HRVATSKO DRUŠTVO ZA DJEČJU NEUROLOGIJU
HRVATSKOG LIJEČNIČKOG ZBORA
SEKCIJA ZA BOLESTI METABOLIZMA HRVATSKOG
PEDIJATRIJSKOG DRUŠTVA HRVATSKOG
LIJEČNIČKOG ZBORA
ODJEL NEUROPEDIJATRIJE KLINIKE ZA DJEČJE
BOLESTI KLINIČKOG BOLNIČKOG CENTRA "SESTRE
MILOSRDNICE"
organiziraju
42. SIMPOZIJ HRVATSKOG DRUŠTVA ZA
DJEČJU NEUROLOGIJU
i
SASTANAK SEKCIJE ZA BOLESTI
METABOLIZMA HRVATSKOG
PEDIJATRIJSKOG DRUŠTVA
S MEĐUNARODNIM SUDJELOVANJEM
Hrvatski liječnički zbor, Šubićeva 9., Zagreb
Subota 7. prosinca 2013.
PROGRAM i ZBORNIK RADOVA / PROGRAM and BOOK OF ABSTRACTS
1
Drage kolegice i kolege, dragi gosti, dragi prijatelji
Ove godine obilježavamo 32. obljetnicu Hrvatskog društva za dječju neurologiju, koje je
osnovano u veljači 1981. godine, kao član Hrvatskog liječničkog zbora. Nakon osnivanja našeg
Društva, imamo redovite simpozije, jedan ili dva puta godišnje.
Čast nam je da se ove godine simpoziju Hrvatskog društva za dječju neurologiju
pridružila i Sekcija za bolesti metabolizma Hrvatskog pedijatrijskog društva.
U ime Organizacijskog odbora pozvamo Vas na 42. Simpozij Hrvatskog društva za
dječju neurologiju i na sastanak Sekcije za bolesti metabolizma Hrvatskog pedijatrijskog društva
koji se održava 7. prosinca 2013. u Velikoj predavaonici Hrvatskog liječničkog zbora, Šubićeva
9. u Zagrebu.
Sada, četvrti put od osnutka Društva 1981. godine, pripala je čast Odjelu
neuropedijatrije KBC Sestre milosrdnice da organizira Simpozij Hrvatskog društva za dječju
neurologiju, a ovaj put i sastanka Sekcija za bolesti metabolizma Hrvatskog pedijatrijskog
društva. Prvi put je Odsjek neuropedijatrije Klinike za pedijatriju u Kliničkoj bolnici Sestre
milosrdnice s prim. dr. Dragicom Rudar organizirao VII. Stručno-znanstveni sastanak Sekcije za
dječju neurologiju 1984. godine. Nadalje, u organizaciji predsjednice organizacijskog odbora
prof. dr. sc. Ljerke Cvitanović-Šojat sa suradnicima organiziranii su XVIII. Stručno-znanstveni
sastanak Društva za dječju neurologiju Zbora liječnika Hrvatske 1992. godine i 39. Simpozij
Hrvatskog društva za dječju neurologiju s međunarodnim sudjelovanjem 2010. godine. Ove
2013. godine pripala je čast organizacije i simpozija Hrvatskog društva za dječju neurologiju i
sastanka Sekcije za bolesti metabolizma Hrvatskog liječničkog zbora prof. dr. sc. Ljerki
Cvitanović-Šojat povodom njenog umirovljenja, nakon dugogodišnjeg uspješnog i predanog
rada na polju dječje neurologije, a u cilju nastavljanja njenog daljnjeg rada i vrijednih doprinosa
Hrvatskom društvu za dječju neurologiju, edukacije mlađih kolega, kao i za dobrobit naših malih
bolesnika.
Na ovom 42. Simpoziju Hrvatskog društva za dječju neurologiju i sastanku Sekcije za
bolesti metabolizma imamo 26. usmenih izlaganja, među kojima su i uvodna predavanja
kolegice i kolega iz Brusselsa, Heidelberga, Salzburga, Kranja, Ljubljane i Sarajeva, uz
predavanje članova obaju društava. Ova predavanja obuhvatila su glavne teme simpozija:
bolesti kretanja, cerebrovaskularne bolesti, genetiku, demijelinizirajuće bolesti, kao i slobodne
teme koje obuhvaćaju sva područja dječje neurologije i metabolizma. Uz ranije spomenute
kolege, uz neuropedijatre i pedijatre svoj rad i istraživanja prikazat će i kolege fizijatri i dječji
neurokirurg. Očekujemo rasprave, razmjene iskustava i spoznaja iz dječje neurologije,
metaboličkih bolesti i srodnih područja.
Predviđeno je radove sa ovog simpozija publicirati in extenso u posebnom redovnom
broju Paediatria Croatica tijekom 2014.
Vjerujemo da će ovaj Simpozij Hrvatskog društva za dječju neurologiju i Sastanak
Sekcije za bolesti metabolizma hrvatskog pedijatrijskog društva donijeti svima nama koristan i
ugodan završetak kalendarske godine 2013. i potaknuti nas u daljnjem radu i brizi za djecu s
neurološkim, genetskim i metaboličkim bolestima.
Pozivamo Vas na aktivno sudjelovanje na ovom simpoziju u svrhu kontinuiranog
napretka u radu s djecom oboljelom od neuroloških i metaboličkih bolesti u Hrvatskoj.
Predsjednica Hrvatskog društva za
Uži organizacijski odbor:
dječju neurologiju:
Prof. dr. sc. Ljerka Cvitanović-Šojat
Prof. dr. sc. Nina Barišić
Doc. dr. sc. Maša Malenica
Dr. Monika Kukuruzović
Predsjednik Sekcije za bolesti metabolizma
Dr. Tamara Žigman
Hrvatskog pedijatrijskog društva:
Bacc. med. techn. Kristina Kužmik
Prof. dr. sc. Ivo Barić
2
Letter of invitation
Dear colleagues, co-workers, guests and friends,
This year we celebrate the 32nd anniversary of the Croatian Pediatric Neurology Society,
a member of the Croatian Medical Association, founded in February 1981. To mark this
occasion we organize a joint meeting with the Section for metabolic diseases of the Croatian
Pediatric Society.
It is with great pleasure that we invite you to the 42 nd Symposium of the Croatian
Pediatric Neurology Society to be held on 7 th December 2013, at the Croatian Medical
Association in Zagreb, Šubićeva Street 9, as a joint meeting with the Section for metabolic
diseases of the Croatian Pediatric Society. Although it is only the 32 nd anniversary of our
Society, we are holding the 42nd Symposium because we used to meet more than once a year.
For the fourth time, since the founding of our Society, the Department of Child
Neurology of the University Clinical Center Sestre milosrdnice has the honor to organize the
Symposium of the Croatian Pediatric Neurology Society. In 1984, the 7 th Symposium was also
organized by the same Department and it was presided by Prim. Dragica Rudar MD; in 1992,
the 13th, and in 2010, 39th Symposia were organized by Prof. Ljerka Cvitanović-Šojat MD, PhD
with her co-workers.
This year, Prof. Ljerka Cvitanović-Šojat MD, PhD, who is retiring after many years of
particularly successful and dedicated work in the field of child neurology, has the honor to
organize the joint Meeting od the Croatian Pediatric Neurology Society and the Section for
metabolic diseases of the Croatian Pediatric Society. It is our hope that she will continue her
work and active contribution to the Croatian Pediatric Neurology Society, as well as the
education of younger colleagues for the benefit of our patients.
The scientific program of the 42 nd Symposium of the Croatian Pediatric Neurology
Society and the Meeting of the Section for metabolic diseases of the Croatian Pediatric
Society includes 26 lectures. Plenary sessions will be presented by colleagues from Brussels
(Belgium), Heidelberg (Germany), Salzburg (Austria), Kranj and Ljubljana (Slovenia), and
Sarajevo (Bosnia and Herzegovina). Plenary sessions, lectures, case reports, video and short
communications will be presented by members of both societies. The main topics of the 42 nd
Symposium are movement disorders, cerebrovascular diseases, genetics, demyelinating
disease, as well as other topics that cover all of the child neurology and inherited metabolic
diseases.
In 2014, we plan to publish in extenso the presentations from the 42nd Symposium in the
regular issue of the journal Paediatrica Croatica.
We believe that we will all greatly benefit from the 42 nd Symposium and we hope that all
our guests will enjoy their stay in Zagreb. Finally, at this year's end, we would also like all
participants to take home pleasant memories as well useful knowledge that will inspire them
and provide further motivation for work with children suffering from neurological, genetic and
metabolic diseases.
President of the Croatian Child
Local Organizing Committee:
Neurology Society:
Prof. dr. sc. Ljerka Cvitanović-Šojat
Prof. dr. sc. Nina Barišić
Doc. dr. sc. Maša Malenica
Dr. Monika Kukuruzović
President of the Section for metabolic
Dr. Tamara Žigman
diseases of the Croatian Pediatric Society:
Bacc. med. techn. Kristina Kužmik
Prof. dr. sc. Ivo Barić
3
ZNANSTVENI ODBOR / SCIENTIFIC COMMITTEE
Nina Barišić, Ivo Barić, Ljerka Cvitanović-Šojat, Sanja Delin, Vlasta Đuranović,
Dubravka Fajdetić, Romana Gjergja Juraski, Krasanka Hafner, Maja Jurin,
Matilda Kovač Šižgorić, Radenka Kuzmanić Šamija, Ivan Lehman, Vlatka
Mejaški-Bošnjak, Marija Meštrović, Dolores Petrović, Ljiljana PopovićMiočinović, Igor Prpić, Zlatko Sabol, Antun Sasso
POČASNI ODBOR / HONORARY COMMITTEE
Zdravka Bernić (Zagreb), Vera Durrigl (Zagreb), Marija Frleta (Split), Mladen Križ
(Rijeka), Anamaria Hlača Mikloušić (Zagreb), Martin Mikecin (Zadar), Branka Marušić
Della Marina (Zagreb), Ela Paučić Kirinčić (Rijeka), Duško Mardešić (Zagreb), Ognjen
Mladinov (Pula), Ines Rakvin (Zadar), Biserka Rešić (Split), Kate Rogulj (Dubrovnik),
Dragica Rudar (Zagreb), Eugenio Stoini (Šibenik), Štefica Sremić (Zagreb), Drago
Škarpa (Zagreb)
ORGANIZACIJSKI ODBOR / ORGANIZING COMMITTEE
Maša Malenica, Monika Kukuruzović, Tamara Žigman, Maja Crnkovič, Barbara
Perše, Matej Katavić, Maja Crnković, Kristina Kužnik, Snježana Stanić, Ružica
Begić, Blaženka Balaško, Mirjana Koprivnjak, Ivo Barić, Danijela Petković
Ramadža, Branka Bunoza, Petra Grđan
PREDSJEDNICA ORGANIZACIJSKOG ODBORA / PRESIDENT
OF THE ORGANIZING COMMITTEE
Ljerka Cvitanović-Šojat
OBAVIJESTI / INFORMATIONS
SLUŽBENI JEZIK: hrvatski i engleski / THE OFFICIAL LANGUAGE OF THE CONGRESS:
Croatian and English.
KOTIZACIJA / CONGRESS FEE
400 kuna za liječnike specijaliste; 150 kuna za specijalizante, stažiste, znanstvene
novake i medicinske sestre; besplatan ulaz za umirovljenike i studente
Kotizacija se uplaćuje na račun Hrvatskog društva za dječju neurologiju, HLZ, Šubićeva 9.,
Zagreb.
Broj IBANa HLZ: HR7423600001101214818, poziv na broj 268-36,
OIB 60192951611, svrha "KOTIZACIJA ZA 42. SIMPOZIJ"
Potrebno je pokazati dokaz o uplati kod registracije.
Simpozij će biti bodovan prema pravilima HLK.
