM and should open discussion about the
variable clinical picture of NMO in childhood.
Abstracts
S39
Munich, 17th to 19th September 2014
P050
Sinus Vein Thrombosis in Nephrotic Syndrome
As a Complication of Steroid Therapy
Kraus V.1, Strotmann P.2, Dressel P.3, Burdach S.3, Makowski
C.1
1
Kinderklinik München-Schwabing, Technische Universität
München, Neuropädiatrie, München, Germany, 2KfHNierenzentrum für Kinder und Jugendliche beim
Städtischen Klnikum München-Schwabing, München,
Germany, 3Kinderklinik München-Schwabing, Technische
Universität München, Pädiatrie, München, Germany
P051
Implementation of a Guideline for the Diagnosis
of Fetal Alcohol Syndrome
Landgraf M.1, Heinen F.1
1
Dr. von Haunersches Kinderspital, Universität München,
Pädiatrische Neurologie, Entwicklungsneurologie und
Sozialpädiatrie, München, Germany
Background: Up to 30% of all pregnant women drink alcohol. The
intrauterine alcohol exposure can lead to fetal alcohol syndrome
(FAS). FAS has an estimated prevalence of 8 per 1,000 births. Until
now, many professional groups are not informed sufficiently about this
syndrome and only a fraction of the affected children are diagnosed
early in the lifetime. The toxically determined impairments of functions
and everyday life can be influenced positively by early and individual
support of the patients. Methods: FAS can be diagnosed by means of the
German S3 guideline. This guideline is based on evidence-assessed
literature and was developed together with the relevant professional
societies, the patient support group FASD Germany and other FAS
experts. For implementation of the guideline content, different paths
were trodden to inform as many professional groups as possible about
FAS. Results: The guideline can be downloaded for free from http://
www.awmf.org/leitlinien/detail/ll/022-025.html. For a quick practical
orientation, the guideline recommendations were summarized in an
algorithm and a pocket guide was developed. For each diagnostic
column (growth deficiencies, facial anomalies, and abnormalities of
the central nervous system), differential diagnosis of FAS were integrated in the pocket guide. In addition, possible risk factors for maternal
alcohol use and for the development of FAS are described. A guideline
book FAS (Series Pediatric Neurology, Kohlhammer Verlag, Stuttgart,
Germany) was composed and distributed in a high quantity free of
charge to the participating professional societies for further dissemination, to the patient support group, to the FAS experts, to all practicing
neuropediatricians, to all centers for pediatric and developmental
P052
Fronto-Insular Epilepsy in Children: Semiology,
Diagnostic Approaches, and Surgical Strategies
Lange J.1, Pieper T.1, Kudernatsch M.2, Holthausen H.1,
Winkler P.1, Coras R.3, Staudt M.14
1
Department of Neuropaediatrics, Neurologic
Rehabilitation, Epilepsy Center for Children and
Adolescents, Schön Klinik Vogtareuth, Vogtareuth,
Germany, 2Clinic for Neurosurgery and Epilepsy Surgery,
Schön Klinik Vogtareuth, Vogtareuth, Germany,
3
Department of Neuropathology, University Hospital,
Erlangen, Germany, 4Department Pediatric Neurology and
Developmental Medicine, University Children’s Hospital,
Tübingen, Germany
Objective: Patients suffering from intractable focal epilepsy due to
lesions in the fronto-insular region present a semiology consisting of
frontal, temporal, and insular symptoms. The polymorphic semiology
reflects the seizure spread and different symptogenic zones, easily
explained by the close anatomical and network connections to the
orbitofrontal region, the mesial temporal and insular structures. When
these patients are referred for surgery due to drug resistance, a complete
removal of the lesion and the ictal onset zone is frequently difficult
(branches of the middle cerebral artery, proximity to speech areas, or
corticospinal tract). Here, we report seizure semiology, diagnostic workup, surgical strategies, and seizure outcome in nine children and
adolescents (three girls) with fronto-insular epilepsies (FIE), eight of
which underwent surgery. Methods: High-resolution magnetic resonance imaging (MRI) and fMRI Fiber tracking in all. Age at surgery was
10.5 years (range, 3.6-21.7 years). Invasive presurgical diagnostics in five
patients (three stereo-electroencephalography (EEG) and two subdural
grids/depth electrodes). Electrocorticography was performed in two
patients. Postop follow-up ranged from 6 to 32 months (mean, 15.4
months). Results: Auras: Vegetative (n ¼ 3), somatosensory (n ¼ 3),
epigastric (n ¼ 3), and nonspecific (n ¼ 3). Seizures: Focal-clonic (n ¼ 2),
vegetative (n ¼ 1), versive (n ¼ 1), secondary generalized tonic-clonic (n
¼ 2), tonic (n ¼ 6), absences (n ¼ 2), not classified (n ¼ 1), psychomotor
(n ¼ 1), and hypermotor (n ¼ 1). Overall, two patients had suffered from
infantile spasm. Language lateralization: two ipsilesional (by fMRI and
by seizure semiology), three contralesional (by fMRI and functional
transcranial doppler sonography), and four undefined. Preserved ictal
speech was observed in five patients. Etiology: Focal cortical dysplasia II
in six and two patients were observed with mild malformations of
cortical development. Age at onset of epilepsy was 2.3 years (range, 0.17 years). Seizure outcome: Seizure free (Engel 1a): n ¼ 5, seizure
reduction (Engel 1d): n ¼ 1, no improvement (Engel 4a): n ¼ 1, and
follow-up < 6 months: n ¼ 1. None of the patients experienced
permanent deficits in motor or language function after the operation.
Conclusion: Children suffering from FIE may be candidates for surgical
treatment, even if the risks for postoperative language and motor
deficits are considerable. Neither MRI, nor seizure semiology, nor
surface EEG allow a precise delineation of the epileptogenic zone, which
makes invasive recordings and diagnostic techniques necessary. This is
accompanied by more favorable results in terms of postoperative seizure
outcome and lowering the risk of permanent neurological complication.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
We present the case of a 2-year-old boy with nephrotic syndrome. At the
time of his presentation, he was in remission and on reduced steroid
therapy (2.5 mg/kg). Clinically, he showed a left focal secondary generalized seizure. On brain, magnetic resonance imaging (MRI) thrombosis
of the superior sagittal and the transverse sinus was detected. Electroencephalography (EEG) showed isolated electrical status epilepticus of
the right hemisphere. Protein excretion in urine was elevated (150.5 mg/
L), albumin (2.1 g/dL) and protein (5 g/dL) levels as well as protein S (25%)
in blood was low. ATIII was normal. Low-molecular-weight heparin was
titrated to reach a therapeutic level after 12 hours and was then changed
to unfractionated heparin. Midazolam and phenobarbital stopped electrical status epilepticus and antiepileptic treatment was then changed
to levetiracetam. Genetic testing for hereditary thrombophilia revealed
homozygous Methylenetetrahydrofolate reductase and factor V point
mutation. Follow-up MRI 10 days later showed partial increase of the
thrombosis with formation of collaterals. EEG improved. Neurologically,
the patient was symptom free. Cyclosporin A was added because of
steroid resistance. Seven days later prerenal failure was noted. Biopsy
showed minimal change glomerulonephritis. Remission was again
achieved by protein- and fluid substitution and steroid therapy. After
6 weeks, he showed almost complete resolution of the thrombosis. Sinus
vein thrombosis as complication of nephrotic syndrome is typically
characterized by loss of protein and ATIII early in the disease course. In
our case, ATIII was normal, so sinus vein thrombosis is rather a
complication of steroid therapy on the basis of hereditary
thrombophilia.
neurology and to all youth welfare offices in Germany. The guideline
was discussed at international congresses and was published internationally. Conclusion: With the previous steps of implementation, many
relevant professional helpers of the health and social system could be
reached and informed about FAS. The resonance of the professionals and
patients was highly positive. A German App for the diagnosis of FAS will
be finalized in short time. Many further steps are necessary to intensify
the education about FAS and therefore to provide a basis for concrete
support for affected persons.
S40
Abstracts
Munich, 17th to 19th September 2014
P053
Migraine with Visual Aura: A Clinical
Manifestation of Cerebrovascular Disorders in
Childhood
Munich, 17th to 19th September 2014
Langhagen T.1, Borggräfe I.2, Fesl G.3, Landgraf M.2, Heinen
F.2, Gerstl L.2
1
Klinikum der Universität München, Deutsches Schwindelund Gleichgewichtszentrum, München, Germany, 2Dr. von
Haunersches Kinderspital, Ludwig-MaximiliansUniversität München, Abteilung für Pädiatrische
Neurologie, Entwicklungsneurologie und Sozialpädiatrie,
iSPZ, München, Germany, 3Klinikum der Universität
München, Abteilung für Neuroradiologie, München,
Germany
Cerebral vascular pathology mostly gets manifest in early adulthood.
Bleeding, epileptic seizure, and focal neurologic deficits are the most
common clinical presentations leading to the diagnosis. We present two
children with migraine headache and visual aura as first symptoms. Case
1: A 7-year-old girl suffers from classical clinical symptoms of a migraine
with visual aura. Cranial magnetic resonance imaging (MRI) scan
revealed a large arteriovenous (AV) malformation in the right occipital
lobe without signs of bleeding. As there were no epileptic seizures and
just minimal restriction in the visual field, a watchful-waiting approach
was preferred. In the 7 year follow-up, the clinical manifestation
remained stable with variable amount of migraine attacks. Though
the follow-up MRI showed an unchanged overall size of the AV malformation, the venous drainage and shunt volume raised and thereby the
risk of bleeding. The possible and also risky therapeutic options versus
further watchful-waiting approach are actually discussed with the
family. Case 2: A 10-year-old boy suffers, since he is 7 years old, from
left-sided temporal-parietal headache with visual aura and vertigo. As
the frequency of the attacks significant rose (2-4 attacks/week), the boy
sought medical advice. Cranial MRI and the following angiography
showed a giant intracranial aneurysm of the cavernous part of the
internal carotid (two aneurysm “pockets” with 1.5 cm diameter each)
with local compression especially of the left optic nerve. Hints for an
aneurysm associated illness or familiar burden were not found. After a
positive occlusion test, a combined neuroradiological and neurosurgical
approach with coiling and clipping of the left internal carotid was
realized without complications. Conclusion: In children suffering
from migraine with visual aura, which presents less often than migraine
without aura, a cranial MRI should be considered, as it may be the first
clinical sign of rare cerebrovascular disorders.
P054
Acute Aphasia in Childhood and Adolescence:
Age Effects on Functional Recovery
Lidzba K.1, Küpper H.1, Kluger G.2, Staudt M.12
1
Universitätsklinik für Kinder- und Jugendmedizin
Tübingen, Neuropädiatrie, Entwicklungsneurologie,
Sozialpädiatrie, Tübingen, Germany, 2Schön Klinik
Vogtareuth, Klinik für Neuropädiatrie und Neurologische
Rehabilitation, Epilepsiezentrum für Kinder und
Jugendliche Vogtareuth, Germany
Background: A perinatal left hemispheric infarct can, in most cases, be
well compensated with respect to language. At this early developmental
stage, not only perilesional, but also contralesional reorganization of
language can support functionally successful compensation. Data on
infarcts acquired in childhood and adolescence is, however, less clear.
After language acquisition, left-hemispheric infarcts often cause aphasia, with variable recovery. Patients with persistent aphasic symptoms
document an obvious lack of a successful reorganization. The age at
infarct probably significantly influences the compensatory potential,
but literature on this matter is scarce. Method: In a cooperative project
of Schön Klinik Vogtareuth (Clinic for Pediatric Neurology and Neurological Rehabilitation) and the University Children’s Hospital Tübingen
(Pediatric neurology), we first identified all patients treated for a lefthemispheric infarct between the age of 2 months and 17 years. All
patients with documented aphasia in the acute phase were asked to
complete a short questionnaire regarding language functions (production, comprehension, reading, and writing). Results: Of the 35 patients
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
addressed, 24 patients (69%) returned the questionnaire. One patient
was deceased, for another patient no current address could be obtained.
For the whole group, the majority of patients reported “no” (13/24) or
“some” (7/24) language problems, only 3 of 24 reported considerable
problems (in more than one area). All six patients who had suffered the
infarct before the age of 5 years reported no language problems, two
patients who were 5 years old at the time of the infarction reported
“some” problems. Considerable problems were reported only by patients aged 7 years and older. Discussion: Up to the age of 4 years, good
recovery of language function seems to be the rule, even after extensive
left-hemispheric infarcts. After that age, residual aphasic symptoms may
persist. Obviously, the time frame in which an effective right-hemispheric language reorganization is possible seems to close around the
age of 5 years. Additional factors, such as epilepsy and intellectual
abilities, must be considered in future studies.
P055
Symptomatic Obstruction of the Sigmoid Sinus
by a Small Epidural Hematoma
Lindner C.1, Schwier F.2, Hahn G.3, Schackert G.1
1
Klinik und Poliklinik für Neurochirurgie,
Universitätsklinikum Carl Gustav Carus, Dresden,
Germany, 2Klinik und Poliklinik für Kinderchirurgie,
Universitätsklinikum Carl Gustav Carus, Dresden,
Germany, 3Institut und Poliklinik für radiologische
Diagnostik, Universitätsklinikum Carl Gustav Carus,
Dresden, Germany
The case of a small traumatic left occipital epidural hematoma (EDH) in a
4-year-old boy is presented. Magnetic resonance (MR) venography
revealed complete compression of the left sigmoid sinus resulting in
headache and vomiting. After evacuation of the hematoma, the symptoms recovered promptly and the flow in sigmoid sinus normalized.
