CASE REPORT
A Case Report of Obsessive-Compulsive Disorder
Following Acute Disseminated Encephalomyelitis
AUTHORS: Katherine E. Muir, MD,a Katherine S. McKenney,
PhD,b Mary B. Connolly, MD,a and S. Evelyn Stewart, MDb
abstract
aDivision
We present a case of a boy who developed obsessive-compulsive
disorder (OCD) shortly after an episode of acute disseminated encephalomyelitis (ADEM). To our knowledge, this is the first report of
the development of OCD in a child who has had ADEM. This presentation is consistent with our understanding of OCD as a complex
genetic disease involving the cerebral white matter tracts, and may
indicate a potential pathway for the development of OCD in genetically
vulnerable individuals or a shared trigger for the development of
pediatric acute-onset neuropsychiatric syndrome and ADEM. Pediatrics 2013;132:e1–e4
of Pediatric Neurology, Department of Pediatrics;
of Psychiatry; University of British Columbia; and
bDivision of Psychiatry, B.C. Children’s Hospital, Vancouver, British
Columbia, Canada
cDepartment
KEY WORDS
obsessive-compulsive disorder, demyelinating diseases,
pediatrics
ABBREVIATIONS
ADEM—acute disseminated encephalomyelitis
CSF—cerebrospinal fluid
OCD—obsessive-compulsive disorder
PANS—pediatric acute-onset neuropsychiatric syndrome
Dr Muir conceptualized the case report and wrote the initial
manuscript; Dr McKenney conducted the detailed psychiatric
history; Dr Connolly is this patient’s neurologist from initial
diagnosis and contributed the neurologic data and critically
reviewed and revised the manuscript; Dr Stewart
conceptualized the case report and critically reviewed and
revised the manuscript; and all authors approved the final
manuscript as submitted.
www.pediatrics.org/cgi/doi/10.1542/peds.2012-2876
doi:10.1542/peds.2012-2876
Accepted for publication May 10, 2013
Address correspondence to S. Evelyn Stewart, MD, Pediatric OCD
Program, A3-118 938 West 28th Ave, Vancouver BC, V5Z 4H4.
E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2013 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
FUNDING: This project was conducted with assistance from
a Michael Smith Foundation Health Research award to Dr
Stewart.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated
they have no potential conflicts of interest to disclose.
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e1
There is an increasing body of literature
implicating structural white matter
abnormalities in obsessive-compulsive
disorder (OCD). Diffusion tensor imaging studies in OCD-affected adults1–3
and children4 have demonstrated
white matter composition abnormalities, albeit with some variability of
findings. Candidate gene studies have
implicated genes involved in both the
development and structural integrity of
the myelin sheath.5,6 Moreover, a growing body of research provides evidence
that OCD is a complex genetic disorder
in which both inborn genetic vulnerability and environmental factors play
important etiologic roles.7
The variability of OCD neuroimaging
findings may be at least partially
accounted for by the fact that this is
a phenotypically heterogeneous disorder.8 A recent imaging study has demonstrated that different symptom
dimensions within OCD may be associated with distinct neural networks.9 It
is likely that the etiology of OCD is also
multifactorial. The new clinical criteria
developed for pediatric acute-onset
neuropsychiatric syndrome (PANS)10
address some of this etiologic heterogeneity by defining a distinct group of
children who have an abrupt onset of
OCD after either an infectious trigger
or an environmental trigger.
Acute disseminated encephalomyelitis
(ADEM) is a disorder that shares some
similar features with PANS. Consensus
definition11 describes ADEM as a clinical event of presumed inflammatory or
demyelinating etiology with acute or
subacute onset that affects multiple
areas of the central nervous system.
Patients have encephalopathy, variable neurologic deficits, and MRI features compatible with inflammatory
demyelination.
Here we describe a case that, to the best
of our knowledge, is the first report of
subacute-onset OCD in a child with
ADEM.
e2
CASE REPORT
A 12-year-old boy was referred to a pediatric OCD subspecialty clinic for
evaluation of obsessive compulsive
symptoms. He was born after an uncomplicated pregnancy at full term. He
was delivered via forceps due to fetal
distress and a nuchal cord. He was
initially cyanosed but did not require
resuscitation or demonstrate symptoms of neurologic dysfunction. He was
developmentally normal except for mild
fine motor and articulation difficulties
and advanced language skills. There
were no notable concerns related to
attention, behavior, anxiety, mood, or
learning previous to the illness described below. With respect to family
history, a maternal great uncle and the
maternal grandmother had OCD, both
parents had reading difficulties, a maternal cousin had schizophrenia, and
a paternal grandfather had bipolar
disorder.
At 6 years of age, he presented with
diplopia, headache, irritability, lethargy,
and sleep disturbance that was preceded by a 2-week history of conjunctivitis and pain and joint swelling,
diagnosed as postinfectious arthritis.