ZA SVE OBAVIJESTI U SVEZI SIMPOZIJA MOŽETE SE OBRATITI / FOR INFORMATION:
Prof. dr. sc. Ljerka Cvitanović-Šojat: Mob 0981751431, e-mail: [email protected]; Doc. dr. sc. Maša Malenica: Mob 098800390, e-mail: [email protected]
Dr. Monika Kukuruzović: Mob 0915409058, e-mail: [email protected]
Dr. Tamara Žigman: Mob 0959063293, e-mail: [email protected]
Kristina Kužnik bacc med. tech: Mob 098385617, e-mail: [email protected]
4
PROGRAM 42. Simpozija HDDN i Sastanka Sekcije za bolesti metabolizma HPD /
PROGRAM of the 42nd Symposium of the Croatian Pediatric Neurology Society
and the Meeting of the Section for metabolic diseases of the Croatian Pediatric
Society
Subota, 7. prosinca 2013. /Saturday the 7 December 2013
08.00 – 08.40
Prijava sudionika / Registration of Participants
08.40 - 08.50
Otvaranje Simpozija i Sastanka / Opening of the Symposium and the
Meeting: N. Barišić, I. Barić, Lj. Cvitanović-Šojat, M. Malenica
Muzička točka / Musical intermezzo: Dubravko Lapaine - didgeridoo
08.50 – 09.00
Radno predsjedništvo /Chairs: N. Barišić, I. Barić
09.00 – 09.25
Linda De Meirleir (Brussels): Metabolic diseases mimicking cerebral
palsy or intellectual disability / Metaboličke bolesti koje oponašaju
cerebralnu paralizu ili intelektualno odstupanje
09.25 – 09.50
Nenad Blau (Heidelberg): The lumbar puncture as a tool in the
diagnosis of pediatric neurotransmitter disorders / Lumbalna
punkcija u dijagnostici poremećaja metabolizma neurotransmitera
kod djece
09.50 – 10.15
Wolfgang Sperl (Salzburg): Mitochondrial diseases with disturbances
in the ATP-synthesis – probably underdiagnosed / Mitohondrijske
bolesti s poremećajem u ATP sintezi – vjerojatno premalo
dijagnosticirane
10.15 – 10,40
Johannes Mayr (Salzburg): Defects in cofactor metabolism causing
mitochondrial diseases / Mitohondrijske bolesti uzrokovane
poremećajima u metabolizmu kofaktora
10,40 – 11,00
Ivo Barić (Zagreb): Inherited disorders of methylation / Nasljedni
poremećaji metilacije
Predstavljanje projekta/ Presentation of the project “ Inherited
NeuroMetabolic Diseases Information Network (InNerMed)”
11.00. – 11.20
Odmor / Break
Radno predsjedništvo / Chairs: Lj. Cvitanović-Šojat, V. Mejaški-Bošnjak
11.20 – 11.40
Milivoj Veličković (Kranj): Definition of alternative medicine /
Značenje alternativne medicine
11.40 – 12.00
Igor Ravnik (Ljubljana): Comprehensive management of severe
epilepsies in countries with limited resources: the case of small
populations / Sveobuhvatan pristup tvrdokorne epilepsije u
zemljama sa ograničenim mogućnostima: slučaj malih populacija
12.00 – 12.20
Smail Zubčević (Sarajevo): Neurodevelopmental outcome following
therapeutic hypothermia for perinatal asphyxia / Ishod razvoja kod
djece s perinatalnom asfiksijom nakon primjene hipotermije
12.20 – 12.40
Nina Barišić (Zagreb): Autoimune encefalopatije u djece /
Autoimmune encephalopathies in children
12.40 – 13.00
Ljerka Cvitanović-Šojat (Zagreb): Klinička slika i molekularna
analiza u braće s bolešću Niemann Pick tip C / Clinical presentation
and molecular analyses in siblings with Niemann Pick type C disease
13.00 – 13.45
Odmor / Break
Radno predsjedništvo / Chairs: B. Rešić, A. Sasso
13.45 – 14.00
Vlasta Đuranović (Zagreb): Progresivna okluzivna cerebralna
arteriopatija u djece / Progressive occlusive cerebral arteriopathy in
children
14.00 – 14.15
Matilda Kovač-Šišgorić (Zagreb): MASA syndrom - prikaz slučaja
5
14.15 – 14.30
14.30 – 14.45
14.45 – 15,00
15.00 – 15.15
dvoje braće blizanaca / MASA syndrome - report of a two twin
brothers
Radenka Kuzmanić Šamija (Split): Poremećaji kretanja kao simptom
paraneoplastičnih i autoimunih procesa / Movement disorders as a
symptom of paraneoplastic and autoimmune processes
Igor Prpić (Rijeka): Indikacije za slikovne pretrage tijekom
zbrinjavanja svakodnevnih kroničnih glavobolja kod djece /
Neuroimaging indications in management of chronic daily headache
in children
Romana Gjergja Juraški (Zagreb): Poremećaji spavanja u djece s
kromosomopatijama, genskim poremećajima i nasljednim
sindromskim obrascima / Sleep disturbances in children with
chromosomopathy, genopathy or hereditary syndromic pattern
Maša Malenica (Zagreb): Različite kliničke prezentacije iste mutacije
– Friedreichova ataksija / Identical mutation associated with distinct
clinical phenotypes of Friedreich's ataxia
Radno predsjedništvo / Chairs: Lj. Popović Miočinović, O. Mladinov
15.15 – 15.30
Dunja Čokolić-Petrović (Osijek): Nasljedna trombofilija kao rizični
faktor za nastanak moždanog udara u novorođenačkoj dobi /
Hereditary thrombophilia as a risk factor for stroke in newborns
15.30 – 15.45
Miroslav Gjurašin (Zagreb): Zbrinjavanje vaskularnih malformacija
mozga u djece / Management options of pediatric cerebral vascular
malformations
15.45 – 16.00
Ljiljana Popović-Miočinović (Zagreb): Migrena i epilepsija u obitelji
djece s cerebralnom paralizom / Migraine and epilepsy in a family
with children suffering from cerebral palsy
16.00 – 16.15
Karolina Župetić (Zagreb): Motivacija cerebralno paraliziranog
djeteta za terapiju / Motivation for therapy in children with cerebral
palsy for therapy
16.15 – 16.30
Odmor / Break
KRATKA PRIOPĆENJA od 5 min. / SHORT COMMUNICATIONS 5 min duration
Radno predsjedništvo / Chairs: M. Malenica, I. Lehman, D. Petković Ramadža
16.30 – 17.20
Andrea Šimić Klarić (Požega): Cerebralna paraliza i pridružena
neurorazvojna odstupanja u djece s kortikalnom disgenezom
/ Cerebral palsy and neurodevelopmental disorders associated
with cortical dysgenesis
Miroslav Gjurašin (Zagreb): Tumori lubanje u djece: prepoznavanje
i liječenje / Skull bone tumors in children: recognition and treatment
Katarina Bošnjak Nađ (Zagreb): Elektrofiziologija vida kod djece /
Electrophysiology of vision in children
Maja Jurin (Zagreb): Operabilni i neoperabilni slučajevi
farmakorezistentne epilepsije / Operable and inoperable cases of
drug resistant epilepsy
Sanja Delin (Zadar): Kongenitalna miotonička distrofija – prikaz
pacijenta / Congenital myotonyc dystrophy – case report
Danijela Petković Ramadža (Zagreb): Neuronopatski oblici
Gaucherove bolesti – izazovi u dijagnostici i liječenju /
Neuronopathic types of Gaucher disease-diagnostic and
therapeutic challenges
6
17.20 – 17.25
17.25 – 17.30
17.30 – 18.00
Godišnja nagrada Sekcije za bolesti metabolizma HPD / Annual
award of the Section for metabolic diseases of the Croatian Pediatric
Society
Zatvaranje 42. Simpozija HDDN i Sekcije za bolesti metabolizma
HPD /Closing remarks
Skupština HDDN / General Assembly of the Croatian Pediatric
Neurology Society
7
SAŽECI / ABSTRACTS
Linda De Meirleir
METABOLIC DISEASES MIMICKING CEREBRAL PALSY OR INTELLECTUAL
DISABILITY
Kinderneurologie en metabole ziekten, Universitair Ziekenhuis Brussel, Laarbeeklaan
101, 1090 Brussels, Belgium. E-mail: [email protected]
Metabolic diseases can present in a number of different ways. Some are diagnosed
after neonatal screening, other present with an acute encephalopathy associated with
biochemical disturbances such as acidosis, hypoglycaemia or hyperammonia. Other
metabolic diseases will have with a more chronic presentation, including developmental
delay, epilepsy and regression.
Associated neurological signs and symptoms such as extra neurological
manifestations, psychiatric signs, autistic traits, cerebellar dysfunction and dysmorphic
traits can lead to a clue for further specific investigation. Before the age of 5 year we
can speak of developmental delay, after that it is defined as mental retardation (MR) or
cognitive impairment. Assessment requires a multidisciplinary approach with extensive
family history, general physical and neurological examination, including vision and
hearing. With the use of the microarray and in some cases whole exome sequencing,
genetic tests sometimes precede the metabolic work-up.
In absence of dysmorphism basic blood tests can be recommended including T3,
creatine metabolites and urinary GAGS, purines and pyrimidines. The X-linked
creatine transporter defect for example can lead to mild to severe MR, associated with
expressive speech delay and autistic-like behaviour. MCT8 is another X-linked disorder
associating severe mental retardation, with delay in myelination, where high T3 is the
marker of this disease. Urinary organic acid analysis can lead to specific diagnosis
such as 4-OH butyric aciduria or L-2-OHglutaric aciduria. In the group of the
mucopolyssacharidoses especially Sanfillipo A and B can present with variable
behavioural disturbances and cognitive decline without clear somatic changes. The
same is true for alpha and beta mannosidosis, being picked up by urinary
oligosaccharides analysis. The expanding group of congenital disorders of CDG are
often associated with mental retardation, some also with specific MRI abnormalities
such as cerebellar atrophy. Many other metabolic disorders will present wit cognitive
impairment or behavioural changes and might lead to specific diagnosis such as
neuronal ceroid lipofuscinosis, Niemann Pick C, X-adrenoleukodystrophy, or
cerebrotendinous xanthomatosis and early diagnosis lead to a better outcome with the
appropriate treatment.
In the group of PDH-E1alpha, girls can present wit a static encephalopathy or West
syndrome, boys can have a slowly progressive Leigh’s disease. So think always also
metabolic.
8
Nenad Blau
THE LUMBAR PUNCTURE AS A TOOL IN THE DIAGNOSIS OF PEDIATRIC
NEUROTRANSMITTER DISORDERS
Senior Consultant in Biochemical Genetics, Division of Inborn Metabolic Diseases
University Children's Hospital, Department of General Pediatrics, Im Neuenheimer
Feld 430, Heidelberg, Germany and Division of Metabolism, University Children's
Hospital, Zürich, Switzerland
Neurotransmitters are endogenous compounds that transmit signals from a neuron to a
target cell across a synapse. Some neurotransmitters are commonly described as
"excitatory" or "inhibitory". Excitatory neurotransmitters (e.g. epinephrine,
norepinephrine, dopamine) and their receptors increase the neuron's internal electrical
activity and excitability. This increases the likelihood that a neuron will relay an
incoming signal. In contrast, inhibitory neurotransmitters (e.g. serotonin, GABA) and
their receptors reduce neuronal excitability and increase the likelihood that an incoming
signal will be terminated.
Pediatric neurotransmitter disorders (PND) refer to a constellation of neurometabolic
syndromes attributable to disturbances of neurotransmitter synthesis, degradation, or
transport. This lecture covers aspects of disorders of biogenic monoamines.