Clinicians should be aware of the local effects of a small EDH leading to
complete sinus compression. Evacuation of the hematoma using a small
targeted craniotomy leads to a complete symptom relief. Introduction:
The main causes of cerebral venous sinus thrombosis (CVST) are
dehydration, infection, prothrombotic states, and chronic systemic
diseases. CVST as a result of trauma is rare and etiologies range from
mechanical falls with or without skull fracture, firework explosions,
gunshots, and blunt trauma to the head and closed head injury. The
patients may present with a variety of symptoms including irritability,
headache, seizure, cranial nerve palsies, and coma, we present the case
of a small circumscribed traumatic EDH at the left sigmoid sinus
resulting in complete sinus compression. Case report: A 4-year-old
boy presented to our hospital after a chair fall. He suffered from
headache, decreased appetite, and vomiting. On examination, a left
parieto-occipital subgaleal hematoma was seen. The initial low dose
computed tomography scan demonstrated a small right suboccipital
EDH without a skull fracture. An MRI scan was performed and showed a
20 ' 21 ' 12 mm EDH located at the sinus angle with MR venography
demonstrated complete obstruction of the left sigmoid sinus by a local
mass effect. During the next 24 hours, the headache and vomiting
continued. After informed consent was obtained from the parents a
small targeted craniotomy over the EDH was performed. Intraoperative
a skull fracture was seen but the confluence of transverse sinus and
sigmoid sinus was intact. The EDH was under significant pressure and
could be completely evacuated. After the procedure, the patients’
symptoms resolved immediately. Postoperative MRT and MR venography demonstrated complete removal of the hematoma with a normal
flow in the sigmoid sinus. After 8 days, the boy was discharged home free
of complains. Conclusion: We propose that a basilar skull fracture in the
region of temporal or occipital bone should be considered as a risk factor
for the development of transverse/sigmoid venous sinus obstruction
and may be an underestimated finding. From this case, we conclude that
surgical removal of EDH with decompression of a completely obstructed
venous sinus can lead to immediate reperfusion and complete symptom
relief. By pre- and postoperative venography obstruction and reperfusion of the sinus can be securely detected.
Abstracts
S41
Munich, 17th to 19th September 2014
P056
Diagnosis Allows Effective Reintegration of a
Child with Narcolepsy
Lübbig A.1, Ziegler S.1, Gebert R.1, Bernotat J.2, Staudt M.1
1
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurologische Rehabilitation, Epilepsiezentrum für Kinder
und Jugendliche Vogtareuth, Germany, 2Klinikum
Traunstein, Klinik für Kinder-und Jugendmedizin,
Traunstein, Germany
P057
Congenital Cataract Facial Dysmorphism
Neuropathy Syndrome: Differential Diagnosis
of Bilateral Congenital Cataract
Lüsebrink N.1, Moein G.1, Kieslich M.1
1
Klinik für Kinder- und Jugendmedizin
Universitätsklinikum der Goethe-Universität, Schwerpunkt
Neurologie, Neurometabolik und Prävention, Frankfurt,
Germany
When congenital cataract is present, the differential diagnosis comprises infectiological, metabolic, and genetic disorders. A definitive
classification can often only be made when additional symptoms
develop. We present a girl of Roma origin with bilateral congenital
cataract and progressive neurodevelopmental retardation who was
diagnosed with Congenital Cataract, Facial Dysmorphism, and Neuropathy (CCFDN) syndrome. This autosomal recessive disorder is a clinical
differential diagnosis of Marinesco-Sjögren syndrome. It has been
diagnosed in Roma and Sinti families only and represents one of the
most frequent causes of congenital cataract in this ethnic group. It
should therefore be sought out specifically by genetic testing of the
CTDP1 gene when the adequate clinical picture is present.
Lutz S.1, Della Marina A.1, Fleischhack G.2, Müller O.3,
Schara U.1
1
Department of Pediatric Neurology, University of Essen,
Germany, 2Division of Pediatric Oncology, Department of
Pediatrics III, University of Essen, Germany, 3Department of
Neurosurgery, University of Essen, Germany
Background: Inborn errors of neurotransmission and decreased function of the dopaminergic and serotoninergic systems could often lead to
movement disturbances and impaired development. The diagnosis is
made by examination of the cerebrospinal fluid (CSF) and in many cases
by genetic analysis. Besides genetical causes also parainflammational
causes are known. A relationship between brain tumors like an oligoastrocytoma and neurotransmitter, respectively, Dopa-responsive disturbances is not known so far. Case Report: A now 18-year-old young man
was first presented at the age of 2 years due to developmental delay. At
the age of 4 years, an ataxia was remarkable. In the further course, a leftsided accentuated spastic-dystonic movement abnormality, an inner ear
hearing loss, and a restrictive ventilation problem were found and in
spite of normal magnetic resonance imaging (MRI) a cerebral palsy was
diagnosed. At the age of 8 years, a second MRI showed a left-sided
subcortical gray matter change and a focal cortical dysplasia (FCD) was
suspected. This finding was stable over 10 years. In the meantime, the
boy was nearly unable to walk independently and became wheelchair
dependent. CSF examination showed a decreased homovanillic acidand 5-hydroxyindoleacetic acid-level. After substitution with Levodopa
(5 mg/kg/d), the patient improved suddenly and was able to walk again
independently. A phenylalanine challenge was without pathological
results and could not confirm a Segawa disease. Meanwhile, focal
epilepsy marked by aggression and disturbance of the short lasting
memory was remarkable, it was successfully treated with levetiracetam.
In the course of reevaluation, several MRIs were performed and the FCD
has been stable until the age of 15 years. At the age of 18 years, the MRI
showed a remarkable progress in size and dimension, histology showed
an oligoastrocytoma WHO grade II, which was removed subtotally. Four
months after the resection, controls of MRI have shown no growth of the
tumor’s rest. Conclusion: Disturbances of neurotransmission with a
broad spectrum of symptoms are known, their causes can be variable.
Because of the remarkable effects of Levodopa in our patient, but a
normal phenylalanine challenge, no further genetic analysis was performed. No relation between this brain tumor and a movement disorder
could be made. Our patient relies on Levodopa leading to dramatical
improvement of independent walking. In contrast, a dystonic component and the residual findings caused by oligoastrocytoma and its
subtotal resection remain.
P059
Klinefelter Syndrome Misdiagnosed As
Hereditary Neuropathy
Lutz S.1, Schroers E.1, Della Marina A.1, Wieczorek D.2,
Schara U.1
1
Division of Pediatric Neurology, Department of Pediatrics
I, University of Essen, Germany, 2Institute of Human
Genetics, University Hospital Essen, University of DuisburgEssen, Essen, Germany
Background: Hereditary sensory motor neuropathies (HMSN) are the
most common inherited neurologic disorders with a prevalence of
approximately 17 to 40/10,000. The course is variable and could be
mild to severe. Most of the patients stay mobile for their whole life.
Diagnosis is made by analysis of nerve conduction velocities and by
genetic testing. The Klinefelter syndrome is the most common chromosomal aberration in males; it shows signs both a tall habitus mostly
started with puberty, hormonal changes, and small testicles. Neurological findings are decreased muscle tone and sometimes cognitive impairment. An association of sensorimotor neuropathy and Klinefelter
syndrome is less known. Case Report: A 10 year-old-boy was presented
because of the generalized strength reduction, intolerance of endurance, and myalgia. The examination revealed a thin muscular relief,
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Background: We report the case of a 10-year-old boy with a decline of
school performance, attention deficits, occasional loss of consciousness,
and weight gain. The anamnestic hint of cataplectic attacks paved the
way for a breakthrough diagnosis. Already a few months after narcolepsy was diagnosed, there was a tremendous improvement in the family
and school situation as now an adequate medical and psychological
treatment had become available. Case History: Since starting at school,
the boy presented an increasing attention deficit, aggressive behavior,
drop of power, moments of suddenly falling asleep, as well as social
isolation. The youth-welfare services were informed by the school
director who had suspected deprivation. After an attention deficit
disorder and emotional disorder had been diagnosed, a treatment
with methylphenidate and psychotherapy was begun without lasting
improvement. The patient ran through four class changes in 3 years of
school without resolution of difficulties. In a highly tense social situation, a new medical check up was started. Magnetic resonance imaging
and electroencephalography were normal. Only after direct questioning,
the mother described bizarre mouth movements and laughing as well as
loss of posture with preserved consciousness. In the sleep laboratory,
the diagnosis narcolepsy with cataplexy was confirmed. A multiple
sleep latency test showed shortened latencies in sleep-onset-rem in
each episode and a pathologic somnogram. Cataplectic attacks were
documented as wells as sleep paralysis and hypnopompic hallucinations
were found. The genetic predisposition for narcolepsy was proven
(DBQ*0602). Once a stimulation therapy, psychotherapy, education of
parents had been initiated with the help of professional school advisers,
the patient managed to reattend his previous school class again after 6
months. Conclusion: Identifying the chronic illness narcolepsy with
cataplexy and effective education of the social and personal environment lead to a tremendous improvement in the quality of life after
methylphenidate therapy and adequate psychotherapy were begun.
P058
Levodopa-Dependent Movement Disorder and
Oligoastrocytoma Double Trouble or
Dependent from Each Other?
S42
Abstracts
Munich, 17th to 19th September 2014
Munich, 17th to 19th September 2014
proximal-accentuated strength reduction, contractures of the upper
ankle joint, and generalized are flexia. Sensibility and vibration feeling
were intact. Nerve conduction velocities showed signs of axonal damage
and sensible evoked potentials a retardation of the tibial nerve. Because
of suspicion of a hereditary neuropathy (e.g., HMSN) genetic testing was
initiated and included the MFN2, MPZ/P0, and the Cx2 gene, after a spinal
muscular atrophy has been excluded. No positive results could be found.
At the age of 15 years, the boy showed a tall habitus and small testicles in
contrast to the secondary sex characters. A Klinefelter syndrome was
suspected and could be confirmed by chromosomal examination (karyotype 47, XXY). Conclusion: Affection of the peripheral nerves in
patients with a Klinefelter syndrome is little known, only few articles
can be found in the literature. In male patients with signs of peripheral
neuropathy, where otherwise a diagnosis is not to be confirmed, the
possibility of a Klinefelter syndrome with coexisting peripheral neuropathy has to be considered.
P060
Clinical Application of Somatosensory-Evoked
Potentials in Pediatrics
Maier O.1, Novak S.1, Peterli J.1
1
OstSwitzerlander Kinderspital St. Gallen, Zentrum für
Kinderneurologie, Entwicklung und Rehabilitation (KERZentrum), St. Gallen, Switzerland
Introduction: Somatosensory-evoked potentials (SEP) allow evaluation
of the functional integrity of the somatosensory system from the
peripheral nerve to the cerebral cortex. Although in childhood the
clinical application of SEPs are less well established than in the adult
population this is a useful method in a variety of pediatric neurologic
conditions. Method: Clinical application of SEP in pediatric neurology is
described with the experience of a pediatric neurophysiologic unit and
the literature is reviewed. Result: SEPs are useful in pediatrics for the
evaluation of peripheral pathology, spinal cord lesions, lesions of the
cervicomedullary junction, brain stem lesions, and cortical lesions. SEPs
can be used in predicting outcome in perinatal asphyxia or in a coma.
Maturational changes and normative data have to be considered in
clinical application. The methodology should be adapted to the need of
children. Conclusion: SEPs in pediatrics are a reasonable diagnostic tool,
if there is a clear clinical indication. Interpretation must be done in the
clinical context. Age-dependent normative values have to be considered.
Methodology has to be adapted to the children’s needs.
P061
Diagnostic Difficulties in a Child with Tay-Sachs
Disease
Makowski C.1, Baumkötter J.2, Haack T.3, Burdach S.2
1
Kinderklinik München-Schwabing, Technische Universität
München, Neuropädiatrie, München, Germany,
2
Kinderklinik München-Schwabing, Technische Universität
München, Pädiatrie, München, Germany, 3Institut für
Humangenetik, Technische Universität München, München,
Germany
Case Presentation: We present a girl with severe developmental delay
with regression, leukodystrophy, epileptic encephalopathy, blindness,
and a cherry red macula spot. Metabolic testing was normal apart from
an elevated chitotriosidase. Total hexosaminidase was normal. We
suspected a GM2-gangliosidosis type Tay-Sachs disease and retested
the total hexosaminidase activity and hexosaminidase A separately and
found a very low hexosaminidase A activity, which confirmed the
diagnosis of Tay-Sachs disease. Exome sequencing identified a previously reported pathogenic homozygous missense mutation (c935T>G,
pMet312Arg; CM930397) in HEXA A, thereby, confirming the diagnosis
on the molecular level. Conclusion: In clinical suspicion of Tay-Sachs
disease, it is useful not only do test the total hexosaminidase but to test
hexosaminidase A separately.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
P062
A Dystroglycanopathy with Multicystic
Leukodystrophy with a Novel Homozygous
Dystroglycan Mutation in DAG1 Gene
Marquard K.1, Geis T.2, Reihle C.1, Schirmer S.3, Hehr U.3,
Blankenburg M.1
1
Neuropädiatrie, Olgahospital, Klinikum Stuttgart,
Germany, 2Neuropädiatrie, Klinik St. Hedwig,
Universitätskinderklinik Regensburg, Germany, 3Zentrum
für Humangenetik, Regensburg, Germany
Introduction: Dystroglycan has a central position in the cytoskeleton.