Monoamine deficiencies represent defects in synthesis or transport of dopamine,
norepinephrine, epinephrine and serotonin or in availability of tetrahydrobiopterin
(BH4), an important cofactor for monoamine synthesis. A significant proportion of
these disorders will not manifest peripheral hyperphenyalaninemia and require CSF
neurotransmitter metabolite assay for diagnosis. These include Segawa doparesponsive dystonia and enzymatic deficiencies of aromatic amino acid decarboxylase,
tyrosine hydroxylase, and sepiapterin reductase (SR). The first, autosomal dominantly
inherited GTP cyclohydrolase (GTPCH) deficiency has a satisfying response to L-dopa
therapy at any age with benefits maintained over time. The others have more severe
and treatment-refractory phenotypes, typically with manifestations well beyond
movement disorders. Many of these patients are initially misdiagnosed with cerebral
palsy. Disorders detectable through newborn screening for PKU by elevated blood
phenylalanine are autosomal-recessively inherited deficiencies of GTPCH,
dihydropteridine reductase (DHPR), and 6-pyruvoyl-tetrahydropterin synthase (PTPS).
The latter is the most prevalent and heterogeneous but typically has infantile onset with
extrapyramidal as well as bulbar, hypothalamic, limbic, and epileptic manifestations.
There are therapeutic roles for neurotransmitter supplementation and dopaminergic
agonists. Basal ganglia calcifications in DHPR deficiency are reversible with folinic
acid. Deficiencies of monoamine degradation lead to cognitive, behavioral, and
autonomic disorders.
Careful neurological examination and extensive CSF investigations are essential to
detect PND and to enable early pharmacological intervention to improve neurological
outcome.
Wolfgang Sperl, Johannes Mayr
9
MITOCHONDRIAL DISEASES WITH DISTURBANCES IN THE ATP-SYNTHESIS –
PROBABLY UNDERDIAGNOSED
Department of Pediatrics, Paracelsus Medical University (PMU), Salzburger
Landeskliniken (SALK), Müllner Hauptstraße 48, A-5020 Salzburg, Austria
Tel.: 0043-662-4482-2600; Fax : 0043-662-4482-2604; E-Mail: [email protected]
http://www.mitocenter.org
The synthesis of ATP in mitochondria is performed by the F 1FO ATP synthase but also
involves the adenine nucleotide translocator (ANT) and the mitochondrial phosphate
carrier (PiC). Mitochondrial DNA mutations of ATP6 and ATP8 are the most commonly
known diseases with the classical NARP and MILS phenotype. Recently also nuclear
well as TMEM70 mutations, an assembly factor of ATP synthase, with
encephalocardiomyopathy and 3-methylglutaconic aciduria (3-MGA). Other
disturbances of ATP synthesis are defects of ANT with the recently elucidated Sengers
syndrome due to acylglycerol kinase (AGK) deficiency and the defects of the
phosphate carrier with so far two families described.
The gold standard for the diagnostics of ATP synthesis defects is the investigation of
intact mitochondria from fresh samples, since the mitochondrial membrane potential is
necessary for its activity. Other methods like measurement of the oligomycin sensitive
ATPase and western blotting can be helpful but are not conclusive in all cases. In many
laboratories, none of these investigations are performed routinely.
The clinical presentation is heterogeneous but even in the classical NARP/MILS
mutations neurological involvement can be mild with predominance of cardiac
symptoms. TMEM70 deficiency is characteristic in many patients but also milder
phenotypes have been found. Sengers syndrome usually is characterized by bilateral
cataracts, CMP and lactic acidosis, mild forms with just cataracts also exist. In the few
known families with the PiC deficiency symptoms range from early severe lethal to
adult chronic forms. Remarkably in all types of defects of ATP synthesis
cardiomyopathy is highly prevalent.
From the experience of patients diagnosed in our centre many children with clear lactic
acidosis highly suspicious for a mitochondrial disorder have to be re-evaluated and can
be easily missed if the diagnostic workup is incomplete.
Johannes Mayr, Wolfgang Sperl
DEFECTS IN COFACTOR METABOLISM CAUSING MITOCHONDRIAL DISEASES
Department of Pediatrics, Paracelsus Medical University (PMU), Salzburger
Landeskliniken (SALK), Müllner Hauptstraße 48, A-5020 Salzburg, Austria
[email protected]; http://www.mitocenter.org
Cofactors are a group of small substances necessary for numerous cellular reactions.
Many enzymes of the mitochondrial energy metabolism depend on cofactors. Since the
oxidative energy production is essential for most tissues a manifestation of cofactor
defects as mitochondrial diseases is quite likely. Up to date defects in at least 33
different genes in the synthesis and transport of cofactors have been reported that
manifest clinically as disorders in the mitochondrial energy metabolism. The affected
cofactors include thiamine, lipoic acid, iron-sulphur clusters, heme, biotin, coenzyme A,
10
and coenzyme Q. The diagnostics of these disorders can either be made clinically, by
metabolite investigation, by measurement of affected pathways or by determining the
cofactor concentrations. In some cases the diagnostics is complicated due to tissue
specific affection or manifestation in specific organelles. For the identification of some
of these disorders only the functional investigation of intact mitochondria is informative.
In contrast to most other disorders of the mitochondrial energy metabolism, some of
these cofactor defects turned out to be treatable, e.g. defects in the biotin and
coenzyme Q metabolism and some disorders of the thiamine metabolism. Hence it is
crucial to early recognise and treat these disorders in order to prevent severe
symptoms.
Ivo Barić
INHERITED DISORDERS OF METHYLATION
Department of Pediatrics, University Hospital Center and School of Medicine, Zagreb,
Croatia, [email protected]
Methylation is a process necessary for countless molecules to work properly. It
happens by the transfer of methyl group from methionine via adenosylmethionine to
numerous acceptors of very variable function. This transfer or methyl groups or
transmethylation occurs in all mammalian cells reflecting its imprtance. The large list of
acceptors of methyl groups transferred by numerous methyltransferases includes
important molecules such as DNA, RNA, lipids, proteins, amino acids,
neurotransmitters, guanidinoacetate, etc. Therefore, it is not surprising that the
disorders which disturb transmethylation affect numerous tissues and organs. Sadenosylhomocysteine, which is the common product of all reactions catalyzed by
mentioned methyltransferases is also a potent inhibitor of these reactions. Therefore,
every influence which changes the concentration of S-adenosylhomocysteine and/or
ratio S-adenosylmethionine/S-adenosylhomocysteine can adversely affect methylation
in humans. Among these, inherited metabolic disorders of this metabolic pathway (from
methionine to homocysteine) have particular potential. In the last decade, important
new information about this pathway has been gained. Three novel disorders have been
discoveredglycine-N-methyltransferase
deficiency,
S-adenosylhomocysteine
hydrolase deficiency and adenosine kinase deficiency. The fourth disorder in this
pathway, methionine adenosyltransferase deficiency has been increasingly detected,
thanks to the expansion of newborn screening program. Getting knowledge on all these
disorders has made possible to learn about their pathogenesis and about importance of
methylation for organs which are affected in these disorders (brain, muscle, liver), but
also to get general insight into the crucial biological processes such as methylation,
transsulfuration or carcinogenesis in mammals, pathogenesis of numerous pathological
conditions, in particular those associated with hyperhomocysteinemia, action and
possible toxicity of some drugs or consequences of nutritional variations. From the
clinical viewpoint, in order to detect currently underdiagnosed methylation disorders, at
least methionine and later, in the case of hypermethioninemia, S-adenosylmethionine
and S-adenosylhomocysteine should be measured in all unexplained diseases
affecting brain, muscle and/or liver.
Mario Ćuk, Lidija Paležac, Nina Barišić, Ivan Lehman, Smiljak Vikić-Topić, Ivo Barić
11
InNerMeD – Inherited NeuroMetabolic Diseases Information Network
Department of Pediatrics, University Hospital Center and School of Medicine Zagreb,
Croatia
InNerMeD Information Network is an European research network funded by the
Directorate-General for Health and Consumers within the Second Health Programme
of the European Commission (Grant Agreement no. 201212121 - Collaborative
Project). InNerMeD is the first European Network on inherited neurometabolic diseases
(iNMDs) with the aim to create a multimedial network of information targeted on
research, diagnosis and treatment of iNMDs based on the collection and exchange of
validated information among scientific communities, health professionals, patients,
patient associations and all relevant stakeholders. InNerMeD project coordinator is
Brains for Brain Foundation (Italy), and InNerMeD partners are Gianni Benzi,
Pharmacological Reserach Foundation (Italy), Region Hovedstaden, Department of
Clinical Genetics (Denmark), Johannes Gutenberg University of Mainz (Germany),
University of Zagreb, School of Medicine, (Croatia), Hospital Sant Joan de Deu (Spain)
including collaborating partners wordwide. Since iNMDs represent an important group
of Rare Diseases, the network will increase the current knowledge on iNMDs, speed up
the timely and percise identification of patients, who may benefit of the available both
experimental and marketed treatments and also favour biomedical research. The
general InNerMeD objectives are: a) to create a critical mass of multispecialist
knowledge to be disseminated in order to increase awareness on iNMDs among
physicians, patients and general stakeholders to anticipate diagnosis and, when
available, supply an adequate therapy; b) to straighten research capacities and foster
technological innovation; c) to provide practical support for sharing experiences at
global levels; d) to disseminate knowledge on clinical and experimental approaches for
diagnosis and treatment of iNMDs. It is expected that the network will provide: a) a
critical mass of competences instead of disperse expertise; b) validated customized
information about iNMDs; c) stimulation of innovative research projects to enforce
European leadership about iNMDs; d) identification of group of patients to be included
into biomedical research, registries and clinical trials; e) translation of scientific
breakthroughts into clinical practise; e) generation of social benefit to the aim of
establishing a standard of care for patients suffers from iNMDs across Europe. For
further information, please visit our website at: www.innermed.eu.
Milivoj Velickovic Perat
DEFINITION OF ALTERNATIVE MEDICINE AND COMPLEMENTARY MEDICINE
(CAM)
Academy of Developmental Medicine, Kranj, Slovenia, http://en.perat.eu
Already Aulus Cornelius Celsus (ca 25 BC – ca 50) suggested in De Medicina insanity
being the “mind at the mercy of imaginings” and described common practices of
bloodletting, incubation in temples, exorcism, as well as rical ways to restore rationality,
including starvation, stoning and beating.
Alternative medicine is any practice that is put forward as having the healing effects of
medicine, but is not based on evidence gathered with the scientific method. It may
consist of a wide range of health care practices, products and therapies, using methods
of medical diagnosis and treatments which were typically not included in the degree
courses of established medical schools teaching medicine. There are 1) Alternative
12
medical systems such as Chinese medicine and homeopathy, 2) Mini-body
interventions such as meditation, hypnosis, and prayer, 3) Biological-based therapies
such as herbal medicines, shark cartilage for arthritis and cancer and megavitamins, 4)
Manipulative and body-based therapies such as chiropractic manipulation and
massage, 5) Energy therapies such as magnetic therapy, therapeutic touch and light
therapies. Complementary medicine is alternative medicine used together with
conventional medical treatment in a belief, not proven by using scientific methods, that
it "complements" the treatment. CAM is the abbreviation for Complementary and
alternative medicine. Integrative medicine (or integrative health) is the combination of
the practices and methods of alternative medicine with evidence–based medicine.
Surveys about the use of CAM in the paediatric population shows that 11% of healthy
children were involved with CAM treatment, especially over-the-counter herbal
medication (Spigelblatt et al. Pediatrics 1994). A survey of 213 families whose children
were diagnosed as having Cerebral palsy shows that 56% of children received CAM
treatment (Hurvitz et al DMCN 2003). The individuals who received such treatment
were younger and more impaired than those who were not receiving CAM treatment(s)
and the parents of these children receiving CAM tended to be more educated and were
receiving CAM treatment themselves. 2006 Survey from Leeds UK shows that 3 of 25
healthy children received CAM, 14 of 25 patients with CP received CAM, 10 of 25 with
inflammatory bowel disease, and 6 of 25 with oncological problems were being treated
with CAM (McCann et al. Arch Dis in Childh. 2006). We should distinguish between
method, technique and approach in discussion especially in a therapeutic perspective.
What are the potentials of the developing brain of the individual person to adapt to and
to compensate for the damage we do not know? The brain is most plastic while brain
development is most rapid. Gender, religion and age after adolescence did not affect
the placebo response. Children below the age of 8 – 10 years do not understand the
concept of placebos but have higher placebo responses.
The only one »best« treatment for all problems of people with neurologic and/or
developmental abnormalities does not exist, but there is no doubt that if we start to
treat a problem early on; we will achieve better results (Veličković Perat M, 1976). But,
no maters of the epoch, ethical practice will not guarantee even the best available
technology used. A wrong aetiological conceptualization does not excuse an unethical
practice.
Igor Ravnik
COMPREHENSIVE MANAGEMENT OF SEVERE EPILEPSIES IN COUNTRIES
WITH LIMITED RESOURCES: the case of small populations*
Centre for Epilepsy, Dpt Child Neurology, UMC Ljubljana, Slovenia, and Slovenian
Chapter ILAE
Introduction: In Europe, 54 millions live in 24 countries < 5 million; 12,5 millions live in
countries < 3 million inhabitants. High professional expertise is needed everywhere.
Adjusted solutions are needed for rare / severely affected PwE in small systems.
Systems of care transplanted from large to small populations may not be most
appropriate. Models effective in small health systems may be applicable to larger
populations. Living with epilepsy in a small country is a unique challenge, and so is
implementing comprehensive care for people with epilepsy (PwE). Small population
require adjusted systems of care; often hard to implement due to limitations in
economy and politics. Small population also means less patients referred, and limited
professional expertise that may adversely affect e/quality of care. National languages
spoken by small populations make use of foreign facilities difficult. There is a special
risk to neglect patients affected by rare syndromes, requiring specific treatments.
13
Methods: Retrospective: example of Slovenia is used to illustrate solutions in health
care in a small population In 2 millions. Cumulative incidence of epilepsy was 4,58 /
1000 in 1988 (age 0-18 y), assuming 2400 patients with epilepsy, 10 000 pts »accross
the epilepsy spectrum«, 600 - 800 with resistant epilepsy.
Results: The three of assumedly most challenging issues in comprehensive epilepsy
care in small populations are related to a) surgically amenable resistant epilepsies, b)
psychosocial co-morbidity, c) rare epileptic disorders
Patients with difficult-to-treat, resistant epilepsies and epilepsy surgery: Lesional
surgery has been performed in Slovenia for all age groups. 18 years of weekly tertiary
multidisciplinary expert team meeting and Phase I presurgical assessement allowed to
select optimal candidates for sugery (performed in quartary centres abroad as the
population is too small to develop own paediatric epilepsy surgery). >800 patients have
been seen by staff meetings, 70 referrals, and >50 surgeries performed abroad. Patient
mobility has been supported by National Health Insurance (NHI) covering medical
costs. Volunteer accompaniment projects have been organized at non-governmental
level (ILAE and IBE Chapter) to facilitate care in foreign-speaking institutions. Recently,
NHI started covering specific acts of a mobile professional for the most demanding
cases. Priority goals: funds for staffing and specific professional education, specific
structures to be formally established (Epilepsy Monitoring Unit, Tertiary Epilepsy
Programme), recognition of additional worklod in collaborative cross-border patient
management.
Patients with psychosocial comorbidity. Effective model combining hospital and
extramural medical, psychological and remedial teaching expertise with nongovernmental networks in the community (»sector« model) in the past proved more
successful than the recent less integrated system of mental health (fragmentation of
services as s result of political change)
Critical issue: lack of interest in neuropsychiatric issues of epilepsy since neurology
and psychiatry separated, lack of dedicated professional inputs in the psycho-social
domaine, no institution or programme available for neurological patients with severe
psychiatric co-morbidity especially if acccompanied by adverse social situations.
Priority goals: structuring comprehensive teams, also at regional levels, including outreach activities.
Patients with rare epileptic disorders. Numbers of cases diagnosed in Slovenia roughly
correspond to (published) data, e.g.: Dravet sy (6), LKsy (4), ULDS (5), ring20chr (4),
hypothalamic hamartoma (1), Gastaut Geschwind sy (1). They are managed locally
with second opinions from centres with larger experience when needed, and much
stress on the staff. Priority goal: funding for regular professional up-date on rare
diseases, now nonexisting
Conclusions: Problems related to epilepsy comprehensive care in a small countries
do not differ in nature or epidemiology from those in large populations yet require
adjusted approaches making use of all available (limited) resources within the country
(professional, non-governmental) and in crossborder collaboration. Specific expertise
needs to be cultivated in postgraduate education for doctors and allied professions
related to specific areas of competence. Collaborative projects to link neighbour or
culturally / linguistically closer health systems from«small countries«, especially in the
field of resistant surgically amenable epilepsies, psychosocial co-morbidity and rare
epileptic syndromes, would be welcome, on international / regional level.
* collection of specific data in the countries of the region underway at the time of abstract submission.
Smail Zubčević
14
NEURODEVELOPMENTAL OUTCOME FOLLOWING THERAPEUTIC
HYPOTHERMIA FOR PERINATAL ASPHYXIA
Pediatric Hospital, University Clinical Center Sarajevo, Bosnia and Herzegovina
Hypoxic-ischemic encephalopathy (HIE) in newborns represents a major cause of
death and disability worldwide, without available specific therapies. HIE is acute or
subacute brain injury often due to perinatal asphyxia and represents an evolving
process. In primary phase initial injury is due to hypoxia-ischemia with primary brain
oxidative metabolism impairment. It is followed by a reperfusion period during which
the brain oxidative metabolism recovers partially or completely. That period is latent
phase or „window of opportunity“ in which we try to react, before secondary phase
during which brain cells continue to die for longer periods. Studies have found that
severity of this delayed energy failure is correlated with adverse neurodevelopmental
outcome at one and 4 years of age. It has be shown that reducing core body
temperature minimizes long-term neural consequences in animal models. Nowadays,
there are lot of studies supporting neuroprotective benefit of therapeutic hypothermia in
term newborns with HIE. There are different protocols followed around the world, but
mainly they consist of 72 hours of moderate hypothermia started within 6 hours of birth,
with period of subsequent controlled warming. Most of the studies agree that such
procedure reduces the rate of death and disability at 18 months of age. On the other
pole, lots of clinicians were pointing out that data in these studies were often
incomplete and inadequate to permit any comment on neurodevelopmental outcomes,
and did not answer such things as whether the efficacy of hypothermia is moderated by
the severity of encephalopathy. Therapeutic cooling of term neonates with HIE has
started at Paediatric Hospital in Sarajevo more than 2 yeas ago, and we have tried to
share our experiences in 23 patients that were treated that way. Neurodevelopmental
outcome in different stages of follow up, and contribution of some factors to overall
outcome are shown.
Nina Barišić, Branka Bunoza, Petra Grđan, Ivan Lehman, Goran Tešović 1
AUTOIMUNE ENCEFALOPATIJE U DJECE: KLASIFIKACIJA, DIJAGNOSTIKA I
LIJEČENJE
Klinika za pedijatriju KBC Zagreb, Medicinski fakultet Sveučilišta u Zagrebu
1
Klinika za infektivne bolesti „Dr. Fran Mihaljević“, Medicinski fakultet Sveučilišta u
Zagrebu
Encefalopatije u djece različite su etiologije i zahtijevaju složeni dijagnostički i terapijski
pristup. Autoimune encefalopatije klinički se manifestiraju znakovima limbičkog ili
difuznog encefalitisa, a prema etiologiji se mogu podijeliti u paraneoplastične i
neparaneoplastične autoimune encefalopatije.
Simptomi i znakovi autoimunog encefalitisa (AE) su vrlo varijabilni i najčešće uključuju
glavobolju, epileptičke napadaje i nerijetko epileptički status, poremećaje kretanja
(ataksiju, diskinezije, koreu, distoniju i tremor), promjenu ponašanja, kognitivne
poremećaje, poremećaje pamćenja, psihoze te različite stupnjeve poremećaja svijesti.
Faciobrahijalni distonički napadi mogu prethoditi razvoju limbičkog encefalitisa (LE).
Autonomna disfunkcija, poremećaji spavanja i hipoventilacija često se očituju u okviru
AE. Razvoj autoimunih encefalopatija mogu osim antigena tumora potaknuti virusni
antigeni no najčešće okidači ostaju neidentificirani.
15
Prema lokalizaciji antigena dijele se u AE uzrokovane antitijelima na intracelularne
antigene (Ma2,CV2/CRMP5 i Hu) i u odraslih su češće nego u djece paraneoplastičke
etiologije. Slabo reagiraju na imunoterapiju. AE uzrokovani protutijelima na površinske,
odnosno sinaptičke antigene (NMDAR, GluR5, LGI, AMPAR i GAD),i dobro reagiraju
na imunoterapiju.
Različiti imunološki uvjetovani poremećaji kretanja u pravilu se pojavljuju u AE.
Orofacijalne diskinezije i korea osobito su izraženi u encefalitisu uzrokovanom
protutijelima na NMDAR, CRMP 2. Hipokinezija i rigiditet tipično su udruženi s
protutijelima na Ma2. Ataksija i tremor pojavljuju se udruženi s anti Yo antitijelima
dok su ataksija i pseudoatetoza udruženi s anti Hu protutijelima i često su
paraneoplastične etiologije.
Antitijela u AE se dokazuju u likvoru i serumu. U cerebrospinalnom likvoru se nalazi
blaga pleocitoza, i/ili oligoklonske vrpce, a nerijetko je nalaz u likvoru normalan. EEG
pokazuje difuzne encefalopatske spore disritmičke promjene ili tzv. ekstremne delta
četke te žarišne epileptogene promjene odnosno paroksizmalna izbijanja u LE. MR
mozga je u pravilu normalan ili pokazuje prolazne sub/kortikalne T2 hiperintenzitete.
Rano prepoznavanje AE je od izuzetnog značaja zbog potrebe adekvatnog liječenja
imunoterapijom i posebno zbog mogućnosti ranog otkrivanja tumora i pravovremenu
primjenu odgovarajuće terapije.
Ljerka Cvitanovic-Sojat1, Ana Bielen2, Masa Malenica1, Monika Kukuruzovic1, Tamara
Zigman1, Kristina Kuznik1
CLINICAL PRESENTATION AND MOLECULAR ANALYSES IN SIBLINGS WITH
NIEMANN PICK TYPE C DISEASE
1
Department of Pediatrics, Neurology Unit, UHC Sestre milosrdnice; 2Faculty of Food
Technology and Biotechnology; Zagreb, Croatia
INTRODUCTION: Niemann-Pick disease type C (NP-C, OMIM 257220) is an
autosomal recessive disorder caused by mutations in NPC1 (95%) and NPC2 genes.
Incidence of NP-C is 1:150,000 live births. NPC1 is large glycoprotein involved in efflux
of cholesterol from late endosomes and lysosomes. Accumulation of unesterified
cholesterol is causing various neurovisceral symptoms. Age of onset varies with
neonatal, early infantile (2 months-2 years), late infantile (2-6 years), juvenile (6-15
years) and adult forms (>15 years). Major systemic symptoms include foetal
ascites/hydrops, neonatal cholestasis and (hepato)splenomegaly. Neurological
symptoms are: delay in motor milestones and hypotonia, gait problems, clumsiness,
speech delay, cataplexy, school problems, ataxia, seizures, psychiatric problems,
ataxia, dystonia, dementia and vertical supranuclear gaze palsy. The diagnosis is
confirm by histological, biochemical and genetic tests.