Until now, defective dystroglycan is induced by disturbance of Oglycosylation of α dystroglycan with a broad clinical spectrum of
dystroglycanopathies. Muscle-eye-brain (MEB) disease and WalkerWarburg syndrome are the most severe course. A primary dystroglycanpathies with a mutation in the encoding gene DAK1 was described in
only one patient before. Case Report: We describe affected Libyan
siblings with nonconsanguine parents, clinical evaluation with 2 years
8 months and 3 years 7 months. Both children have severe developmental delay. They were not able to speak or to walk, but both can eat
and drink by themselves. We found macrocephalie, congenital cataract,
and elevated creatinine kinase values approximately 1,500 U/L. Muscle
biopsy was performed in the younger girl with defective visualization of
α dystroglycan by histochemical techniques. Cerebral magnetic resonance imaging shows structural changes of brain stem and cerebellum
as describe previously in MEB. Beside these changes, we found in both
children severe white matter abnormalities with large bilateral subcortical cysts so in dystroglycanopathies not described before. Conclusion:
We describe a new mutation in DAG1 gene encoding for dystroglycan.
Only one pathogen mutation is described in this gene before. Most
dystroglycanopathies are secondary due to defects in glycosylation of
dystroglycan. The clinical phenotype of the new mutation has features
of MEB disease. But also, we found severe abnormalities of white matter
with large subcortical cysts never seen in dystroglycanopathies before
and extending the clinical spectrum of this entity of disease.
P063
Effects of Rapamycin on Monocytes from
Pediatric Patients with Tuberous Sclerosis
Meyer C.1, Kurlemann G.2, Sauter M.3, Kreuzaler P.4, Doganci
A.5, Gehring S.6, Hertzberg C.7, Zepp F.6, Knuf M.8
1
Universitätsmedizin der Johannes Gutenberg-Universität,
Pädiatrische Immunologie Mainz, Mainz, Germany, 2Klinik
für Kinder- und Jugendmedizin, Universitätsklinikum
Münster, Allgemeine Pädiatrie, Neuropädiatrie, Münster,
Germany, 3Medizinische Klinik u. Piliklinik IV, Klinikum der
Universität München, Nephrologisches Zentrum, München,
Germany, 4Zentrum für Kinder u. Jugendmedizin des
Univrsitätsklinikums Gießen, Abteilung Neuropädiatrie,
Sozialpädiatrie und Epileptologie, Gießen, Germany,
5
Zentrum für Kinder u. Jugendmedizin der
Universitätsmedizin der JohGutenberg Uni Mainz,
Pädiatrische Immunologie Mainz, Mainz, Germany,
6
Zentrum für Kinder u. Jugendmedizin der
Universitätsmedizin der JohGutenberg Uni Mainz, Mainz,
Germany, 7Vivantes-Klinikum Neuköln,
Behandlungszentrum Entwicklung u. Neurologie des
Kindes- u. Jugendalters, Berlin, Germany, 8Dr. HorstSchmidt Kliniken, Klinik für Kinder u. Jugendmedizin,
Wiesbaden, Germany
Objective: Genetic defects in TSC1/TSC2 genes have been recognized as
the leading cause for tuberous sclerosis (TS) complex syndrome, clinically characterized by epileptic seizures, benign brain tumors, and
malformations. With defective TSC1/TSC2 gene expression the downstream factor mammalian target of rapamycin (mTOR) is activated,
which is a powerful modulator of diverse cellular processes including
effects on the immune system. Innate immune functions, specifically the
inflammatory responses and the effects of rapamycin on monocytes in
pediatric TS patients have not yet been described. Methods: We
characterized the expression levels of 84 genes related to inflammation
and autoimmunity by using polymerase chain reaction array technology
Abstracts
S43
Munich, 17th to 19th September 2014
P064
Endoscopic Ventriculostomy in a 22-Month-Old
Girl after Fetal Surgery for Lumbar
Myelomeningocele
Nögel S.1, Hirsch A.1, Eyüpoglu I.2, Lorenz I.1, Stadlbauer A.2,
Trollmann R.1
1
Kinder-und Jugendklinik, Universitätsklinikum,
Neuropädiatrie und Sozialpädiatrie, Erlangen, Germany,
2
Neurochirurgische Klinik, Universitätsklinikum, Erlangen,
Germany
Background: In most cases of myelomeningoceles (MMC), endoscopic
third ventriculostomy (ETV) for the treatment of hydrocephalus is
limited by a Chiari-II malformation. ETV in infants with MMC in the
first year of life is significantly less successful than ventricular shunt
placement (22.6 vs. 57.5% after 1 year observation).1 In older children,
the success rate of ETV improves.2 Case Report: A 3-year-old girl with a
lumbar MMC underwent fetal surgery at 25 weeks of gestational age.
The MMC was covered with a patch. Although the patient did not have a
Chiari-II malformation, she developed a progressive hydrocephalus
during the first year of life. Cranial magnetic resonance imaging gave
suspicion of an aquaeductal stenosis. The suspicion was confirmed by
cerebrospinal fluid flow measurement. At the age of 22 months, the
patient underwent ETV. The patient has been without symptoms of
increased intracranial pressure since 19 months ago. Conclusion: After
fetal surgery of MMC, the risk of a hydrocephalus with increased
intracranial pressure development remains. In the case of hydrocephalus and no radiologic signs of a Chiari-II malformation, aquaeductal
stenosis should be taken into consideration because ETV can be viewed
as a promising therapy option.
References
1 Jernigan SC, Berry JG, Graham DA, Goumnerova L. The comparative
effectiveness of ventricular shunt placement versus endoscopic third
ventriculostomy for initial treatment of hydrocephalus in infants. J
Neurosurg Pediatr 2014;13(3):295–300
2 Koch-Wiewrodt D, Wagner W. Success and failure of endoscopic
third ventriculostomy in young infants: are there different age
distributions? Childs Nerv Syst 2006;22(12):1537–1541
P065
15 Years of Pediatric Epilepsy Surgery in
Vogtareuth
Pascher B.1, Pieper T.1, Holthausen H.1, Karlmeier A.1,
Kudernatsch M.2, Kolodziejczyk D.2, Winkler P.1, Blümcke I.3,
Staudt M.1
1
Schön Klinik Vogtareuth, Klinik für Neuropädiatrie und
Neurorehabilitation, Epilepsiezentrum für Kinder und
Jugendliche, Vogtareuth, Germany, 2Schön Klinik
Vogtareuth, Klinik für Neurochirurgie und
Epilepsiechirurgie, Vogtareuth, Germany,
3
Universitätsklinikum Erlangen, Institut für
Neuropathologie, Erlangen, Germany
From November 1998 to December 2013, 430 children, adolescents, and
young adults with drug-resistant focal epilepsies have undergone
epilepsy surgery at our center. Here, we report the demographic data,
etiologies, surgical procedures, and seizure outcomes (minimum followup 6 months, average 6.8 years). Epilepsy onset ranged from 1 month to
20 years (mean, 3.3 years), age at surgery ranged from 9 months to 34
years (mean, 9.2 years). Etiologies were focal cortical dysplasias (n ¼
179), cystic-gliotic lesions (n ¼ 88), tumors (n ¼ 64), phakomatoses (n ¼
22), hippocampal sclerosis (n ¼ 20), other cortical malformations (n ¼
33), Rasmussen encephalitis (n ¼ 9), nonlesional (n ¼ 6), other (n ¼ 9).
Surgical procedures were hemispherotomies (n ¼ 92), frontal lobe
resections (n ¼ 60), temporal lobe resections (n ¼ 87), bi- and multilobar
resections (n ¼ 148), subtotal hemispheric resections (n ¼ 18), other (n
¼ 25). A second operation was performed in 49 and a third operation in 6
patients; overall, 31 of these 49 patients (63%) benefitted from the
reoperation. Epilepsy outcome (Engel classification): Seizure free (1a)
57%, auras only (1b) 7%, > 90% seizure reduction (2) 11%, > 50% seizure
reduction (3) 11%, unchanged (4) 10%, no postoperative follow-up yet
4%. Conclusions: Overall, 75% of our patients had a favorable seizure
outcome (Engel 1+2), despite the complexity of our cohort (60% multilobar resections and hemispherotomies). Outcome depended on etiology:
Favorable outcome was less frequent in patients with focal cortical
dysplasias (68%) than in the other patients (79%).
P066
4H-Syndrome: A Common Cause for
Hypomyelination
Rauscher C.1, Wolf N.2, Vervenne-van Spaendonk R.3,
Boltshauser E.4
1
Paracelsus Medizinische Privatuniversität, Univ.-Klinik für
Kinder-u.Jugendheilkunde, Salzburg, Austria, 2VU
University Medical Center, Child Neurology, Amsterdam,
The Netherland, 3VU University Medical Center, Clinical
Genetics, Amsterdam, The Netherland, 4Medizinische
Klinik, Universitätskinderklinik, Zürich, Switzerland
Background: Hypomyelination with hypodontia and hypogonadotropic
hypogonadism (HHHH) is an inherited autosomal recessive disease,
which was first recorded in four children1 and four adults2. The patients
all demonstrated a progressive ataxia as well as cerebellar atrophy.
Mutations in POLR3A or POLR3B gene have been identified as the cause.
It is now known from a larger collective that not only a genetic but also a
clinical heterogeneity exists. Hypodontia and hypogonadism are not
always present. This report describes a 16-month-old patient. Case
Report: The child was evaluated because of ataxia and increased
“tremors” of his whole body and head. At the time of birth, six teeth
were already broken (in the meantime four had already fallen out, no
new tooth has broken). When the child was 10 months’ old, his mother
first noticed the intermittent shaking which increased during infection
but was followed by partial improvement. In the neurological examination, the patient demonstrated both hypotonia focused around the torso
also ataxia of the extremities and torso. He was able to pull himself into a
standing position and to stand with his knees extended. Even when the
head was turned to the left, his gaze was to the right. In the cerebral
magnetic resonance imaging (MRI), there was a clear global myelin
deficit. The ventrolateral thalamus had a relatively T2-hypointense
signal. The posterior limb of the internal capsule and part of the optic
radiation were myelinated and the cerebellum was mildly atrophied.
The combination of “hypomyelination” (still of young age), “dentes
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
to assess monocytes from TS patients (n ¼ 16) in comparison to
monocytes from age-matched healthy subjects (n ¼ 20) after in vitro
overnight cultivation in the presence of lipopolysaccharides (LPS) or LPS
+ rapamycin. Results: LPS induced a more vivid gene expression in
monocytes from TS patients compared with healthy subjects, specifically for CCL24, CXCL10, IL-6, IL-10, and IL-1B. In the presence of LPS +
rapamycin monocytes from TS patients’ gene expression pattern was
clearly different from age-matched healthy subjects. In addition, agespecific differences were obvious in monocytes from TS patients, when
comparing the gene expression levels for patients at age of 0 to 5 years to
those 6 to 11 years, the latter group presented with significantly higher
expression levels for IL-6, IL-1A, IL-1B, RIPK2, but also IL-10. Conclusion:
The detected effects of LPS, and even more those of LPS + rapamycin on
monocytes from TS patients suggested, that in the absence of or with
limited or defect TSC1/TSC2 gene products the processes connected to
inflammation are distinct from those in monocytes from healthy subjects. We identified an age-related reaction upon application of rapamycin, which indicates a need for further investigations in the action
mechanisms of rapamycin in the context of the developmental dynamic
of the child organism. Our findings represent a first model to decipher
these various, still unknown fields of action of rapamycin not only for
monocytes, but presumably for other cell systems, including TS typical
tumors.
S44
Abstracts
Munich, 17th to 19th September 2014
natales” and cerebellar atrophy prompted us to genetically test for 4H
syndrome. Through our attempts, we were able to detect the two
heterozygous mutations in the compound POLR3B gene (c.1568T> A;
p.Val523Glu and c.2570 +1 G> A). A study of the hormonal status has not
yet been undertaken. Conclusion: When hypomyelination appears on
an MRI with cerebellar atrophy and progressive ataxia one should
always look at dental development and if abnormal one should test
for mutations in the POLR3A and POLR3B gene.
P068
Munich, 17th to 19th September 2014
Reference
1 Wolf NI, Harting I, Boltshauser E, et al. Leukoencephalopathy with
ataxia, hypodontia, and hypomyelination. Neurology 2005;64
(8):1461–1464
2 Timmons M, Tsokos M, Asab MA, et al. Peripheral and central
hypomyelination with hypogonadotropic hypogonadism and hypodontia. Neurology 2006;67(11):2066–2069
P067
A Novel Phenotype: Microcephaly, Intellectual
Disability, and Mid-hindbrain Defect
Ravindran E.1, Hu H.2, Kraemer N.1, Ninnemann O.3,
Musante L.2, Boltshauser E.4, Schindler D.5, Ropers H.2,
Wienker T.2, Hubner C.6, M. Kaindl A.1
1
Institut of Cell Biology and Neurobiology and Department
of Pediatric Neurology, Charité, Berlin, Germany, 2Max
Planck Institute for Molecular Genetics, Berlin, Germany,
3
Institut of Cell Biology and Neurobiology, Charité, Berlin,
Germany, 4Department of Pediatric Neurology, University
Children’s Hospital of Zurich, Zürich, Switzerland, 5Institut
für Humangenetics, Würzburg, Germany, 6Department of
Pediatric Neurology, Charité, Berlin, Germany
Introduction: During development, the mesencephalon and rhomboencephalon are derived from two developmental compartments of the
neural tube. The midbrain-hindbrain border (MHB) is defined by the
controlled expression of genes, which is crucial for the cerebellar and
brain stem development. Hindbrain is composed of three major parts:
pons, medulla oblongata, and cerebellum. During development, the
anterior part of the neural tube is divided into different segments, or
rhombomeres, which possess a localized gene expression. This segmentation is highly important for the proper development of various brain
regions and group of proteins are known to contribute to the localized
gene expression. As specifically controlled gene expression gives rise to
distinct midbrain-hindbrain structures, the developmentally related
structures are often coaffected in diseases that are associated with early
midbrain-hindbrain developmental disorders. Objective and Methods:
In this study, we describe the detailed clinical and radiological phenotype of two affected children of a consanguineous family of KurdishTurkish descent with microcephaly and intellectual deficit. The family
was further studied by whole exome and Sanger sequencing, and mRNA
and protein levels of the candidate gene were evaluated through
quantitative polymerase chain reaction and western blot. The effect of
the identified mutation was also assessed on a cellular level through
immunocytochemistry using lymphoblastoid cells from patients and
controls. Results and Outlook: The phenotype of our patients includes
facial dysmorphism with long eyelashes, horizontal pendular nystagmus, strabismus, hyperopia, retinal dystrophy, muscular hypotonia, and
disturbance in fine motor movements. Intellectual deficit (intelligence
quotient < 50) and speech delay was also observed. Cranial magnetic
resonance imaging (MRI) revealed microcephaly and cerebellar hypoplasia in patients. We identified a homozygous nonsense mutation in a
gene not linked to any disease so far and found both mRNA and protein
levels to be reduced in patient samples when compared with controls.