CASE STUDY: Two siblings (female born 1987, male born 1992) were born after
uneventful pregnancy and delivery. They had neonatal cholestasis, 3 months following
birth jaundice was resolved for both of them. Developmental milestones were reached
normally. The female had 5 years at the onset of first neurological symptoms: lost of
interest and concentration, poor drawing abilities. In the age of 7 years she developed
dysrhythmic EEG and slight mental retardation. CT of the brain and laboratory tests
were normal. At the age of 9 MR of the brain showed demyelination (in frontal and
occipital region). Skin biopsy revealed lipid inclusions in dermal axons and NP-C was
confirmed by filipin test (existence of perinuclear vesicles with accumulated unesterified
cholesterol). Intractable epilepsy occured, she also had insomnia. At 11 years she was
16
in the vegetative state and gastrostomy had to be applied, she died at 11 years and 10
months. Male sibling had earlier onset and faster progress of the disease. First
symptoms of NP-C appeared as very slow speech development, followed by behavioral
and cognitive problems (hyperactivity, poor memory, slurred speech). MR revealed
demyelination in occipital part of the brain. No lipid inclusions were found in skin
biopsy. Filipin test was positive and led to diagnosis. At the age of 6, epilepsy fits
started, dysartria and ataxia appeared. He died when he was 9,5 years old.
CONCLUSION: Molecular analysis confirmed that both siblings are compound
heterozygotes for two disease-causing mutations in NPC1 gene. NPC1 allele with
mutation A3467G in exon 22 codes for defective protein (N1156S), while C2764T in
exon 18 causes nonsense mutation (Q922X). This mutation was found only in genomic
DNA, while associated cDNA was not detectable. In late childhood when progressive
neurological symptoms develope and with previous history of neonatal cholestasis, a
classical late infantile type of NP-C must be suspected. Miglustat (Nbutyldeoxynojirimycin OGT-918) was under investigation when the famel sibling had a
diagnosis of NP-C. Following insufficient informations about the pharmacokinetics,
efficacy and safety in NP-C patients, the male sibling did not enter in a clinical trial.
Vlasta Đuranović, Vlatka Mejaški Bošnjak, Lucija Lujić, Goran Krakar, Tomislav
Gojmerac, Ivana Đaković
PROGRESIVNA OKLUZIVNA CEREBRALNA ARTERIOPATIJA U DJECE
Klinika za pedijatriju, Klinika za dječje bolesti Zagreb, Klaićeva 16, 10000 Zagreb
Progresivna okluzivna cerebrovaskularna arteriopatija (Moyamoya bolest/ sindrom) ,
sve se češće registrira u djece kao uzrok ishemijskog moždanog udara. Ako se na
vrijeme ne liječi, može dovesti do teških trajnih neuroloških oštećenja. Karakterizirana
je progresivnim suženjem (i konačno, okluzijom) terminalnog dijela unutarnje karotidne
arterije i proksimalnih dijelova srednje i prednje moždane arterije, s posljedičnim
stvaranjem kolateralne cirkulacije u području talamusa i bazalnih ganglija. Krvne žile
koje predstavljaju kolateralni protok u područjima hipoperfuzije mozga distalno od
mjesta stenoze, na DSA izgledaju poput „ dima cigarete“ , što se na japanskom zove
„moyamoya“. Najveća incidencija bolesti nađena je u Japanu.
U ovom radu, prikazat ćemo 6 bolesnika, koji su u različitoj životnoj dobi i s različitom
kliničkom slikom, primljeni u našu Kliniku, a kod svih je obradom dokazana
progresivna okluzivna cerebrovaskularna arteriopatija (Moyamoya bolest/ sindrom).
Kod pet od šest bolesnika je učinjena neurokiruška revaskularizacija s promjenljivim
ishodom. Naša najmlađa bolesnica je imala izrazito progresivan tijek bolesti s
razvojem tetrapareze, epilepsije, sljepoće, motorne afazije i disfagije. Ostali bolesnici
imali su bolji ishod. Važno je na vrijeme postaviti dijagnozu i time spriječiti teška trajna
neurološka oštećenja.
Matilda Kovac Sizgoric¹, Zlatko Sabol¹ , Tomislav Grmoja², Svjetlana Bela Klancir¹,
Zdravka Gjergja¹, Ljiljana Kipke Sabol¹, Filip Sabol³
MASA SYNDROME - REPORT OF A TWO TWIN BROTHERS
17
¹Sabol Clinic for Sick Children ,²Departmet of Radiology, ²Children Hospital
Zagreb, ³Department of Psychiatry, University Hospital Rebro, Zagreb, Croatia
E-mail: [email protected], [email protected]
Introduction : MASA syndrome, also called CRASH syndrome and Gareis-Mason
syndrome, is a rare X-linked recessive neurological disorder.The acronym "MASA"
describes four major symptoms - mental retardation, aphasia, shuffling gait, and
adducted thumbs. A more suitable name for this syndrome is "L1 syndrome". The
disorder has been associated with mutations in the L1CAM gene. This syndrome has
severe symptoms in males, while females are carriers because only one Xchromosome is affected.
The aim of this report is to show similarities and differences between clinical
manifestations in twins with the L1CAM gene mutation and highlight the importance of
genetic analysis in explaining the etiology of unclear cases in pediatric neurology.
Our patients: Born prematurely at 35 weeks gestation. Pregnancy was complicated
with early bleeding and gestational diabetes. Immediately after birth hypertonus of the
lower extremities in both twins was observed. Sixteen-year clinical follow-up showed
spastic paraparetic form with shuffling gait, clumsiness, delayed speech development,
with lower intellectual functioning at the level of light to moderate mental retardation,
primary nocturnal enuresis, behavioral and sleep disorder (more pronounced in the
second twin). Brain MRI in both twins showed complete agenesis of the corpus
callosum, complete lack of the anterior commissure, and internal hydrocephalus.
EEGs showed nonspecific slower dysrhythmic changes. Kidney ultrasounds showed
mild dilatation in the channel system of both kidneys in both twins. Ophthalmologic
examinations was normal. Molecular genetic testing (Karl-Franzens Universität Graz)
identified homozygous intron 26 L1CAM gene mutation IVS26-12G → A in both
twins.The mother is a carrier of the same heterozygous mutations.
Conclusion: Our patients, the twins show similar clinical changes typical of MASA
syndrome. After identifying the specific genetic mutations this family has become
informative for prenatal diagnosis.
Radenka Kuzmanić Šamija, Maja Tomasović
Poremećaji kretanja kao simptom paraneoplastičnih i autoimunih procesa
Klinički odjel dječje neurologije i endokrinologije, Klinika za dječje bolesti Split, Klinički
bolnički centar Split
Poremećaji kretanja koji su prije uglavnom svrstavani u grupu idiopatskih ili
degenerativnih poremećaja živčanog sustava danas se, u većini slučajeva, prepoznaju
kao imunološki uzrokovani poremećaji. Neki od njih su paraneoplastični i povezani su
sa stvaranjem antitijela na antigene stanične membrane ili sinaptičke proteine.
Paraneoplastični neurološki sindromi su rijetki poremećaji dječje dobi, imaju nepovoljni
učinak na djetetov mozak u razvoju. Mogu zahvatiti bilo koji dio živčanog sustava, ali
centralni živčani sustav je najčešće zahvaćen s razvojem ataksije, diskinezije, choree ili
distonije. Prevalencija za dječju dob je nepoznata.
Prikazati će se klinička slika najčešćih paraneoplastičnih sindroma dječje dobi:
opsoklonus mioklonus ataksija sindrom (OMAS), limbički encefalitis i Anti-N-metil-D18
aspartat receptor (anti-NMDA-R) encefalitis, imunološka podloga razvoja bolesti,
dugoročne posljedice te terapijske mogućnosti liječenja tih sindroma.
Pravovremeno prepoznavanje paraneoplastičnih sindroma u djece omogućuje rano
otkrivanje, a time uspješnije liječenje maligne bolesti, također pravovremena terapija
neuroloških simptoma, koji ponekad mogu biti glavni uzrok smrti djece kod koje je
inače uspješno izliječena maligna bolest, pridonosi smanjenju stope mortaliteta i boljem
neurološkom ishodu. Dječji neurolog ima najvažniju ulogu prepoznavanju bolesti,
otkrivanju tumorskih procesa i liječenju neuroloških simptoma nakon završenog
onkološkog liječenja.
Ključne riječi: paraneoplastični neurološki sindromi, opsoklonus-mioklonus ataksija,
encefalitis, dječja dob
Igor Prpić, Antun Sasso, Tea Ahel, Petar Vukelić
NEUROIMAGING INDICATIONS IN MANAGEMENT OF CHRONIC DAILY
HEADACHE IN CHILDREN
Department of Pediatrics, Clinical Hospital Centre Rijeka, Rijeka
AIM: In every day’s practice neuroimaging studies are still frequently performed in
management of childhood headache. The aim of this study was to determine whether
there is significant discrepancy between clinical practice and clinical practice guidelines
on indications for neuroimaging studies.
PATIENTS AND METHODES: The medical records of children treated for headache in
the Clinical Hospital Center, Children’s Hospital »Kantrida«, Department of Pediatric
Neurology were retrospectively reviewed. The study focused on children with chronic
daily headache, ranged in age from 2 to 18 years. MRI/CT scanning indications were
revised and compared to clinical practice guidelines.
RESULTS: Brain imaging was performed in 164 (76.3%) of 215 children with chronic
headache; MRI in 93 (43.2%) and CT in 71 (33.0%) children. Indications were as
follows: anxiety and/or insistence of child’s families (n=117, 54.4%), presence of
associated features that suggest neurologic dysfunction (n=22, 10.2%), age under the
5 years (n=21, 9.8%) and abnormal neurologic examination (n=4, 1.9%).
The majority of children (117/215=54.4%) had normal neuroimaging findings. MRI/CT
revealed different intracranial/extra-cranial findings
(pineal cysts, foci of gliosis,
cortical atrophy, sinusitis, adenoids enlargement etc.) not influencing changes in the
headache management, (47/215=21.9%).
Only one patient (1/215=0.46%) (with abnormal neurological examinations in which
MRI revealed brain tumor), required change in the headache management after
MRI/CT.
CONCLUSION: The yield of brain imaging in this study group was 48/215=22.3%,
which corresponds to results of similar studies in children with chronic headache. More
than 50% of neuroimaging studies were performed due to the parent’s fear/insistence.
In this group all findings were benign and neither one required changes in management
of headache. This study proves that, despite available evidence-based clinical
guidelines, brain imaging in children with chronic headaches is overused, mostly in
order to decrease anxiety of family/patient. Physicians should devote more time in
explaining the nature of headache to patients and families, resulting in their anxiety
reduced.
19
Romana Gjergja Juraški, Mirjana Turkalj, Ivana Marušić
POREMEĆAJI SPAVANJA U DJECE S KROMOSOMOPATIJAMA, GENSKIM
POREMEĆAJIMA I NASLJEDNIM SINDROMSKIM OBRASCIMA
Odjel neuropedijatrije, Odjel za poremećaje spavanja u djece, Dječja bolnica Srebrnjak,
Zagreb
Utjecaj gena, okoline te interakcije gena i okoline u poremećajima spavanja sve je
prepoznatljiviji zadnjih godina. Dobro dokumentirane studije spavanja u obiteljima te
studije blizanaca s poremećajima spavanja ukazale su na važnost genetskih
čimbenika. Do danas je u nekoliko rijetkih poremećaja pretpostavljena mutacija u
jednom genu kao uzrok smetnji: fatalna obiteljska insomnija, obiteljski sindrom pomaka
faze spavanja, kronična primarna insomnija te narkolepsija s katapleksijom. Međutim,
mnogi poremećaji spavanja u djece su izrazito klinički i fenotipski kompleksni. Zadnje
linkage i genomske studije su rezultirale u pronalasku genskih mutacija, lokalizacija
uzročnih gena te gena kandidata za nekoliko vrsta poremećaja spavanja te nam
omogućile bolje razumijevanje patogeneze poremećaja spavanja, procjene rizika,
prognostike te ciljane terapijske mogućnosti kao i mogućnost prevencije. Djeca s
kromosomopatijama, genskim poremećajem te nasljednim sindromskim obrascem
često imaju i poremećaj spavanja koji nije uvijek na vrijeme uočen i evaluiran. U
trogodišnjem razdoblju (rujan 2010 - rujan 2013) analizirali smo prisutnost poremećaja
spavanja u skupini djece s neurološkom simptomatologijom vezanom uz različite
nasljedne poremećaje (kromosomopatije, genski poremećaji te sindromski obrasci
nepoznate etiologije). Poremećaj spavanja smo evaluirali cjelonoćnim 16-kanalnim
EEG monitoringom i cjelonoćnim polisomnografskim studijama. Analizirali smo
povezanost genetske podloge osnovne bolesti s poremećajem spavanja u ove djece.