This indicates a nonsense-mediated RNA decay. At a cellular level,
patient cells displayed cell cycle apparatus defects. We are currently
studying the pathomechanism underlying the novel disease and are
searching for further patients with a similar midbrain-hindbrain defect.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
It Is All in the Head: Clinical Register for Patients
with Traumatic Brain Injury: TBI Register
Rödiger M.1, Linden T.1, Althaus J.1, Debus O.2, Dugas M.3,
Fiedler B.1, Petershofer A.4, Schulte C.H.5, Storck M.3, Teetz
K.6, Völzke V.4, Wietholt G.8, Omran H.1
1
General Paediatrics, Dept. For Neuropaediatrics, Clinic for
Child and Youth Medicine, University Clinic of Münster,
Münster, Germany, 2Child and Youth Medicine, Clemens
Hospital Münster, Münster, Germany, 3Institute for Medical
Informatics, University of Münster, Münster, Germany,
4
HELIOS Clinic Holthausen, Special Clinic for Neurosurgical
and Neurological Rehabilitation, Hattingen, Germany, 5C/O
Technology Promotion Münster GmbH, Health Region
Münsterland, Münster, Germany, 6Centre for Out-Patient
Rehabilitation, Hattingen, Germany, 7Paediatric
Neurological Aid Münster e.V., Münster, Germany
Background: Every year approximately 280,000 people suffer from
traumatic brain injury in Germany. About 72,000 children and adolescents are affected, which is a very high proportion. The majority of
patients with traumatic brain injury (TBI) suffer from permanent
disabilities as a consequence of this injury. The likelihood of experiencing a TBI is twice as high for boys than for girls. This gender difference
becomes more marked with increasing age, presumably due to the
gender-specific propensity to risk taking in sports and leisure activities.
Whether or not gender-specific factors also influence the outcome
regarding mortality and neurocognitive functions or rehabilitation
potential has not yet been adequately investigated in Germany. In
emergency care, there are also deficits in the coordination of processes
across all sectors and in secondary treatment (e.g., by general practitioners and in [early] rehabilitation) which leads to duplication of
examinations and treatment. There is currently a lack of systematic
documentation of individual cases of medium and severe TBI on
different levels of care. Method: Detailed data on accident mechanism,
lesions, laboratory parameters and functional deficits and their course
are recorded anonymously and analyzed in the TBI Register of the
University Clinic Münster in cooperation with partners from the Emergency Medical Care (UKM), Early Rehabilitation (Clemenshospital Münster), continued rehabilitation (Helios Clinic Hattingen), and
coordinators of aftercare (Centre for out-patient rehabilitation Münster,
Pediatric Neurological Aid, Sociopediatric Centres, NRW). The project is
funded by the Ministry for Health, Equality, Care, and Aging of the State
of North-Rhine Westphalia as part of the “IuK & Gender Med. NRW”
competition. Objectives: Analysis of register data are of prime importance for the evaluation of prevention measures and provides an
information basis for optimizing patient care. The structure and process
quality along the existing treatment chain including interfaces between
emergency treatment and rehabilitation facilities and secondary care
are mapped to optimize the quality of TBI patient care.
P069
MPAN: A Rare Cause for Spastic Cerebral Palsy,
Bilateral Optic Atrophy, Elevated Creatine
Kinase and Psychiatric Symptoms Caused by
Mutation in C19orf12
Ross S.1, Schagerl M.1, Lorenz I.1, Hoffjan S.2, Trollmann R.1
1
Kinder- und Jugendklinik, Neuropädiatrie, Erlangen,
Germany, 2Humangenetik, Bochum, Germany
Introduction: Autosomal recessively inherited MPAN (mitochondrial
membrane protein-associated neurodegeneration) is a recently discovered subtype of NBIA (neurodegeneration with brain iron accumulation). The median age of onset of first symptoms is 11 years. First signs
are gate disturbances and cognitive failure. Typically, patients suffer
from progressive spastic cerebral palsy, bilateral optic atrophy, and
Parkinson-like symptoms. At the terminal stage, patients might lose
their ability to walk, show severe dementia, get bilateral spastic cerebral
palsy, dystonia, Parkinsonism as well as further psychiatric symptoms
and consciousness disturbances. To date, only symptomatic treatment is
available for this disease. At the onset of disease, our patient was 10
years’ old, and only 2 years later, she showed almost all of the
characteristic symptoms. Case Report: At the age of 10 years, the
Abstracts
S45
Munich, 17th to 19th September 2014
References
1 Schneider SA, Dusek P, Hardy J, Westenberger A, Jankovic J, Bhatia KP.
Genetics and Pathophysiology of Neurodegeneration with Brain Iron
Accumulation (NBIA). Curr Neuropharmacol 2013;11(1):59–79
2 Hogarth P, Gregory A, Kruer MC, et al. New NBIA subtype: genetic,
clinical, pathologic, and radiographic features of MPAN. Neurology
2013;80(3):268–275
3 Schulte EC, Claussen MC, Jochim A, et al. Mitochondrial membrane
protein associated neurodegenration: a novel variant of neurodegeneration with brain iron accumulation. Mov Disord 2013;28
(2):224–227
P070
Primary Microcephaly, Muscle Hypotonia, and
Global Developmental Delay: A Case of an
Exceptional Clinical Manifestation of
Maternally Inherited Mitochondrial T8993T>G
Mutation in MT-ATP6 Gene
Schallner J.1, Kinder S.1, Hahn G.2, DiDonato N.3, Jackson S.4,
von der Hagen M.1
1
Universitätsklinikum Carl Gustav Cars der TU Dresden,
Neuropädiatrie, Dresden, Germany, 2Insitut und Poliklinik
für radiologische Diagnostik, Dresden, Germany, 3Institut
für Klinische Genetik Medizinische Fakultät CGC TU
Dresden, Dresden, Germany, 4Klinik und Poliklinik für
Neurologie Universitätsklinikum Carl Gustav Cars der TU
Dresden, Dresden, Germany
Objective: The m.8993T>G mutation in the gene MT-ATP6
(MIM:516060) which encodes subunit six of complex V (adenosine
triphosphate synthase) of the mitochondrial respiratory chain is one of
the more common disease associated mutations in mitochondrial DNA
(mtDNA). The mutation is heteroplasmic, occurring together with wildtype mtDNA in affected individuals, and is associated with two different
clinical phenotypes: NARP (neuropathy, ataxia, and retinitis pigmentosa) or MILS (maternally inherited Leigh syndrome), with the latter
usually associated with a high mutation load. Case Report: Here, we
report the case of a 2-year-old girl with postnatal primary microcephaly
and muscle hypotonia. The infant is the only child of healthy, nonconsanguineous parents. At the age of 6 months, severe development
delay appeared. At the age of 20 months, extensive clinical diagnostics
revealed elevated serum lactate, brain atrophy in magnetic resonance
imaging, and interictal epileptiform discharges. Polymerase chain reaction-restriction fragment length polymorphism analysis detected a high
load of the m.8993T>G mutation in blood, confirmed by sequencing.
Conclusion: Primary microcephaly is a rare manifestation of mtDNA
mutations, and has not yet been described in patients with the
m.8993T>G mutation. Genotype–phenotype correlations related to
the m.8993T>G mutation seem to be variable, and is not always
associated with typical features of MILS or NARP.
P071
Steroid-Responsive Encephalopathy with
Autoimmune Thyroiditis in Childhood: A Rarity
Scharf B.1, Köhler C.2, Tymann S.3, Udo M. K.4, Lücke T.2
1
General Paediatrics, University Children’s Hospital, Ruhr
University, Bochum, Germany, 2Department of
Neuropaediatrics with Social Paediatrics, University
Children’s Hospital, Ruhr University, Bochum, Germany,
3
Department of Paediatric Gastroenterology and
Hepatology, University Children’s Hospital, Ruhr University,
Bochum, Germany, 4Endocrinology, University children’s
hospital, Ruhr University, Bochum, Germany
We report the case of a 15-year-old girl, who pursuant to a generalized
seizure, exhibited symptoms of stupor, high fever, and uncontrolled
jerking. Since 1 month, a cervical soft-tissue swelling existed but it was
not diagnosed as a goitre. In addition, recurring cephalgia and nausea
were present in the weeks before the convulsion incident. Symptoms did
not stop under antiepileptic treatment and mechanical ventilation
became necessary. The neurological examination showed constricted
pupils and brisk deep tendon reflexes. Cranial magnetic resonance
imaging and cranial computed tomography were normal. Status of
cerebrospinal fluid was inconspicuous except for an elevated protein
(77 mg/dL); inflammation parameters, drug screening, retention values,
transaminases, and search for neurotropic viruses and bacterial pathogens were normal as well. An electroencephalography showed symptoms of a generalized slowing. Examination of thyroid function showed
signs of primary hypothyroidism (thyroid-stimulating hormone, 72.31
µIU/mL; fT3, 1.63 pg/mL; and fT4, 0.38 ng/dL) accompanied by elevated
thyroglobulin antibodies and thyroid peroxidase auto-antibodies (antiTPO) (378 U/mL respectively 536 U/mL). Thyroid sonography showed
heterogeneous, hyperechogenic parenchymal pattern indicating thyroiditis. Under assumption of steroid-responsive encephalopathy with
autoimmune thyroiditis (SREAT), a therapy with cortisone and Lthyroxine and levetiracetam as anticonvulsive treatment was started.
This treatment caused a fast improvement of the symptoms, in particular to a rapid lowering of the fever. The patient was extubated after 2
days, and cleared up slowly. After 1 week, she was able to walk again. The
patient was discharged after 10 days. After 3 weeks, the initiation of the
treatment a complete restitution ad integrum could be documented.
The SREAT is a rare disease particularly in childhood. Main symptoms
are myoclonus, gait disorders, seizures, and sleep disorders. Other
neurological symptoms such as visual and auditory hallucinations,
mood swings, and clouding of consciousness may occur. In case of an
unclear encephalopathy, SREAT should be taken into consideration. As
SREAT patients may also be euthyroid or even hyperthyroid, thyroid
auto-antibodies have to measure besides the typical thyroid parameters.
P072
Posterior Reversible Encephalopathy Syndrome
in Childhood
Schlachter K.1, Fleger M.1, Vonbank H.2, Ausserer B.3,
Wiest R.4, Huemer C.1
1
Akademische Lehrabteilung Kinder- und Jugendmedizin,
Neuropädiatrie, Landeskrankenhaus Bregenz, Austria, 2
MR-Institut Bregenz, Bregenz, Austria, 3Abteilung für
Kinder- und Jugendheilkunde, KH-Dornbirn, Austria,
4
Neuroradiologie Inselspital Bern, Switzerland
Acute headaches with remittent vomiting and seizures represent an
emergency in neuropediatric patients. Severe reversible posterior encephalopathy is a rare diagnosis in childhood. The literature provides
case reports to the course of adults. The term has been used first in 1996
by Hinchey on the occasion of a series of 15 cases. Those patients
exhibited a reversible syndrome with headache, neuropsychological
distinctive features, visual abnormalities (blurry gaze, visual hallucinations, visual neglect, hemianopia, and cortical blindness) and seizures.
The posterior reversible encephalopathy syndrome (PRES) is known
under merely different designations and a misnomer, because it is not
reversible in all of the cases, not always limited to the posterior regions
of the brain and the gray matter often is affected too. The causes are
versatile. Triggers primarily are chemotherapeutic agents and immunosuppressive drugs, renal diseases as well as accelerated blood pressure
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
patient presented with sudden falls, and examination showed bilateral
spastic cerebral palsy. Cranial magnetic resonance imaging showed
alterations in palladium and the crus cerebri. Creatine kinase was
elevated (max 273 U/L). In the muscle biopsy, fibers from type 1 were
predominant, there were scattered atrophic muscle fibers, and no
mitochondrial disease could be detected. At the age of 12 years, bilateral
optic atrophy was diagnosed. Cognitive testing (HAWIK IV) resulted in a
below average intelligence quotient score of 78. No known NBIAassociated mutations in PKAN2 and PLA2G6 genes were found. Analysis
of the C19orf12 gene revealed a homozygous Gly69Arg mutation. During
disease progression, the girl developed tremor, dysarthria, hypomimia,
partial aphasia, reduced control of impulses, social retraction, and
depressive symptoms. Conclusion: In patients with typical signs of
NBIA that lack common mutations such as PANK2, PLA2G6, or FA2H,
mutation analysis of the C19orf12 gene should be considered for
diagnostic confirmation of autosomal-recessive MPAN. Such a diagnosis
backup might facilitate genetical counseling and adequate symptomatically treat.
S46
Abstracts
Munich, 17th to 19th September 2014
Munich, 17th to 19th September 2014
with hypertensive crises. These are responsible for the development of a
vasogenic edema. Magnetic resonance imaging of the brain is the
favored modality of investigation. Cerebral edema involving the posterior regions of the cerebral hemispheres, particularly the posterior
parietal and occipital lobes, is seen as increased T2 and fluid attenuated
inversion recovery signal. Apparent diffusion coefficient maps show
increased signal, and diffusion weighted imaging images normal or
decreased signal intensity of lesions. These features can differentiate
between vasogenic cerebral edema in PRES. Prognostic crucial is a rapid
start of an efficient therapy (decline of the hypertension and stop of the
responsible medication). We report the case of a 14-year-old boy with
PRES within the frame work of an unknown hypertension before
admission to the hospital and a girl aged 16 years with unknown origin
who also presented with PRES. Furthermore, we want to give an
overview of the literature with a special attention to the publications
to PRES in children.
P073
Atypical Presentation of the GLUT-1 Deficiency
Syndrome with Cataract and Normal Glucose
Concentration in Cerebrospinal Fluid
Schmitz N.1, Blank A.1, Baz Bartels M.1, König R.2,
Kieslich M.1
1
Klinik für Kinder- und Jugendmedizin, Johann Wolfgang
Goethe-Universität, Neuropädiatrie, Frankfurt am Main,
Germany, 2Institut für Humangenetik, Johann Wolfgang
Goethe-Universität, Frankfurt am Main, Germany
Background: The SLC2A1 gene on chromosome 1 encodes a glucose
transporter in the blood-brain barrier. A defect of this gene is responsible for the glucose transporter 1 (GLUT-1) deficiency syndrome, a
metabolic disease which leads to an undersupply of glucose for the
brain. Main symptoms are infantile-onset seizures refractory to anticonvulsant medications, an acquired microcephaly, and developmental
delay and movement disorders. Other than the mentioned diseases,
there is a rare form of hereditary stomatocytosis, called stomatindeficient cryohydrocytosis, caused by a mutation in the same gene as
the mutation of the GLUT-1 deficiency syndrome. The patients show
anemia, a cataract, as well as neurological symptoms such as epilepsy,
developmental delay, and movement disorders. In our case report, we
present a new mutation of the SLC2A1 gene which includes symptoms of
both clinical pictures in the phenotypical spectrum. Case: We report on
a patient with a detected mutation in the SLC2A1 gene and clinical
symptoms of the GLUT-1 deficiency syndrome. Among the classical
symptoms such as infantile-onset epilepsy resistance to therapy, developmental delay, and movement disorders, there are also atypical
symptoms such as a cataract and splenomegaly. Other untypical diagnostic findings are normal glucose concentration in the cerebrospinal
fluid and the absence of secondary microcephaly. Conclusion: The
detected mutation extended the phenotypical spectrum of the known
mutations in the SLC2A1 gene. The differential diagnosis of infantileonset seizures refractory to anticonvulsant medications in combination
with cataract should contain the GLUT-1 deficiency syndrome. In
addition, normal concentration of glucose in the cerebrospinal fluid
in combination with earlier named symptoms should not be a criterion
of exclusion for the GLUT-1 deficiency syndrome in the potential
diagnosis. Furthermore, in a combination with anemia, cataract and
neurological symptoms, a mutation in the SLC2A1 gene should be
considered. Particularly, in regard to potential therapy with ketogenic
diet, it is to prove whether this form of treatment could influence the
neurological symptoms of patients with mutation in the SLC2A1 gene
and an atypical presentation of the GLUT-1 deficiency syndrome.
P074
Neurocognitive Plasticity in Frontotemporal
Aplasia: A Case Report
Schmitz-Peiffer H.1, Engellandt K.2, Reichmann H.1,
Hallmeyer-Elgner S.1
1
Universitätsklinikum Dresden Carl Gustav Carus, Klinik
und Poliklinik für Neurologie, Dresden, Germany,
2
Universitätsklinikum Dresden Carl Gustav Carus,
Abteilung Neuroradiologie, Dresden, Germany
In the presented case, we noticed the left-sided fronto-temporal arachnoid cyst with aplasia of the left temporal lobe and aplasia of the right
temporal pole as an incidental finding in a 34-year-old right-handed
high-school graduate with technical diploma complaining of vertigo
after right-sided posterior inferior cerebellar artery PICA infarction in
the context of a patent foramen ovale (PFO). The extensive frontotemporal aplasia did not harm the intellectual and mnestic sanity during
neuronal development. Thus, we assume that a compensation of material-specific abilities was ensured within remaining structures.
Tolosa Hunt Syndrome
P075
Schober H.1, Lütschg J.1, Doringer W.2, Staber H.3, Simma B.1
1
LKH Feldkirch, Kinder-und Jugendheilkunde, Feldkirch,
Austria, 2LKH Feldkirch, Radiologie, Feldkirch, Austria, 3LKH
Feldkirch, Augenheilkunde, Feldkirch, Austria
Introduction: Tolosa Hunt syndrome is characterized by periorbital pain
combined with palsy of the cranial nerves III, IV, or VI, which appears
simultaneously or within a period of 2 weeks. Magnetic resonance
imaging (MRI) scan shows granulomatous inflammatory swelling of the
sinus cavernous, which can reach the apex of the orbital cavity. The pain
and the eye muscle paresis usually disappear spontaneously, there is
however a tendency for the symptoms to reoccur. Administration of
glucocorticoids leads to pain reduction within 24 to 72 hours. Normalization of MRI scans typically takes 2 to 8 weeks. In the following, we
present a girl diagnosed with Tolosa Hunt syndrome and discuss the
differential diagnosis to other painful ophthalmoplegias. Case Report:
An 11-year-old girl first presented with an acute left sided abducens
paresis. Anamnesis revealed pain 5 days before in the area of the left
temple. Aside from the left-sided abducens paresis, discrete ptosis and
enophthalmus were also present. Complete blood count, inflammatory
parameters, cerebrospinal fluid (CSF) and MRI scan were without
pathological findings. The paresis and the pain resolved spontaneously
within 1 week. After 4 weeks, oculomotor nerve palsy and left-sided
temporal pain as well as pain over the left eyebrow appeared. CSF was
again unremarkable, whereas MRI scan showed an increase in volume of
the sinus cavernosus. Tolosa Hunt syndrome was diagnosed based on
the clinical findings and the MRI result. Therapy with methylprednisolone 1.4 mg/kg/d led to a significant pain relief within 24 hours.
Oculomotor nerve palsy discretely improved during the first week of
therapy. Conclusion: Tolosa Hunt syndrome is a rare disease, especially
in childhood. Diagnosis can only be made after excluding other causes of
painful ophthalmoplegia (tumors, vasculitis, infections, and vascular
malformations). Clinically, the symptoms can also resemble those of
ophthalmoplegic migraine. Repeated MRI scans may therefore be
necessary to detect signs of inflammation that often do not exist in
the initial stage. Consensus exists regarding Cortisone therapy, whereby
dosage and duration have not yet been clearly determined.
P076
New Diagnostic Opportunities with “NextGeneration-Sequencing”: Diagnosis of PNPLA2
gene Associated Lipid Storage Myopathy with
CK Elevation
Schwerin-Nagel A.1, Brunner-Krainz M.1, Kortschak A.1,
Haber E.1, Gruber-Sedlmayr U.1, Bittner R.2
1
Universitätsklinik für Kinder- und Jugendheilkunde, Graz,
Austria, 2Medical University of Vienna, Neuromuscular
Research Department, Wien, Austria
Introduction: With “next generation sequencing,” a new method is
available which offers efficient possibility of parallel sequencing up to
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Abstracts
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Munich, 17th to 19th September 2014
P077
Cognitive Control Processes in Primary
Dystonia: Effects of Deep Brain Stimulation
Smitka M.1, von der Hagen M.1, Storch A.2, Sobottka S.3,
Beste C.4
1
Universitätsklinikum “Carl Gustav Carus,” Technische
Universität Dresen, Abteilung für Neuropädiatrie, Dresden,
Germany, 2Technische Universität Dresden, Klinik und
Poliklinik für Neurologie, Dresden, Germany, 3Klinik und
Poliklinik für Neurochirurgie, Universitätsklinikum Carl G.
Carus, TU Dresden, Dresden, Germany, 4Klinik und
Poliklinik für Kinder- und Jugendpsychiatrie und P,
Kognitive Neurophysiologie, Dresden, Germany
Primary torsion dystonia (DYT1) can be caused by mutations in the
TOR1A gene (MIM MIM605204) gene. Little is known so far on the
(molecular) pathogenesis and protein function of DYT1. Neurochemical
analyses revealed decreased striatal dopamine in affected transgenic
mice. DYT1 usually begins in childhood or adolescence with progressive
involuntary posturing of the trunk, neck, or limbs. The most efficient
treatment is deep brain stimulation (DBS) of the globus pallidus
internus or thalamus. While the effects on motor functions are well
known, little is known about the effect of DYT1 and deep brain
stimulation in this disease on cognitive control processes related to
the inhibition of responses. Using cognitive neurophysiological techniques, we recorded event-related potential (ERPs) reflecting cognitive
subprocesses of response inhibition in a 13-year-old boy with a mutation in the DYT1 gene before DBS surgery and under deep brain
stimulation in comparison to a healthy control group. Disease manifested at the age of 9 and 12 years, the boy lost ambulation. The results
show that DYT1 comes along with deficits in response inhibition
processes; however, DBS ameliorated these cognitive control deficits.
Both, behavioral data and neurophysiological data showed that response inhibition processes becomes comparable to a normal level
under DBS in DYT1.
P078
only during speech. For this reason, speech is clearly impaired. Words
cannot be articulated; a consequence of involuntary movements of the
tongue, usually with curling of the tongue upward or downward. To date,
only six cases have been described in the literature. Patients and
Methods: Two women (age, 16 and 44 years) fell ill within 1 to 2 years
with SILD. The overall neurologic and clinical status indicated slight
right hemidystonia undiagnosed to date in the 16-year-old woman. The
44-year-old woman could reduce the tongue movements somewhat by
chewing gum. No such trick helped in the other patient. In both the
cases, there was upward curling of the tongue. Treatment and Results:
The electromyographic testing of the intrinsic tongue musculature
showed dense patterns of action potentials of motoric units. Attempted
treatment with L-dopa exhibited no effect in the 44-year-old woman.
Surprisingly in the young woman, there was a clear improvement in
speech under L-dopa such that a planned treatment with botulinum
toxin (BTX) could be abandoned. Her dystonia symptoms worsened
when she inadvertently forgot to take L-dopa. An electromyogramguided injection of 0.25 mL each BTX A (12.5 U Xeomino (R)) into the
muscles. Transversi linguae was performed in the 44-year-old woman.
For 4 years now, she has got along very well with the BTX treatment at
intervals of 6 to 8 weeks. Summary: Even with the rare disorder SILD, an
l-dopa test should always be performed. EMG-guided BTX treatment can
be an effective therapy; such a case has already been reported in the
literature.1
Reference
1 Ozen B, Gunal DI, Turkmen C, Agan K, Elmaci NT. Speech-induced
primary lingual dystonia: a rare focal dystonia. Neurol Sci. 2011;
32(1):155–157
P079
ATP2A2 Mutation as Cause for Morbus Darier,
Emotional Disturbances and Nighttime Seizures
in One Family
Stoffels J.1, von Czettritz G.1, Seeliger S.1
1
Kinderklinik St. Elisabeth Neuburg an der Donau, Neuburg,
Germany
We are reporting a 10-year-old female patient suffering from nighttime
seizures und emotional disturbances. The electroencephalography recording is showing interictual bifrontal slowing and bilateral frontal
spikes. The grandmother and her father had epilepsy until midtime
adulthood. Grandmother and mother are showing mood alterations.
The grandmother is suffering from morbus darier since puberty. Morbus
Darier also named dysceratosis follicularis is based on mutations of
adenosine triphosphate-dependent Ca2+-channel. This channel is found
in heart, skin, and also in the thalamus. It is part of an oscillatory triade
together with voltage-gated t-type Ca2+ channels and Ca2+ activated K+
channels. Lamotrigine therapy resulted in freedom from seizures. Mood
disturbances have been ameliorated. Conclusion: Familiar Morbus
Darier can be an etiological hint for the underlying cause of epilepsy
and mood disorder. It might be possible that lamotrigine therapy can be
a specific therapeutic approach for this specific disorder.
Primary Speech-Induced Lingual Dystonia: A
Rare Focal Dystonia: Two Further Cases of Illness
Stenner A.1, Reichel G.2
1
Paracelsusklinik, MVZ Neurologie, Zwickau, Germany,
2
Paracelsusklinik, Kompetenzzentrum für
Bewegungsstörungen, Zwickau, Germany
Introduction: Primary speech-induced lingual dystonia (SILD) occurs
very rarely. In this disorder, dystonic lingual movements are triggered
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
100 gens (> 2,000 exons). Case Report: We report the case of a 4-yearold boy presenting with primary tiptoeing and reduced walking distance (500 m). Pregnancy, birth, and development during the first year
with no abnormalities; walking with 16 months and primarily on tip
toes. Muscle reflexes reduced or absent, shortened hamstrings. Walking
on heels, standing, or hopping on one foot was not possible. Walking
upstairs reciprocal with balance problems, downstairs with holding;
stand-up from the squat with help of his arms, and running slowly.