Najčešći poremećaji spavanja bili su poremećena arhitektura spavanja, fragmentirano
spavanje, insomnija, centralna i opstruktivna apneja u spavanju, a najčešći negativni
čimbenici za poremećaje spavanja bili su debljina, hipotonija, kraniofacijalna dismorfija
i mentalni deficit. Preporučamo u djece s neurološkom simptomatologijom vezanom uz
nasljedne sindromske obrasce, kromosomopatije i genske poremećaje evaluirati i
postojanje poremećaja spavanja kao negativnog prediktora za mentalni deficit, smetnje
pažnje i ponašanja, prekomjernu dnevnu pospanost, paroksizmalne noćne događaje,
tvrdokornost epilepsije, debljinu, respiratornu insuficijenciju te bolesti srca i krvnih žila.
Maša Malenica, Monika Kukuruzović, Suzana Bitanga, Goran Krakar1, Ljerka
Cvitanović-Šojat
RAZLIČITE KLINIČKE PREZENTACIJE ISTE MUTACIJE - FRIEDREICHOVA
ATAKSIJA
Odjel za neuropedijatriju, Klinika za pedijatriju, Klinički bolnički centar Sestre
milosrdnice, Zagreb; 1Klinika za pedijatriju, Klinika za dječje bolesti Zagreb, Zagreb
Cilj: Prikazati dva različita klinička fenotipa u brata i sestre kao posljedice dinamičke
mutacije tj. povećanog broja tripleta GAA u intronu 1 gena za frataksin (FXN) na 9.
kromosomu na oba alela. Kod oboje se radi o alelima s punom mutacijom (> 600
neprekinutih niza tripleta GAA). Različite kliničke prezentacije očekivale bi se kod
složenih heterozigota odnosno kod homozigota s premutacijskim alelima.
Prikaz bolesnika: Djevojka u dobi 15 godina sa skoliozom primljena je na obradu
povremenog tremora. Neurološkim se pregledom uoči blaga ataksija, tremor i
nistagmus. Obradom se nađe neurografski nalaz potpunog gubitka senzornih
20
potencijala uz znakove demijelinizacije i granične brzine provođenja nadonjim
ekstremitetima. Kardiološkom obradom nađena je koncentrična hipertrofična
kardiomiopatija, i hipertenzija. Njezin mlađi brat nikada nije imao niti jedan od sestrinih
simptoma, a analiza DNA učinjena je tek nakon što je utvrđena izuzetna koncentrična
hipertrofična kardiomiopatija. Kod oboje je utvrđena puna mutacija frataksina na
kromosomu 9. Kod oboje je uz terapiju ACE inhibitorom došlo do normalizacije tlaka.
Kod sestre je neurološko propadanje vodeći simptom, dok je kod brata isključivi
problem progresivna hipertrofična kardiomiopatija.
Kod sestre je neuspješno
provedena potporna terapija idebenonom, koenzimom Q10 i vitaminom E.
Zaključak: Naš prikaz upućuje da je izuzetno važno razmatrati postojanje neurološkog
oboljenja i kod odsustva tipičnih neuroloških ispada. Kod prisustva koncentrične
hipertrofične kardiomiopatije obavezno je posumnjati na FA. Ovo je rijedak slučaj kod
oboljelih od FA s alelima s punom mutacijom i brojem GAA iznad 600 a vrlo različitom
kliničkom slikom. Zbog multisistemnog zahvaćanja nužan je trajan multidisciplinarni
pristup
koji kod
naših
bolesnika
za
sada
uključuje
neuropedijatra,
kardiologa,nefrologa,ortopeda,fizijatra, fizioterapeuta,ORL specijalistu, oftalmologa i
psihologa. Upravo zbog ovakvog slučaja važna je potreba za opsežnom obradom pri
postavljanju dijagnoze i liječenju oboljelih od Friedreichove ataksije (FA)-autosomno
recesivne neurodegenerativne bolesti.
Dunja Čokolić-Petrović, Krasanka Hafner, Bahrija Lenz, Martina Katić
NASLJEDNA TROMBOFILIJA KAO RIZIČNI FAKTOR ZA NASTANAK MOŽDANOG
UDARA U NOVOROĐENAČKOJ DOBI
Miroslav Gjurašin, Vlatka Mejaški-Bošnjak, Vlasta Đuranović, Tomislav Gojmerac,
Goran Krakar, Ljiljana Popović
ZBRINJAVANJE VASKULARNIH MALFORMACIJA MOZGA U DJECE
Klinika za dječje bolesti Zagreb, Klaićeva 16, 10000 Zagreb
Uvod
Vaskularne malformacije mozga u djece obuhvaćaju kavernome, arteriovenske
malformacije, venske angiome, kapilarne teleangiektazije te aneurizme. Specifične su
po lokaciji, kliničkoj prezentaciji, načinu dijagnostike, mogućnostima liječenja te ishodu.
Kako postupati s ovim tvorbama u djece, predmet je ovog rada.
Materijal i metode
U Klinici za dječje bolesti Zagreb Klaićeva liječeno je ukupno 46 bolesnika s
dijagnosticiranom vaskularnom malformacijom mozga. U prospektivnom istraživanju
analizira se klinička prezentacija te dijagnostički i terapijski postupak.
Rezultati
Od 46 bolesnika dječje dobi (0-18 godina) s vaskularnim malformacijama, većina se
prezentirala venskim angiomom (22), zatim arteriovenskom malformacijom (9),
kavernomom (7), aneurizmom (2), kapilarnom teleangiektazijom (1), aneurizmom vene
Galeni (2), te kombiniranom ekstra-intrakranijskom vaskularnom tvorbom (3). Klinička
slika obuhvaćala je epi napad, krvarenje, glavobolju, neurološki deficit ili asimptomatski
nalaz. U 17 bolesnika učinjena je neurokirurška operacija, u 4 bolesnika embolizacija, a
preostali su liječeni konzervativno ili praćeni ambulantno. Većina operiranih bolesnika
21
oporavila se bez deficita u neurološkom statusu. Jedna 8-godišnja bolesnica s
moždanom komom uzrokovanom krvarenjem u pons i potom operiranom avmalformacijom ponsa sa zaostalim teškim neurološkim deficitom facio i bulbomotorike
s hemiparezom postupno se značajno oporavila tijekom ukupno 3 godine rehabilitacije.
Jedan bolesnik u dobi 15 godina je na dan postavljanja dijagnoze cerebralne
aneurizme umro zbog nagle rupture aneurizme, a jedna bolesnica i dobi od 13 godina
umrla je nakon masivne intracerebralne hemoragije duboke av-malformacije. Većina
bolesnika s venskim angiomom je asimptomatska, a među simptomatskima jedan je
bolesnik dobi 14 godina s udruženim infratentorijskim kavernomom malog mozga u
području krova IV komore uspješno operiran nakon rupture i rerupture kavernoma, bez
većeg neurološkog deficita izuzev centralnog unilateralnog oštećenja sluha nejasne
geneze.
Zaključak
Bolesnici dječje dobi s vaskularnom malformacijom mozga razlikuju se po kliničkoj
prezentaciji, tipu malformacije, načinu liječenja i prognozi. Pravodobna dijagnostika i
adekvatno provedeno operativno ili embolizacijsko liječenje značajno doprinose
oporavku funkcija i izlječenju.
Ljiljana Popović-Miočinović, Katarina Bošnjak Nadj
MIGRENA I EPILEPSIJA U OBITELJI DJECE SA CEREBRALNOM PARALIZOM
Specijalna bolnica za zaštitu djece s neurorazvojnim i motoričkim smetnjama, Goljak
2., Zagreb
Uvod: Danas se vjeruje da epilepsije (simptomatske) kod cerebralne paralize nisu
jednostavna posljedica oštećenja mozga nego i brojnih genetskih i epigenetskih
čimbenika, koji moduliraju procese sazrijevanja oštećenog mozga, neuronalne mreže i
dovode do epileptogeneze, primarne i/ili sekundarne. Patofiziološki mehanizmi
komorbiditeta migrene i epilepsije nisu u potpunosti razjašnjeni. Postoje hipoteze da bi
povećana kortikalna ekscitabilnost, koja obilježava obje bolesti, mogla predstavljati
zajednički patogenetski mehanizam.
Cilj: Ispitati učestalost migrena i epilepsija u obiteljima perinatalno oštećene djece sa
cerebralnom paralizom (CP).
Metodologija: Izabrano je 134 cerebralno paralizirane djece starije od 5 godina sa
dokazanim perinatalnim oštećenjem (UZ/CT/MR mozga). Grupa ispitanika (N=67) je
imala CP i epilepsiju, a kontrolna grupa CP (N= 67). Podaci o migreni i epilepsiji u
obitelji (majka,otac,braća i sestre) prikupljeni su po izjavama roditelja, a u manjeg broja
priložena je i medicinska dokumentacija obitelji. Statisička obrada učinjena je X2
testom.
Rezultati: Statistički su testirane 22 varijable vezane uz neurorizične faktore, tijek i
kliničku sliku CP u ispitanika i kontrola. Dokazano je da su grupe sukladne, osim po
dvije varijable: novorodjenačke konvulzije i hemiparetički oblik CP (statistički su
značajno češći u ispitanika).
U obitelji ispitanika i kontrola migrenu je imalo 15/13 (22 %/19%), epilepsiju 10/6
(15%/9%), udruženu migrenu i epilepsiju 7/1 (10%/1,5%).
Statistički je dokazano da je migrena u obitelji podjednako učestala u ispitanika i
kontrola, epilepsije u obitelji su češće u ispitanika (bez statističke značajnosti), dok su
migrena i epilepsija u obitelji ispitanika statistički značajno češće (P = 0,0286).
Karolina Župetić, Desa Grubić Jakupčević
22
MOTIVACIJA CEREBRALNO PARALIZIRANOG DJETETA ZA TERAPIJU
Specijalna bolnica za zaštitu djece s neurorazvojnim i motoričkim smetnjama,
Goljak 2., Zagreb
Mogućnosti fizioterapije su široke. Svrha provođenja fizioterapijskog tretmana je
povećanje funkcionalnih sposobnosti djeteta, a krajnji cilj je osposobiti dijete za što
normalniji i samostalniji život.Terapija započinje u najranijoj životnoj dobi kroz handling
bebe i traje godinama kroz neurorazvojnu terapiju. U svemu nam je najbitnije dijete i
njegova cjelokupna ličnost sa svim njegovim potrebama. Kako je osnova samog
terapijskog tretmana „normalan pokret“ vodimo dijete kroz niz zanimljivih tjelesnih
aktivnosti kako bi izbjegli stereotipne vidove terapija koje stvaraju kod djeteta odbojnost
ka terapiji.
Tako nam je bazična terapija Bobath i terapija senzorne integracije kojima se
nadopunjuju radna terapija te govorna terapija.
Djeca se uključuju u terapiju u vodi kroz Halliwick koncept, jer im voda znatno olašava
pokrete, te im daje više zadovoljstva i samopouzdanja. Isti efekt daje i terapijsko
jahanje gdje dijete osjeća kretanje konja i taj se osjećaj kretenja prenosi na njega. Tako
svi vidovi terapije utječu na poboljšanje funkcije, posture ravnoteže i mobilnosti i daju
bolje terapijske rezultate kod djeteta.
Andrea Šimić Klarić, Zdravko Kolundžić, Vlatka Mejaški Bošnjak*
CEREBRALNA PARALIZA I PRIDRUŽENA NEURORAZVOJNA ODSTUPANJA U
DJECE S KORTIKALNOM DISGENEZOM
Dječji odjel, Opća županijska bolnica, Požega; *Klinika za dječje bolesti Zagreb,
Klaićeva 16, 10000 Zagreb
Kortikalna disgeneza predstavlja spektar anomalija mozga koje uključuju poremećaj
razvoja moždane kore nastao zbog poremećaja migracije neurona. Povezana je s
neurorazvojnim odstupanjima kao što su epilepsija, mentalna retardacija, cerebralna
paraliza i pridružena neurorazvojna odstupanja.
Prikazujemo dva dječaka s cerebralnom paralizom i pridruženim neurorazvojnim
odstupanjima uslijed kortikalne disgeneze. Prvi pacijent je dječak u dobi od 5 godina s
neupadljivom obiteljskom i urednom perinatalnom anamnezom. U dobi od 6 mjeseci
upućen je radi lijevostranog hemiparetskog razvoja. U elektroencefalogramu (EEG)
uočeno je žarište desno frontalno, a na magnetskoj rezonanci (MR) mozga vidljiva je
anomalija razvoja moždane kore u smislu operkulum sindroma desno. Provodi se
fizikalna terapija i logopedski tretman radi artikulacijskih poteškoća. Dosad nije imao
konvulzije.
Drugi pacijent je dječak koji razvija lijevostrani hemiparetski razvoj od dojenačkog
doba. Rođen je u 33. tjednu gestacije, a imao je i perinatalnu infekciju. Zbog povišenog
IgG na citomegalovirus, učinjen je PCR u urinu i serumu koji je bio pozitivan, ali bez
indikacija za terapiju ganciklovirom.
U dobi od 3 godine dječak pokazuje bilateralni spastični obrazac cerebralne paralize. U
EEG-u se registriraju šiljci preko desne hemisfere s tendencijom sekundarnoj
generalizaciji. Na MR mozga vidljiv je poremećaj migracije neurona u smislu pahigirije
obostrano. Kod dječaka se provode vježbe medicinske gimnastike, radna terapija, a i u
logopedskom je tretmanu zbog usporenog govorno-jezičnog razvoja. Dosad nije imao
konvulzije, a nalaz EEG-a je nepromijenjen.
Neurorazvojni ishod naših pacijenata s kortikalnom disgenezom obilježavaju
cerebralna paraliza s pridruženim neurorazvojnim odstupanjima, poremećajem
jezičnog razvoja, te rizikom za pojavu epilepije (žarišno promijenjen EEG). Kortikalnu
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disgenezu stoga treba uzeti u obzir kao mogući uzrok cerebralne paralize, a dijagnozu
je moguće postaviti samo magnetskom rezonancom mozga.
Miroslav Gjurašin, Goran Roić, Josip Marjanović, Tonći Grmoja, Ljiljana Popović
TUMORI LUBANJE U DJECE: PREPOZNAVANJE I LIJEČENJE
Klinika za dječje bolesti Zagreb, Klaićeva 16, 10000 Zagreb
Uvod
Palpabilne tvorbe na glavi djece prilično su čest klinički nalaz. Osim pravih tumora,
nalaze se uvećani limfni čorovi, hematomi nakon traume, prirođene neravnine kosti
lubanje, razne bolesti kože ili kalcifikati. Kako razlikovati ove tvorbe od pravih tumora
koji zahtijevaju obradu i liječenje predmet je ovoga rada.
Materijal i metode
U Klinici za dječje bolesti Zagreb Klaićeva u zadnjih 10 godina operirali smo 175 djece
s tumorom lubanje, koji su analizirani u dijagnostičkom i terapijskom postupku.
Rezultati
Najčešći tumor lubanje u dječjoj dobi je dermoidna cista, koja se prezentira većinom
kao palpabilna tvrda i dijelom kompresibilna tvorba nepomična od kosti. Suprotno
tome, eozinofilni granulom prezentira se klinički kao mekana potkožna masa
nepomična od kosti. Osteom lubanje odlikuje se tvrdim i nekompresibilnim
zadebljanjem kosti lubanje bez mogućnosti pomicanja. Rjeđi tumori lubanje kao
osteoblastom ili hemangiom mogu se prezentirati kao velike tvrde mase koje značajno
izbočuju pod kožu, ali je ne probijaju. Suprotno tome, zloćudni tumori lubanje poput
limfoma ili limfoblastoma pored kosti razaraju i meka tkiva i probijaju na kožu. Tumori
baze lubanje u djece su rijetki, no utiskuju u endokranijski prostor i strukture baze
mozga. Kod solitarnih benignih i malignih tumora terapija izbora jest radikalno kirurško
uklanjanje tumora u cijelosti. Kod multiplih zloćudnih tumora indicirana je biopsija.
Onkološka obrada i liječenje provodi se kod svih malignih tumora.
Zaključak
Uloga liječnika koji prvi pregledava dijete sa tvorbom na glavi jest utvrditi konzistenciju
tvorbe, pomičnost od kosti lubanje, ocijeniti da li je ugrožena trofika kože zbog pritiska
tvorbe odozdo, ispitati anamnestički brzinu rasta tvorbe, te planirati daljnju obradu.
Tumori lubanje većinom su dobroćudni i višemjesečni spori rast ostavlja dovoljno
vremena za kvalitetnu dijagnostiku i planiranje optimalnog liječenja što ima svoje
značenje poglavito u djece mlađe od godinu dana. Izrazito brzi rast tvorbe upućuje na
zloćudnost, i tu je potrebna žurna obrada.
Katarina Bošnjak Nadj, Ljiljana Popović Miočinović, Neda Striber*
ELEKTROFIZIOLOGIJA VIDA KOD DJECE
Specijalna bolnica za zaštitu djece s neurorazvojnim i motoričkim smetnjama,
Goljak 2., Zagreb, *Klinika za dječje bolesti,Klaićeva 16, Zagreb
24
Uvod: Elektrofiziloško ispitivanje vida kod djece omogućuje rano otkrivanje odstupanja
u razvoju vidnog sustava,razlikovanje oštećenja retine od vidnog puta, s ciljem
uključivanja u terapijske postupke. Međunarodna organizacija ISCEV (International
Society for Clinical Electrophysiology of vision) dala je preporuke i protokole za
ispitivanje vida kod odraslih koji se primjenjuju i za djecu stariju od 7 godina, dok za
dojenčad i malu djecu još nema standarda. U svijetu se koriste dvije tehnike: 1.
odvojeno snimanje elektroretinografije(ERG) i vidnih evociranih potencijala(VEP). Za
registriranje se koriste kornealne elektrode i dijete se sedira; 2. simulatano snimanje
ERG i VEP-a po GOSH (Great Ormond Street Hospital for Sick Children,London)
protokolu. Za ERG se koriste kožne elektrode postavljene ispod donje vjeđe, za VEP
tri elektrode iznad primarnog vidnog korteksa. Dijete je budno,sjedi u krilu roditelja.
Cilj:Prikazati GOSH protokol snimanja koji koristimo i u našoj Bolnici.
Metoda: ERG stimulacija se provodi Grass foto stimulatorom bijelim,crvenim,plavim
svjetlom i sa 30 Hz. VEP stimulacija Grass foto stimulatorom bijelim svjetlom za Flash
VEP i strukturiranim podražajem, „šahovnicom“,gdje se imjenjuju bijela i crna polja.
Kod "onset"(eng.)strukturiranog podražaja šahovnica se pojavljuje i nestaje na ekranu,
kod "reversal"(eng.) podražaja šahovnica je prisutna cijelo vrijeme, ali izmjenjuju
mjesta bijela i crna polja.
Rezultati: ERG odgovor na stimulaciju bijelim svjetlom daje nam informacije o funkciji
štapića,čunjića i bipolarnih stanica,ERG na crveno svjetlo i podražaj s 30 Hz govori o
funkciji čunjića,a ERG na plavo svjetlo o funkciji štapića. Flash VEP reflektira aktivnost
centralnog vidnog polja koja je došla do moždane kore, govori o integritetu vidnog puta
od mrežnice do primarnog vidnog korteksa i ev.o anomaliji križanja vlakana vidnog
živca. VEP sa strukturiranim podražajem govori o kvaliteti rezulucije strukture u
okcipitalnoj kori i oštrini vida.
Zaključak:Elektrofizološko ispitivanje vida GOSH protokolom je neinvazivna tehnika
simultanog snimanja ERG i VEP-a koja omogućuje vrlo rano diferenciranje retinalnih
od postretinalnih oštećenja vida.Nalaze je potrebno uvijek interpretirati uz klinički sliku.
Maja Jurin1, Nina Barišić1, Ratimir Petrović2, Johann Holthausen3, Tom Pipper3
OPERABLE AND INOPERABLE CASES OF DRUG RESISTANT EPILEPSY
1
University Hospital Center ZAGREB, Pediatric department, Division for Child
Neurology, Croatia
2
University Hospital Center Zareb, Division for nuclear medicine
3
Schon Klinik, Epilepsy Center for Children and Adolescents, Vogtareuth, Germany
We report on a good outcome of neurosurgical treatment in 5, 9 and 12years old male
patients suffering from drug resistant epilepsy. First patient had left frontal cortical
dysplasia type IIA, mild right hemiparesis and slightly retarded psychomotor
development (speech). Second one had congenital infarction of the right ACM (arteria
cerebri media), left spastic hemiparesis and cognitive devolpmental disturbances
caused by intractable epilepsy. The third and most complicated patient had focal
cortical dysplasia type II A bilaterally temporaly and haevy developmental retardation.
Patients will be presented through personal and family anamnesis, seizure semiology
as well as by reports about preoperative AED (antiepileptic drugs) treatment and all
diagnostics performed in Croatia (brain magnetic resonance (MR), single photon
emission computerised tomography (SPECT), standard EEG recordings and laboratory
tests, some metabolic investigations) before preoperative evaluation and epilepsy
surgery done abroad (Germany).
Methods performed in Epilepsy Surgery Center abroad included noninvasive long term
Video EEG monitoring (ictal and interictal, sleep and awake EEG), high resolution brain
25
magnetic resonance tomography (MRT) with epilepsy protocol (T1, T2, FLAIR, 3D T1
MPR sequences, DTI,) performed in general anaesthesia, functional brain MR,
invasive long term Video EEG monitoring with subdural plates, grids as well as with
deep electrodes, brain multislice-spiral-CT, intraoperative EEG –electrocorticography
(ECOG), psychological testings, panel diagnostics EIP02 and CGH Array diagnostics
for exclusion of epileptic encephalopathies.
The data obtained by thorough preoperative diagnostics will be shown.They were
congruent with the clinical semiology in our first and second patient who are succesfully
operated and are seizure free now. Week electroclinical morphological correlation in
the third patient proposed exsclusion of epileptic encephalopathies what is needed
before epilepsy surgery.
We expect the final good outcome of the neurosurgical treatment and the
discontinuance of the antiepileptic therapy in all presented patients.