Muscle strength of lower extremity reduced and of upper extremity was
normal. Creatine kinase between 1,724 U/I and 2,471U/l. Lactate dehydrogenase was 846 U/L, ASAT 84U/L, ALAT 98 U/L, lactate normal,
multiplex ligation-dependent probe amplification analyze negative
for dystrophine gen; acylcarnitine, amino acids in serum normal;
organic acids in urine normal. Echocardiography was normal. Muscle
biopsy: lipid storage vacuoles in muscle fibers; immunohistochemistry
was negative for muscle dystrophy associated proteins. Next generation
sequencing of PNPLA2 gene has homozygous mutation in exon 5.
Conclusion: With muscle biopsy, lipid storage myopathy was suspected.
Defects in carnitine cycle and fatty acid oxidation were excluded. The
definite diagnosis was found with “next generation sequencing”: a
PNPLA2-associated lipid storage myopathy. Beside myopathy diabetes
mellitus, hypertriglyceridemia, cardiomyopathy, and hepatomegaly or
steatosis hepatis can be found as further symptoms. In this case, precise
molecular diagnosis offers genetic counselling for the family and
appropriate follow-up for the patient.
S48
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Munich, 17th to 19th September 2014
P080
Therapy-Refractory Progressive Paraneoplastic
Sensorimotor Polyneuropathy in a Juvenile
Patient with Intracranial Sarcoma
Munich, 17th to 19th September 2014
Storch K.1, Smitka M.1, Hahn G.2, Lindner C.3, Friebel D.1,
Knöfler R.4, Suttorp M.4, von der Hagen M.1
1
Universitätsklinikum “Carl Gustav Carus,” Technische
Universität Dresden, Abteilung für Neuropädiatrie,
Dresden, Germany, 2Universitätsklinikum “Carl Gustav
Carus,” Technische Universität Dresden, Institut und
Poliklinik für radiologische Diagnostik, Dresden, Germany,
3
Universitätsklinikum “Carl Gustav Carus,” Technische
Universität Dresden, Klinik für Neurochirurgie, Dresden,
Germany, 4Universitätsklinikum “Carl Gustav Carus,”
Technische Universität Dresden, Klinik und Poliklinik für
Kinder- und Jugendmedizin, Dresden, Germany
Introduction: Paraneoplastic neurological syndromes are rare but can
affect any part of the peripheral nervous system (PNS) including motor
neurons, sensory ganglia, nerve roots, plexuses, cranial and peripheral
nerves, and neuromuscular junctions. Pathogenesis also varies from
direct infiltration by cancer cells, to treatment toxicity, to metabolic
derangement, cachexia, infections and paraneoplastic syndromes. Case
Report: We report the case of a 15-year-old male patient who presented
with a 4 weeks history of progressive gait instability and neuropathic
pain on excertion. Clinical neurological examination showed hyporeflexia of inferior extremities, ataxia, progressive neuropathic pain and
predominant distal muscle weakness. An elevated protein concentration
without pleocytosis was found in cerebrospinal fluid. Electrophysiological studies revealed a progressive lower extremities axonal neuropathy
predominant of the sensory nerves, a demyelinating neuropathy predominant of the motor nerves and a conduction block. The patient
received two courses of intravenous immunoglobulin (0.6 g/kg/d) 6 and
8 weeks after symptoms onset without any significant clinical change
and continuing progressive polyneuropathy. After 9 weeks of onset of
symptoms, a 3-day course of methylprednisolone (1,000 mg/d) was
given but the patient’s situation did not improve. Cranial MRI revealed
leptomenigeal enhancement including the cranial (V, VII, VIII, IX, X, and
bilateral) and spinal nerves, and cranial parenchyma lesions. Extensive
diagnostic for autoantibodies was not conclusive. Brain biopsy of the
cerebellar lesions revealed histologic finding of small blue round
malignant cells compatible with undifferentiated cerebral sarcoma.
The patient was treated with polychemotherapy and craniospinal
radiation according to the CWS guidance for NRSTS High Risk Group.
The tumor lesions decreased but the polyneuropathy-associated symptoms progressed, and 3 months after diagnosis, the patient was no
longer able to walk. Immunoadsorption is considered after the end of
polychemotherapy. Conclusion: Paraneoplastic neuropathy is rare in
childhood. This case report describes for the first time a therapy
refractory clinical course of a paraneoplastic sensorimotor polyneuropathy associated with isolated cerebral sarcoma. As there are presently no
established treatment guidelines based on larger cohorts or even
randomized controlled trials, therapeutic algorithms and decisions in
paraneoplastic neuropathies continue to remain a challenge.
P081
MOG-IgG-Positive Spinal Myelitis a Likely
Variant of Neuromyelitis Optica: Overcoming
Difficulties in Clinic, Diagnostic, and Therapy
Thiels C.1, Kleiter I.2, Rostásy K.3, Köhler C.1, Lücke T.1
1
Klinik für Kinder- und Jugendmedizin der RuhrUniversität Bochum, Neuropädiatrie mit Sozialpädiatrie,
Bochum, Germany, 2Ruhr Universität Bochum, St. JosefHosital, Neurologie, Bochum, Germany, 3Department of
Pediatrics I, Neuropediatrics, Medical University Innsbruck,
Innsbruck, Austria
Introduction: Neuromyelitis optica (NMO) is an inflammation demyelinating autoimmune disease; it is now known to be its own entity. NMO
now refers to a syndrome characterized by severe bilateral optic neuritis
associated with a transverse extensive myelitis, which spans more than
three consecutive vertebral segments. Furthermore, AQP4 antibody is a
specific autoantibody and targets aquaporin-4 water channel. It is
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
detected in 80% of adult NMO patients. Our report presents a patient
with relapsing severe longitudinal myelitis, AQP-4-seronegative, which
we would tend to class etiologically as an NMO variant. Case Report:
First and only child of nonconsanguin parents with a genetically
unclassified Keratitis-Ichthyosis-Deafness syndrome. Aged 9.5 years,
developing spinal ataxia, aggravating over a period of 14 days. Spinal
magnetic resonance imaging (MRI) increased signal throughout nearly
the whole spinal cord with enlarged, edematous central cord. Postcontrast no enhancement was observed. Somatosensory evoked potentials
(N. tibialis) were not reproducible. Comprehensive diagnostics (metabolic investigations, steroid sulfatase, phytanic acid, T- and B-cell
function, AQP-4-antibody, Biochip-mosaic, virology, and bacteriology)
remained inconspicuous apart from clearly elevated myelin oligodendrocyte glycoprotein (MOG) antibody as well as slightly elevated
cerebrospinal fluid albumin. After methylprednisolone (MP) for 3
days, the patient improved, but still ataxia gait. After 14 days, control
of spinal MRI revealed regression of radiological findings. No indication
for new lesions and normal brain MRI was seen. Within 2 months, the
boy presented with gait loss, spinal MRI showed progressive damage
with postcontrast enhancement. Because of deterioration in spite of
repeated MP therapy, intravenous immunoglobulin (IVIG) was established resulting in only slight improvement and eventually plasmapheresis was done. This again led to further slight amelioration. But 2
months later, he developed a posterior reversible encephalopathy
syndrome with seizures and arterial hypertension. In the course of
disease diaphragm, paralysis developed and it required a mask ventilation during night. On the basis of suspicions of an auto immunological
pathomechanism (MOG-antibodies permanently high) therapy with
corticosteroids, azathioprine, and IVIG was started. Improvement was
brought about a disconnection of mask ventilation, increasing agility of
legs but without gait capability. Summary: Severe MOG-antibodyassociated clinical picture with isolated longitudinal myelitis makes
an NMO-like disease likely. Therapy should be correspondingly
aggressive.
P082
Glatiramer Acetate As a Therapeutic Option in
Relapsing Optic Neuritis, MOG-, and NMO-IgGSeronegative
Thiels C.1, Kleiter I.2, Weigt-Usinger K.1, Salmen A.2, Köhler
C.1, Lücke T.1
1
Klinik für Kinder- und Jugendmedizin der RuhrUniversität Bochum, Neuropädiatrie, Bochum, Germany,
2
St-Josef Hospital, Ruhr Universität Bochum, Neurologische
Klinik, Bochum, Germany
Introduction: A relapsing optic neuritis (rON) in childhood requires an
immunomodulation therapy to avoid relapse(s). There is no established
and validated therapeutic approach. Experiences have predominantly
been made with azathioprine. Because of its side effects, therapeutic
alternatives are desirable. There are only a few reports on glatiramer
acetate (GLAT). This is a report on a female patient with unilateral rON,
MOG-, and NMO-IgG-seronegative on GLAT. A positive therapeutic
effect of GLAT can be assumed given the outcome in this patient. Case
Report: A female adolescent aged 12.5 years with painful and rapidly
increasing visual impairment (left side). Initially, conjunctivitis was
suggested, but subsequent deterioration led to diagnosis of papillitis,
indicating methyl prednisolone (MP) treatment. Visual function ameliorated under MP and deteriorated when corticosteroids were gradually reduced. Meanwhile, patient had developed a mild Cushing
syndrome. On first, presentation in our department for second opinion,
she showed visual function left eye: 0.67. The following parameters
were inconspicuous: brain and spinal magnetic resonance imaging,
cerebrospinal fluid, ENA- and ANA-Screen, MOG- and NMO-IgG-antibody. The positive effect of MP suggested an auto immunological
pathomechanism. The prolonged course of disease required an immunomodulatory therapy. We opted for GLAT due to its advantageous side
effects. Initially, this led to visual improvement, followed however by
drastic deterioration with complete unilateral visual loss after 4 weeks.
We performed a plasmapheresis which was well tolerated by the patient
and achieved a restitutio ad integrum. GLAT was continued. Relapses
occurred only in connection with noncompliance to GLAT injection over
Abstracts
S49
Munich, 17th to 19th September 2014
5, respectively 8 days. With MP over 3 days, visual function could be
regained twice. Summary: There is no established guideline for the
treatment of rON. The effect on our patient serves as a further example
for the potential of GLAT in the treatment of rON. The data however does
not (yet) allow a general recommendation of GLAT therapy.
P083
Fibrocartilaginous Embolism in Anterior Spinal
Artery Syndrome
Spinal cord infarction in childhood is extremely rare. Characteristics of
an anterior spinal artery syndrome are subacute pain with transition to
paraplegia and a dissociated paresthesia with concomitant vesicorectal
dysfunction. In 2013, we treated two patients with peracute nontraumatic paraplegia after the initial pain in the upper thoracic/cervical
spine. Patient 1, a 14-year-old boy, experienced a stinging pain in the
thoracic spine after minimal strain and rapidly developed a weakness. At
admission, he showed an incomplete paraplegia concentrating on the
right lower extremity and vivid muscle reflexes. Furthermore, he
displayed a reduced sensibility and a voiding dysfunction. The magnetic
resonance images (MRI) showed long distance signal alterations in the
cervical myelon (C2/3 and C5-7), which were considered as edema.
Extensive diagnostics including vascular, thrombophilic, cerebrospinal
fluid, and autoimmune parameters did not yield any etiologic risk
factors. After rehabilitation, the boy achieved major improvement of
function. Patient 2, a 15-year-old boy, suffered from weakness of the legs
while walking around. He reported a major pain in the neck the day
before without any trauma. He developed an incomplete tetraparesis
with paresthesia and voiding dysfunction within a few hours. The MRI
showed lesions with partially barrier dysfunction in the cervical myelon
(C3-C6), which were considered as spinal ischemia. In the axial sequences, T2w hyperintensities in the anterior myelon were visible, known as
“snake bite.” After rehabilitation, the patient regained almost complete
resolution of all functions. In both the patients, vascular disease (ischemia, bleeding, and vessel malformation), inflammatory disease (acute
myelitis transversa, multiple sclerosis, and neuroborreliosis), and spinal
tumors were excluded. On the basis of nontraumatic pain in the recent
past and otherwise unknown etiology, we suggest a fibrocartilaginous
embolus as the pathogenetic cause of a spinal ischemia. Hereby,
particles of an acute vertical disk herniation of the nucleus pulposus
material are mobilized under strain and are embolized through microlesions into the anterior spinal artery.
P084
Basal Ganglia Infarction in a 23-Year-Old Patient
with Duchenne Muscular Dystrophy: A Rare
Complication
Vietzke D.1, Della Marina A.1, Müntjes C.2, MöllerHartmann C.3, Schara U.1
1
Department of Pediatric Neurology, Developmental
Neurology and Social Pediatrics, University Hospital Essen,
Essen, Germany, 2Pediatric Cardiology, Department of
Pediatrics III, University Hospital Essen, Essen, Germany,
3
Institute for Diagnostic and Interventional Radiology and
Neuroradiology, University Hospital Essen, Essen, Germany
P085
Clinical Case Report: Manifestation of
Hereditary Neuralgic Amyotrophy in Childhood
Voges L.1, Stettner G.1, Weise D.1, Brockmann K.1, Gärtner J.1,
Henneke M.1
1
Klinik für Kinder- und Jugendmedizin, Neuropädiatrie,
Göttingen, Germany
Background: Neuralgic amyotrophy is marked by sudden onset of
severe pain in proximal upper limb and subsequent amyotrophy.
Idiopathic neuralgic amyotrophy (INA) can be distinguished from
hereditary neuralgic amyotrophy (HNA). HNA is commonly caused by
mutations in the SEPT9 gene and is inherited in an autosomal dominant
manner. The gene codes for a septin for which an influence on cellular
motility and polarity is assumed. To date, differences between INA and
HNA have been characterized in a cohort of mainly adult patients. The
clinical presentation of patients with INA and HNA is similar. However,
HNA shows a lower age of onset, a more frequent involvement of
peripheral nerves outside the brachial plexus, and a higher number of
recurrent episodes. Aim: This article aims for characterization of childhood onset HNA in a single patient by neuroradiologic, neurophysiologic, and genetic findings. Case Report: The index patient presented with
predominantly nocturnal pain in the upper left arm with reduced
elevation at age 6 years after an upper respiratory tract infection.
Clinical examination exhibited an incomplete paresis of deltoid, supraspinatus, and latissmus dorsi muscles and an atrophy of the deltoid
muscle. Magnetic resonance imaging showed a focal enhancement of
gadolinium along the brachial plexus. Motor neurography of the brachial plexus revealed a reduced nerve conduction velocity. Pain attacks
occurred recurrently over a month and were alleviated by ibuprofen.
The motor impairment continuously improved by means of physiotherapy as well as the muscle atrophy. At the age of 3 years, a similar episode
of illness appeared at the contralateral arm after a coxsackievirus
infection. Detailed family history did not yield any evidence for HNA
in other relatives. Because of the recurrent course of the disease with
early age of onset, HNA was suspected. Detection of a heterozygous
duplication beginning at exon 2 of the SEPT9 gene finally confirmed the
diagnosis. Genetic examination of the parents is ongoing. Conclusion: To
date, there are only few reports of childhood onset neuralgic amyotrophy. Molecular genetic testing regarding HNA should also be considered when family history is unremarkable, especially in patients with an
early age of onset and recurrent episodes of neuralgic amyotrophy.
Introduction: Duchenne muscular dystrophy is an X-linked inherited
disorder characterized by deletions, duplications, or point mutations in
the dystrophin gene, which is associated with a progressive generalized
muscle weakness, consecutive joint contractures, and increasing inactivity. The morbidity is often characterized by a progressive cardiomyopathy and heart failure, as well as a progressive restrictive ventilatory
defect with subsequent chronic respiratory insufficiency. However, a
cerebral infarction is a very rare complication of Duchenne patients, four
patients are currently described in the literature. Case Report: A 23year-old patient with a far progressed Duchenne muscular dystrophy
with acute apraxia showed a right-sided flaccid paralysis, aphasia, and a
consciousness disorder. Using cerebral magnetic resonance imaging and
angiography, it was possible to detect a left-sided basal ganglia infarc-
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
Toben J.1, Hasilik M.1, Weiss D.1, Denecke J.1
1
Pädiatrie/Neuropädiatrie, Universitätsklinikum Hamburg
Eppendorf, Hamburg, Germany
tion including an infarction of the insular cortex. The following day,
there was a spontaneous complete regression of the clinical symptoms,
particularly the right-sided paralysis. It was started a therapy with
acetylsalicylic acid for inhibition of platelet aggregation as a prophylaxis. Except for a slight protein S deficiency of 52% and a cardiomyopathy,
there were found no other risk factors for stroke. Summary: Particularly
in patients with Duchenne muscular dystrophy in very far progressed
stages of the disease, which are already largely immobile with multiple
joint contractures and generalized severe muscle weakness, the diagnosis of a cerebral insult is more difficult as a paralysis is not always
clearly identifiable. Therefore, it is important to consider in Duchenne
patients in case of acute neurological symptoms as a differential
diagnosis that a cerebral insult could occur with need of an immediate
initiation of a diagnostic imaging.
S50
Abstracts
Munich, 17th to 19th September 2014
P086
Tonic Seizures As a Prognostic Factor for
Seizure-Freedom and Development in
Myoclonic Astatic Epilepsy
Munich, 17th to 19th September 2014
von Spiczak S.1, Kleiss R.1, Vollrath O.2, Boor R.1, Muhle H.1,
Jacobs-Le Van J.3, Bast T.4, Wolff M.5, Kluger G.6, Steinbeisvon Stülpnagel C.6, Spiegler J.7, Reutlinger C.8, Steiner G.9,
Neubauer B.10, Møller R.11, Larsen J.11, Hjalgrim H.11,
Stephani U.1, Hedderich J.2, Helbig I.1
1
Universitätsklinikum Schleswig-Holstein, Campus Kiel,
Klinik für Neuropädiatrie, Kiel, Germany,
2
Universitätsklinikum Schleswig-Holstein, Campus Kiel,
Institut für Medizinische Informatik und Statistik, Kiel,
Germany, 3Universitätsklinikum Freiburg, Zentrum für
Kinder- und Jugendmedizin, Freiburg, Germany,
4
Epilepsiezentrum Kork, Kinderklinik, Kehl-Kork, Germany,
5
Universitäts-Klinik für Kinder- und Jugendmedizin,
Neuropädiatrie, Tübingen, Germany, 6Schön Klinik
Vogtareuth, Epilepsiezentrum für Kinder und Jugendliche,
Vogtareuth, Germany, 7Universitätsklinikum SchleswigHolstein, Campus Lübeck, Klinik für Kinder- und
Jugendmedizin, Lübeck, Germany, 8Helios Klinik
Geesthacht, Geesthacht, Germany, 9Imland Klinik
Rendsburg, Rendsburg, Germany, 10Universitätsklinikum
Giessen und Marburg, Zentrum für Kinderheilkunde und
Jugendmedizin, Giessen, Germany, 11Epilepsihospitalet
Filadelfia, Dianalund, Dänemark
Aim: Myoclonic astatic epilepsy (MAE) is a rare type of epilepsy
occurring in early childhood with a clinical spectrum from easy-to-treat
epilepsy to therapy-resistant epilepsy with severe developmental problems. The aim of this study was to identify clinical and genetic risk
factors determining the prognosis of MAE. Methods: Patients with MAE
were characterized with respect to the clinical course of the epilepsy.
The time from seizure manifestation to seizure freedom and the
developmental outcome were defined as primary outcome measures.
An explorative analysis of all clinical parameters was performed using
univariate statistics (log-rank test for “seizure freedom” and chi-square
test for “developmental outcome”) followed by a multivariate analysis
(Cox regression for “seizure freedom,” “ordinal regression for,” and
“developmental outcome”). Significance was defined as p < 0.05. The
gene SLC2A1, coding for the glucose transporter of the blood-brain
barrier, GLUT1, was investigated using Sanger sequencing. Results: A
total of 52 patients (40 males and 12 females) were included in the
analysis. The univariate analysis revealed several clinical parameters
which were significantly associated with the outcome measures. Within
the multivariate analysis, the outcome parameter “seizure freedom” was
negatively associated with the occurrence of “tonic seizures” (p < 0.001;
hazard ratio, 0.18; 95% confidence interval, 0.07-0.45), whereas the
“primary diagnosis of MAE” showed a positive association (p ¼ 0.001;
hazard ratio, 3.91; 95% confidence interval (CI) 1.8-8.51). For “developmental outcome,” significant prognostic factors were “primary developmental delay” (p ¼ 0.01), “tonic seizures” (p ¼ 0.03) and “MRI
abnormalities” (p ¼ 0.04). No mutations were identified in the SLC2A1
gene. Conclusion: Our study confirms previously published risk factors
for poor prognosis in MAE. Especially, the occurrence of tonic seizures
was found to be a negative prognostic factor for both seizure freedom
and developmental outcome. Additional investigations are needed to
decide whether these factors can be used to define different subtypes of
MAE and whether specific treatment regimens are needed. GLUT1
deficiency as the most frequent known genetic cause of MAE was absent
in our cohort.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
P087
A New SYNGAP1 Stop Mutation in a Patient with
Idiopathic Generalized Epilepsy Showing
Photosensitivity and Electroencephalography
Normalization after Eye Opening
von Stülpnagel-Steinbeis C.1, Funke C.2, Haberl C.3,
Hörtnagel K.2, Jüngling J.2, Weber Y.4, Berweck S.5,
Staudt M.6, Kluger G.6
1
Schön Klinik Vogtareuth, Neuropädiatrie, Vogtareuth,
Germany, 2CeGaT GmbH, Tübingen, Germany, 3Praxis für
Neuropädiatrie, Starnberg, Germany, 4Department for
Neurology and Epileptology, Hertie Institute for Clinical
Brain, Tübingen, Germany, 5Schön Klinik Vogtareuth,
Neuropädiatrie, Vogtareuth, Germany, 6Schön Klinik
Vogtareuth, Klinik für Neuropädiatrie und Neurologische
Rehabilitation, Epilepsiezentrum für Kinder und
Jugendliche Vogtareuth, Germany
Background: SYNGAP1, which encodes a RAS-GTPase-activating protein
that influences α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid receptor trafficking and excitatory synaptic transmission, is located
on the short arm of chromosome 6 (6p21.3). SYNGAP1 gene mutations
have been associated to autism spectrum disorders, delay of psychomotor development, acquired microcephaly, and several forms of idiopathic generalized epilepsy like Tassinari syndrome. Patient: This 15-yearold, mentally retarded girl developed drop attacks at the age of 3.25
years, later clonic and clonic-tonic, as well as myoclonic seizures. Two
seizures were associated with fever. The epilepsy was well-controlled by
valproic acid (VPA). The electroencephalography (EEG) was characterized by generalized spike-wave activity and photosensitivity; eye
opening lead to complete EEG normalization. MRI was normal, and
there were no dysmorphic signs. Genetic analysis revealed a mutation
(c.348C>A, p.Y116*), which is a de novo mutation in exon 4 of the
SYNGAP1 gene, in a heterozygous state. This mutation is predicted to
lead to a premature stop codon. Discussion: This is the first description
of a so far not reported de novo SYNGAP1 mutation in a patient with
generalized idiopathic epilepsy with only mild mental retardation and
slight speech impairment together with a special EEG phenomenon and
a good therapeutic response to VPA. This might help to further elucidate
the SYNGAP1 phenotype. The reported cases in the literature showed
mainly a good anticonvulsive effect of VPA and topiramate (TPM).
Therefore, mutations in SYNGAP1 should be considered when a patient
with generalized epilepsy, speech impairment, and nonsyndromic
mental retardation is presented. In these patients, VPA and TPM could
be first choice anticonvulsive drugs.
Pancreatitis under Therapy with Rufinamide
P088
von Stülpnagel-Steinbeis C.1, Stoffels J.2, Kluger G.1
1
Schön Klinik Vogtareuth, Neuropädiatrie, Vogtareuth,
Germany, 2Kinderklinik St. Elisabeth Neuburg an der
Donau, Neuburg, Germany
Background: Rufinamide (RUF) was granted orphan drug status in 2004
and it received approval for use in Europe in 2007 and by the US FDA in
2008 for the adjunctive treatment of seizures associated with LennoxGastaut syndrome (LGS) in children 4 years of age or older. RUF is
generally well tolerated with common adverse effects (AE) such as
somnolence, nausea, and vomiting being observed in up to 60% of
treated children. AE are usually mild and self-limited; they are more
frequently observed in titration phase than during maintenance. We
report a patient with a newly diagnosed pancreatitis under RUF. Patient:
We report a case of 5½-year-old patients with pharmacoresitant
symptomatic focal epilepsy after neonatal herpes encephalitis with
tonic seizures during night time, few drop attacks, and atypical dialeptic
seizures with mydriasis. In addition, to the existing valproic acid (VPA)
with a serum level of 75 mg/dL RUF was newly added over 2 weeks with
a dose of 23 mg/kg. Two weeks after the start of the RUF, the patient
complained of abdominal pain and loss of appetite. Laboratory investigations showed a lipase serum level of 1,577 U/L and the patient was
diagnosed a pancreatitis. The VPA level remained at 75 mg/dL. Therefore,
RUF was stopped and the abdominal pain was reversible, the lipase
serum level fell down to 121 U/L. The general condition of this patient
Abstracts
S51
Munich, 17th to 19th September 2014
P089
Recurrent Stroke in Two Children with Basilar
Artery Occlusion and the Effects of
Immunomodulatory Therapy
Walsh S.1, Smitka M.1, Hahn G.2, Brenner S.3, Berner R.4,
Gerber J.5, Knöfler R.4, Steinlin M.6, von der Hagen M.1
1
Child Neurology, Children's Hospital, Technical University,
Dresden, Germany, 2Department of Radiology, Technical
University, Dresden, Germany, 3Pediatric Intensive Care
Unit, Children’s Hospital, Technical University, Dresden,
Germany, 4Children's Hospital, Technical University,
Dresden, Germany, 5Neuroradiology, Department of
Radiology, Technical University, Dresden, Germany, 6Child
Neurology, Children’s University Hospital, Bern,
Switzerland
Only 10 to 30% of pediatric arterial ischemic strokes occur in the
posterior circulation. The etiology of basilar artery occlusion (BAO) is
often unknown. We report the clinical course of two unrelated 9-yearold boys (P1 and P2) with recurrent stroke due to BAO despite intensive
antithrombotic treatment. P1 presented with headache, vertigo, ataxia,
and aphasia. Brain magnetic resonance imaging (MRI) revealed a
thrombosis in the distal basilar artery and bilateral infarctions in the
cerebellum. He was anticoagulated with unfractionated heparin (UFH).