Sanja Delin1, Linda Pavić1, Antun Sasso2, Irena Barbarić2, Goran Krakar3
KONGENITALNA MIOTONIČKA DISTROFIJA - PRIKAZ PACIJENTA
1
Opća bolnica Zadar, Zadar; 2KBC Rijeka, Klinika za pedijatriju Kantrida, Rijeka;
Klinika za dječje bolesti Zagreb, Zagreb
3
Miotonična distrofija ili Steinertova bolest druga je po učestalosti mišićna distrofija u
djetinjstvu,odmah
nakon
progresivnih
mišićnih
distrofija
(Duchenne
i
Becker).Incidencija u općoj populaciji je od 1:8000 u Europi do 1:30000 u Hrvatskoj,a
nasljeđuje se autosomno dominantno.Gen je lociran na dugom kraku 19 kromosoma
(19q13),genski produkt je miotonin proteinska kinaza.Bolest nastaje zbog dinamičke
mutacije tj. patološkog umnažanja sljedova identičnih trinukleotida CTG unutar gena za
miotonin protein kinazu (DMPK) na dugom kraku 19 kromosoma (19q13).U zdravih
osoba broj ponavljanja tripleta CTG iznosi 5-34 i ostaje stabilan tijekom generacija.Kod
bolesnih osoba slijed je produljen i sadržava od 50 do nekoliko tisuća trinukleotida
CTG,a težina kliničke slike i vrijeme javljanja bolesti koreliraju s veličinom mutiranog
gena.Osobe s brojem tripleta 35-49 (nositelji premutacijskog gena) zdravi su
prenositelji bolesti.Mutacija se češće prenosi preko majke, a svaka slijedeća generacija
nosi molekulski i klinički težu mutaciju (fenomen anticipacije).
Bolest se očituje simptomima više organskih sustava:zahvaćeni su proprečnoprugasti
mišići i glatki mišići crijeva, miokard i njegov provodni sustav,zahvaćeni su i endokrini i
imunološki sustav,razvija se katarakta,djeca mentalno zaostaju a postoje i neurološki
deficiti.
U
ovom
radu
prikazujemo
muško
novorođenče
s
generaliziranom
hipotonijom,facijalnom dizmorfijom,oskudnom mimikom,poteškoćama hranjenja i
deformitetima stopala.Iz obiteljske anamneze se saznaje da je sedmogodišnjem bratu
postavljena klinička sumnja na facio-scapulo-humeralnu mišićnu distrofiju.Ciljani
neurološki pregled majke otkrio je slabost mišića lica,nemogućnost čvrstog zatvaranja
očiju,akcijsku miotoniju ruku i perkusijsku miotoniju jezika.Sve to nas je uputilo na
molekularno genetsku analizu (kojom je utvrđen alel s punom mutacijom) i potrebu
genetskog ispitivanja cijele obitelji.
Ovim prikazom željeli smo upozoriti na nasljedni oblik neuromuskularne bolesti koja
zahtijeva detaljan klinički i neurološki pregled,detaljnu i sveobuhvatnu obiteljsku
anamnezu o mogućim prenositeljima bolesti kroz više generacija,detaljan klinički
pregled članova uže obitelji te ciljano neurofiziološko i genetsko testiranje.
26
Danijela Petković Ramadža1, Vladimir Sarnavka1, Mario Ćuk1,2, Lidija Paležac2, Ksenija
Fumić3, Karmen Bilić3, Marija Zekušić3, Višnja Hrustić1, Katarina Bošnjak Nađ4,
Gordana Mustać5, Neven Milić5, Ivo Barić1,2
NEURONOPATHIC TYPES OF GAUCHER DISEASE-DIAGNOSTIC AND
THERAPEUTIC CHALLENGES
1
Department of Paediatrics, University Hospital Centre Zagreb, Croatia
School of Medicine, University of Zagreb, Croatia
3
Clinical Institute for Laboratory Diagnostics, University Hospital Centre Zagreb,
Croatia
4
Special hospital for children with neurodevelopmental and motor disorders, Zagreb,
Croatia
5
Department of Paediatrics, General Hospital Zadar, Croatia
2
Gaucher disease is lysosomal storage disorder caused by low activity of enzyme
glucocerebrosidase and consequent deposition of glucocerebroside in the cells of the
macrophage-monocyte system. Traditionally, disease is divided into three clinical types
delineated by the central nervous system involvement and the disease progression.
Types II and III are so called neuronopathic forms. Type II is rapidly progressive and
results in death during the first two years of life and type III has slower clinical course
characterized by neurologic deterioration, myoclonus and demention. Although enzyme
replacement therapy is highly effective in treating visceral and hematologic
manifestations of the disease, it does not change neurological outcome. Hematopoietic
stem cell transplantation is also most likely ineffective in preventing neurological
disease. Therefore, new therapeutic strategies, such as intrathecal enzyme
replacement therapy and chaperone therapy, are beeing developed.
In our Department we are treating and following two siblings with type III Gaucher
disease. First patient, a girl, developed hepatosplenomegaly in the third year of life. As
she had total cavopulmonary anasthomosis due to tricuspid atresia type IB, at first it
was considered to be consequence of haemodynamic changes. Only after the latter
had been excluded it was suspected that she suffers from Gaucher disease and the
diagnosis was confirmed at the age of 4.5 years. At that point she had massive
hepatosplenomegaly, strabismus, oculomotor apraxia, dysarthria, stridor, ataxia and
seizures. In her younger brother the diagnosis was confirmed shortly after birth.
Clinically, he had no signs of neurological involvement and only mild splenomegaly. In
both children we started enzyme replacement therapy in order to reverse visceral
manifestations and chaperone therapy (small molecule used as mucolytic agent) in
order to stop neurologic deterioration in the older child and prevent or at least delay
neurologic symptoms in the younger one. Three months after combined therapy was
started residual glucocerebrosidase activity in skin fibroblast cell line was higher and
chitotriosidase activity in cerebrospinal fluid decreased. In addition, there seems to be
clinical improvement.
(this document arises from the project “InNerMeD-I-Network” which has received funding from the
European Union, in the framework of the Health Programme; also supported by grant 108-1081870-1885
of the Ministry of Science, Education and Sports, Republic of Croatia )
Za objavu naših radova dogovorili smo se za publiciranje u časopisu Paediatria
Croatica:
Radovi bi bili publicirani u redovnom broju Paediatria Croatica u 2014.
27
Uvjeti objavljivanja radova 42. Simpozija HDDB i Sastanka sekcije za bolesti
metabolizma HPD u redovnom broju Paediatria Croatica: najmanje 12 radova in
extenso, od toga 5 izvornih znanstvenih članka. Ostali radovi mogu biti sažeci.
Potrebno je da radovi stignu na naše e-mail adrese do 31. siječnja 2014. Nakon toga
se radovi upućuju recenzentima.
Upute za pisanje rada u Paediatria Croatica mogu se naći: www.paedcro.com
(odabrati stranicu: smjernice za autore)
Articles will be published in a regular number of the journal Paediatria Croatica
in 2014.
Conditions for publication in a regular number of the journal Paediatria Croatica
in 2014 dedicated to the 42nd Symposium of the Croatian Pediatric Neurology
Society and Meeting of the Association for Metabolic diseases of the Croatian
Pediatric Society: 12 articles, 5 must be scientific articles.
It is necessary that articles arrive to our e-mail address till the 31th January
2014. Then articles will be sent to reviewers.
Instructions for manuscript submission can be find at www.paedcro.com and
Guidelines for authors.
Dubravko Lapaine
Biography
Croatian - based didgeridoo
musician and composer one of the most revered
didgeridoo performers in
the world.
http://www.lapaine.com/epk/
28
Since 2000, he has been developing new ways of playing this ancient instrument and
released a range of audio works (solo albums, tracks for films and animations, music for theater
and dance performances) and received international musical awards (World of Music Awards
2009-finalist).
He has been described as "wizard who crams sounds of wind", "almost an
oracle" and "actor of a monodrama of vibrations" which serves to show Lapaine's focus on
exploring endless possibilities of yet uncharted didgeridoo sound world. His desire to explore
the potential deep sound of this most basic of instruments led him to stretch and distort the
basic natural design into a multitude of shapes and dimensions (reaching a length of 10m and
frequency of 20Hz) resulting in his own unique utterly absorbing performance.
Lapaine's way of playing is characterized by strong physicality and innumerable breaths of
perfect precision and speed counterbalanced by melodious voice. This creates a sense of vast
space and pulsing density in perfect harmony. Movements of breath, diaphragm, voice and lips
blend in the didgeridoo into a strange invisible and powerful earth music orchestra. The music
he produces out of various 'wooden tubes' seems to the listener as if coming from a deep
unknown origin letting us catch subtle melodies of wind intertwined with rhythmic
rumbling of the earth.
It is really with the live stage performance that Du's devotion to music comes to full
expression. Using odd Balkan rhythms as inspiration, he has developed his own notion of
rhythm that can grow into any measure creating compositions with melody and a richness of
sound. Combining this with gestures, stories, and poems the audience is literally grabbed and
carried on a journey into and through his own internal fantasy worlds. Dubravko typically uses
up to ten different instruments during his performances, each having its own musical story.
Dubravko is also actively working with a trio Druyd featuring didgeridoo, guitar and female
vocals.
NOTABLE PAST EVENTS
*Opening ceremony of the World Handball Championship in Split, Croatia (January 2009)
*Le Reve de Aborigenes Festival in Airvault, France (July 2009)
*RhythmTree Festival on Isle of Wight, UK (August 2009, 2010)
*Swiss Didge Weekend in Wiedlisbach, Switzerland (July 2009)
*Opening ceremony of Dubrovnik Summer Games @ Dubrovnik, Croatia (July 2008)
*Didjin'Oz 2008 in Forlimpopoli, Italy (November 2008, 2010)
*Didgeridoo/acrobatic show @ 4th Festival of New Circus, Zagreb (2007)
DISCOGRAPHY
KOSMOPTERIX - Album released in July 2009.
Rated second best Croatian ethno album 1n 2009 (Croatian Internet Music Magazine
glas.ba) http://music.lapaine.com/album/kosmopterix
IZ DUBINA BESVJESNIH - Self-released, arranged and produced album in 2008.
DRONAS / by Druyd - Album released in July 2010.
Debut album of Druyd, didgeridoo-guitar-female vocals trio.
http://music.druydmusic.com/album/dronas
DONATORI
PLIVA HRVATSKA d.o.o., Prilaz baruna Filipovića 25., 10000 Zagreb
Tel. + 385 1 372 0000; Faks: + 385 1 37 20 111; Email: [email protected]
Sanofi aventis Croatia d.o.o., Genzyme and Sanofi company, Heinzelova 70/II,10 000
Zagreb, Tel: 01/6003470; Fax: 01/6003480; www.genzyme.com
G-M Pharma Zagreb d.o.o.,Nutricia; Velika cesta 74, 10020 Zagreb
Tel:+3851 6234 053; Fax +3851 6260 667; www.g-m-pharma.hr
29
Otto Bock Adria d.o.o., Dr. Franje Tuđmana 14, 10431 Sveta Nedjelja
Tel:+3851 3361 544; Fax +3851 3365 986; Email:[email protected]
Nestle Adriatic d.o.o., Avenija Većeslava Holjevca 40, 10010 Zagreb
Tel. +3851 6328 000; Fax +3851 6328 099; Email:[email protected]
Vivera d.o.o., XIII Podbrežje 26, 10020 Zagreb
Tel. +3851 6593 790; Fax +3851 6593 798; Email:[email protected]
Belupo, lijekovi i kozmetika, d.d.,I. Savica 36, P.P.62, 10000 Zagreb
Tel.+3851 2481225;Fax +3851 2371370; Email: [email protected]
Commodatio d.o.o., Savjetovanje i posredovanje u marketingu, prodaji lijekova i medicinskih
proizvoda, Buzinski prilaz 10, 10010 Zagreb
Tel: +385 1 5790930, Fax +385 1 5790931, E-mail [email protected]
30

„POGLED U BUDUĆNOST: DRUŠTVENI MEDIJI – BUDUĆNOST

„Zajednice - prijatelji djece“

Ideje za paketiće:

Pismo HPD-a ministru - Hrvatsko pedijatrijsko društvo

Privremena lista za financiranje_prioritetno područje 1.2.1

CILJ NAM JE: TAJNA MOĆI JE U TRAŽENJU

Bilten - North West Balkans | Save the Children

Pregled

“MALA SIRENA” – IGRAONICA ZA

o kongresu u požegi

UDC 616.89 SPSIDE 39 (4) 193–260 (2011) ISSN 0303

BIOMEDICINSKA ISTRAŽIVANJA Karakteristike metaboličkog