P1 recovered gradually and had a first recurrence 9 days after the initial
stroke, despite antiplatelet prophylactic treatment with acetylic acid
(ASA) and a second relapse 4 weeks later, despite prophylactic anticoagulation with low-molecular-weight heparin. During the second
relapse, MRI revealed an almost total BAO. P1 underwent immediate
local thrombolysis with recombinant tissue plasminogen activator and
mechanical thrombectomy with temporary stenting. P2 presented with
acute right hemiparesis, aphasia, paresis of the hypoglossal nerve, and
progressive somnolence. Brain MRI revealed irregular vessel walls with
suspicion of a thrombus in the basilaris artery and the right posterior
cerebral artery, leading to brain stem and cerebellar infarctions. He had
two relapses within 15 days while on full antithrombotic treatment
with ASA and UFH. In both the cases, extensive diagnostic work-up did
not reveal the etiology. Both the patients underwent anticoagulation
with UFH at therapeutical dose, followed by dual antiplatelet therapy
(ASA and clopidogrel) after their second stroke recurrence. Assuming a
cerebral vasculitis, both boys received 5 days of methylprednisolone
pulse therapy after their second relapse and continuous immunomodulatory therapy with mycophenolate mofetil (MMF) thereafter. P1 and
P2 remained symptom- and relapse-free for 17 and 5 months, respectively. P1 has mildly reduced fine motor skills, and P2 has a mild right
hemiparesis. BAO is rare in childhood, with recurrence prevalence of 4 to
13% and poor outcome in 50%. Imaging characteristics of the basilar
artery, relapses despite antithrombotic treatment alone, and response
to immunomodulatory therapy point to childhood primary cerebral
angiitis of the central nervous system in the two patients. Treatment
with methylprednisolone and MMF in addition to dual antiplatelet
therapy has thus far prevented further relapses and was associated
with a satisfactory neurological outcome.
P090
Epilepsy Surgery for Focal Epilepsies of
Inflammatory Origin: Expanded Spectrum of
Indications
Weber K.1, Pieper T.1, Kudernatsch M.2, Staudt M.1
1
Epilepsy Center for Children and Adolescents, Schoen Klinik
Vogtareuth, Germany, 2Clinic for Neurosurgery and
Epilepsy Surgery, Schoen Klinik Vogtareuth, Germany
Objective: Rasmussen encephalitis (RE) is an established indication for
hemispherotomy. Because of the often diffuse or multifocal pathogenesis in other focal epilepsies of inflammatory origin, these patients are
frequently not considered suitable for surgery. In addition to eight
patients with unilateral RE, we present nine patients with focal epilepsies of different inflammatory origins, in which the indication for
surgery could be elaborated. Method: Retrospective analysis of 17
patients with pharmacoresistant focal epilepsies of inflammatory genesis who underwent epilepsy surgery between 2002 and 2013 in
Vogtareuth. Patients: Group 1: unilateral RE: n ¼ 8 Group 2: different
inflammatory origins: n ¼ 9 • herpes simplex encephalitis (HSE): n ¼ 5 •
migratory sinusitis (MS): n ¼ 2 • (1' with abscess formation, 1' with
diffuse frontal purulent meningitis) • neonatal early summer meningoencephalitis (ESME): n ¼ 1 • chronic bilateral encephalitis (CBE),
suspected bilateral RE: n ¼ 1 Onset of epilepsy: 4.5 years (range, 0.514 years) Antiepileptic drugs taken before surgery: 7.8 (range, 3-16) Age
at surgery: 8.8 years (0.5-16 years after manifestation of the epilepsy)
Postoperative follow-up: 4 years (range, 0.5-11 years) Results: Operations: Group 1: 8of 8 hemispherotomy (HT) Group 2: 4 of 9 HT (2' HSE,
1' ESME, 1' CBE) • 3 of 9 resection/disconnection temporo-parietooccipital (3' HSE) • 2 of 9 lesionectomy/subtotal resection of the frontal
lobe (2' MS) Evaluation: Preoperative video-electroencephalography
(EEG) monitoring in all patients. Intraoperative electrocorticography
and—if needed—intraoperative monitoring (VEP and MEP) in the patients
with circumscribed resections. Electrophysiology and cMRI: 4' bilateral
EEG pathology (2' HSE, 1' ESME, 1' CBE), 4' bilateral cMRI pathology
(3' HSE and 1' CBE) Postoperative outcome (Engel classification):
Group 1: Engel 1a (seizure-free since surgery): n ¼ 8, 8 of 8 second p RE
Group 2: Engel 1a (seizure-free since surgery): • n ¼ 3 (2/5 HSE, 1/2 MS—
abscessing type) • Engel 3a (> 50% seizure reduction): • n ¼ 6 (3/5 HSE, 1/
2 MS—diffuse type), 1/1 CBE,1/1 ESME Conclusion: Focal epilepsies due
to RE have the best postoperative outcome. Bilateral pathologies revealed by cMRI and EEG are no absolute contraindications for epilepsy
surgery; the diagnostic process aims at identifying the leading epileptogenic zone. Also, in patients with multiregional lesion patterns, which
are typical for patients after HSE a very good postoperative outcome can
be achieved by epilepsy surgery (mainly extended lobectomies).
P091
Central Core Myopathy with Mutation of the
RYR1 Gene in Combination with Mutation of the
COL6A2 Gene and Severe Infantile Myoclonic
Epilepsy
Weisbrod T.1, Keimer R.1, Biskup S.2, Bornemann A.3, Riedel
J.4
1
Stauferklinikum, Neuropädiatrie, Mutlangen, Germany,
2
CeGaT GmbH, Tübingen, Germany, 3Universitätsklinikum,
Institut für Pathologie und Neuropathologie, Tübingen,
Germany, 4Stauferklinikum, Kinder- und Jugendmedizin,
Mutlangen, Germany
Children with central core myopathy (CCD) are diagnosed by the clinical
symptom of muscle hypotonia. Primarily, the diagnosis is made by muscle
biopsy. The disease is caused by mutation in the RYR1 gene. Dysfunction
of the ryanodine receptor results in dysregulation of calcium metabolism
in the sarcoplasmic reticulum of muscle cells. Our patient showed typical
symptoms of congenital myopathy and dislocation of the hip from birth.
The diagnosis of CCD was made by muscle biopsy and confirmed by a gene
test which showed mutation in the RYR1 gene. In addition, there was a
mutation in the COL6A2 gene, which may encode for congenital muscular
dystrophy type Ulrich. At the age of approximately 8 months, the child
developed the symptoms of severe infantile myoclonic epilepsy with
generalized irregular polyspikes in the electroencephalography (EEG).
Seizures could be reduced by treatment with various antiepileptic drugs.
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
Munich, 17th to 19th September 2014
was always good. Discussion: To our knowledge, this is the first report of
a pancreatitis under treatment with RUF. RUF is reported to be well
tolerated, but it is known that RUF levels can be modified by the
concomitant administration of other antiepileptic drugs. Especially,
VPA decreases the clearance of RUF (up to 70%) and consequently
induces a marked increase in plasma RUF levels. Our patient received
a combination of VPA and RUF, as the VPA therapy had been well
tolerated in the past and the serum level did not change under RUF
therapy, we hypothesize that RUF was responsible for the pancreatitis or
either the RUF add-on therapy increased the potential of VPA for
pancreatitis side effects. This is supported by the restitutio and integrum
after stopping RUF. To get to know possible side effects of orphan drugs
after market introduction, all side effects should be collected in a
database and regularly evaluated.
S52
Abstracts
Munich, 17th to 19th September 2014
However, by introducing valproate and zonisamide, the EEG almost
normalized and the convulsions stopped. In literature, there are no
data about the combination of the mutation in the RYR1 gene and severe
epilepsy. As the CCD is a dysfunction of the intracellular calcium channels,
it must be assumed that the epilepsy is probably caused by central
nervous system involvement of the channel dysfunction. This essential
aspect has to be taken into consideration when deciding on the appropriate antiepileptic drug choice.
Munich, 17th to 19th September 2014
P092
Pseudotumor Cerebri in Childhood: Usefulness
of Noninvasive Diagnostic Tools
1
1
1
1
1
Wernicke C. , Michel J. , Schütz M. , Kraus V. , Juenger H. ,
Steinborn M.2, Sadowski B.3, Burdach S.1, Makowski C.1
1
Kinderklinik und Poliklinik des Klinikums rechts der Isar
der TUM, Kinderklinik Schwabing, München, Germany,
2
Institut für Radiologie, Klinikum Schwabing, München,
Germany, 3Institut für Augenheilkunde, Klinikum
Schwabing, München, Germany
Pseudotumor cerebri (PTC) is a rare disease in children with a mostly
unknown etiology. Common symptoms are headaches, nausea and
vomiting, papilledema, impaired vision, and cranial nerve palsies.
However, 30% of the pediatric cases present without headaches, which
makes diagnosis more difficult.1 In children, PTC presents more often
only with palsy of the N. abducens and papilledema. Common risk
factors in adults as female sex and obesity do not seem as important in
children. Therefore, the diagnostic criteria by Dandy were modified for
prepubertal children by Ko and Liu.2 Here, we present the clinical course
of four pediatric cases with PTC and evaluate funduscopy and measurement of the optic nerve sheath diameter (ONSD) by transbulbar
sonography as diagnostic parameters for monitoring intracranial pressure (ICP) in children with PTC. Hereby, we aim to securely reduce the
frequency of necessary lumbar punctures and magnetic resonance
imaging for follow-up. Case 1: A 9-month-old male patient with recurrent vomiting and abducens nerve palsy, cerebrospinal fluid opening
pressure at diagnosis 49 cm H2O (the 90 percentile of the cerebrospinal
fluid opening pressure is 28 cm H2O3). Case 2: A 6-year-old male patient
with abducens nerve palsy on the right eye, cerebrospinal fluid opening
pressure at diagnosis > 30 cm H2O. Case 3: A 14-year-old male patient
with headaches, obesity, cerebrospinal fluid opening pressure at diagnosis 68 cm H2O. Case 4: An 11-year-old female patient with abducens
nerve palsy on the right eye, visual field loss and back pain, history of
therapy with somatotropine, cerebrospinal fluid opening pressure at
diagnosis 78 cm H2O, persistent visual field loss and optic nerve atrophy.
All patients presented with papilledema and an elevated ONSD at
diagnosis and in the follow-up, correlating with clinical presentation
and elevated cerebrospinal fluid opening pressure. We emphasize on
the necessity of an early diagnosis and close monitoring of the ICP as
one-third of the children with PTC without headaches suffer from
persistent impaired vision despite an appropriate therapy.4 We conclude that funduscopy and measurement of the ONSD represent feasible
and noninvasive methods for follow-up in pediatric patients with PTC.
References
1 Reeves GD, Doyle DA, Growth hormone treatment and pseudotumor
cerebri: coincidence or close relationship? J Pediatr Endocrinol
Metab 2002;15 (Suppl 2):723–730
Neuropediatrics 2014; 45 (Suppl 1): S1–S52
2 Ko MW, Liu GT. Pediatric idiopathic intracranial hypertension
(Pseudotumor cerebri). Horm Res Paediatr 2010;74:381–389
3 Avery RA, Shah SS, Licht DJ, Seiden JA, Reference range for cerebrospinal fluid opening pressure in children. N Engl J Med 2010;363
(9):891–893
4 Lim M, Kurian M, Penn A, Calver D, Lin J–P. Visual failure without
headache in idiopathic intracranial hypertension. Arch Dis Child
2005;90:206–210
P093
Glycine Receptor Antibodies in a Boy with Focal
Epilepsy and Episodic Behavioral Disorder
Würfel E.1, Bien C.2, Vincent A.3, Woodhall M.3,
Brockmann K.1
1
Universitätsmedizin Göttingen, Sozialpädiatrisches
Zentrum, Göttingen, Germany, 2Krankenhaus Mara,
Epilepsie-Zentrum Bethel, Bielefeld, Germany,
3
Neurosciences Group, Nuffield Department of Clinical
Neurosciences, University of Oxford, Oxford, United
Kingdom
A wide range of clinical presentations including neuromuscular
disorders and autoimmune encephalopathies is being recognized to
be associated with various autoantibodies against synaptic proteins.
Glycine receptor (GlyR) antibodies have so far been found predominantly in adult patients with phenotypes comprising progressive
encephalomyelitis with rigidity and myoclonus, stiff-person syndrome or hyperekplexia. Recent observations also suggest a relevance
of GlyR antibodies in epilepsies of unknown cause. We report a 4-yearold boy who presented with a 2‐year history of drug-resistant focal
epilepsy with unusual seizure semiology including temper tantrums,
headache, clumsiness, and intermittently impaired speech. Cranial
magnetic resonance imaging at 3.0 T was normal. Investigation of
cerebrospinal fluid (CSF) was normal for cell count, glucose, proteins,
oligoclonal bands, amino acids, neurotransmitters, and pterines. There
was no serologic evidence for a borrelia infection or celiac disease. At the
age of 4 years 5 months, screening for neuronal autoantibodies revealed
GlyR antibodies in serum, not in CSF, confirmed in two independent
laboratories with initial titers of 1:400 (live cells, GlyR α1 IgG, Prof.
Vincent, Oxford) and 1:500 (formalin fixed cells, GlyR A1b IgG, Bielefeld,
Prof. Bien). Further autoimmune IgG antibodies including NMDA receptor, AMPAR-1 and •2 receptor, GABAB receptor, VGKC-complex, generalized anxiety disorder, MAG, MOG, Aquaporin-4, and onconeuronal
antibodies were not found. Ultrasound of abdomen, testicles and lymph
nodes, chest X-ray, and tumor markers provided no evidence for a
neoplasm. Immunomodulatory treatment with steroids resulted in
rapid and complete resolution of symptoms. Five months after onset
of treatment, when the patient had been well for 3 months, GlyR
antibodies were still present in serum at 1:200 (Prof. Vincent, Oxford)
and 1:500 (Prof. Bien, Bielefeld). Our observation widens the spectrum
of clinical presentations associated with GlyR antibodies and emphasizes the potential relevance of neuronal autoantibodies in epilepsies of
unknown cause in children. As reported in previous cases, the serum
antibody is the main source of antibodies in these patients but may not,
by itself, be sufficient to cause the syndrome. Clinical disease depends on
access of the antibodies from the serum to the brain. We encourage the
routine investigation of neuronal antibodies in unclassified and therapy-refractory epilepsies and fluctuating psychopathological symptoms
in childhood.