The neurologic examination at presentation demonstrated an altered
level of consciousness with alternating
drowsiness and irritability, bilateral
sixth nerve palsies, and bilateral papilledema. He was afebrile and the systemic examination was normal.
MRI of the brain initially showed no
abnormalities. At lumbar puncture, the
opening pressure of cerebrospinal fluid
(CSF) was elevated at 45 cm H2O. CSF
examination showed 31 white blood
cells (82% lymphocytes), 16 red blood
cells, protein 0.46 g/L, glucose 2.8
mmol/L, and lactate 1.3 mmol/L. Gram
stain and culture of CSF were negative.
An extensive infectious and rheumatologic work-up was negative. Repeat
brain MRI 1 month later demonstrated
an area of increased T2-weighted signal
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in the white matter of the left frontal
lobe near the genu of the corpus callosum and a smaller area of increased
T2 signal in the white matter of the
right frontal lobe (Fig 1). There was no
enhancement with gadolinium.
A diagnosis of ADEM was made, he was
treatedwithhigh-dosemethylprednisone,
and his neurologic symptoms resolved. An MRI 1 year later showed that
the white matter lesions were both
smaller.
This patient was closely followed neurologically and had no recurrence of
symptoms indicating demyelination.
After his illness, he had poor attention,
distractibility, and worsening of his fine
motor difficulties. Neuropsychological
testing performed 8 months after diagnosis using the Wechsler Intelligence
Scale for Children, 4th edition, demonstrated average intellectual function
overall, but with coding and symbol
search subtests and processing speed
index on the second percentile. The
Wechsler Individual Achievement test,
2nd edition, identified below average
scores in word reading, reading comprehension, math reasoning, and spelling. The Behavior Rating Inventory of
Executive Function revealed more executive problems. His language and
visual spatial skills were in the average
range, but fine motor skills using the
Purdue Pegboard were reduced. Given
the absence of cognitive difficulties
before his illness, no formal baseline
neuropsychological testing results are
available for comparison.
Follow-up neuropsychological evaluation at the age of 10 years revealed
improved overall intellectual function,
increasing to the 63rd percentile from
the 32nd percentile. However, he had
significant persisting deficits in processing speed and working memory.
Academically, he continued to meet diagnostic criteria for a mathematics
learning disorder. He had intermittent
motor tics and also met clinical criteria
CASE REPORT
criteria for OCD after an episode of
ADEM raises important questions about
the etiology of both of these disorders.
FIGURE 1
T2-weighted cranial MRI, axial slices. A, Normal MRIs of the frontal lobes on initial MRI. B, Arrows indicate
areas of T2 hyperintensity in the left and right frontal lobes 1 month after presentation. C, Arrows indicate
decreased size of T2 hyperintense areas at 1 year follow-up.
for diagnoses of generalized anxiety
disorder and attention deficit hyperactivity disorder.
In addition to the above, the patient
experienced a subacute onset of OCD
symptoms within 1 month of being
hospitalized for ADEM. At that time, the
school expressed concern that he was
spending excessive time washing his
hands. He expressed a fear of germs
and becoming sick, which was decreased by hand-washing. The OCD
symptoms continued for 2 months, then
decreased somewhat and waxed and
waned until 11 years of age, when they
worsened significantly. His contamination fears, focused on contracting
a serious illness such as Salmonella,
led to food intake restriction at school
and contributed to a 30-pound weight
loss. He re-engaged in excessive hand
washing, doing so up to 18 times daily,
which resulted in skin irritation and
chronic redness. Moreover, he did not
want to swallow his saliva.
At the time of initial assessment for OCD,
the patient presented as a cooperative
12-year-old. He was casually dressed
and there were no noted movement
abnormalities. His speech was normal
in rate and rhythm, and mood was
somewhat anxious with a congruent
affect. His thought content was notable
for obsessions. He had difficulty in
maintaining attention throughout the
assessment. On the Children’s YaleBrown Obsessive Compulsive Scale,
he scored in the moderate range with
scores of 8/20 for obsessions and 14/20
for compulsions for a total score of
22/40. This patient was started on a
selective serotonin reuptake inhibitor
and scheduled for cognitive behavioral
therapy, the 2 evidence-based therapies
for children with OCD.12,13 Currently,
his obsessive compulsive symptoms
are significantly improved on sertraline and by using cognitive behavioral
strategies.
This presentation of new-onset obsessive compulsive symptoms meeting
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It is possible that the findings observed
in our patient are an example of a previously unreported pathophysiologic
pathway to developing OCD. This is
consistent with current research demonstrating structural white matter
changes in patients with OCD. The etiology of white matter changes is likely to
be multifactorial, with evidence from
a recent twin study finding that different
white matter abnormality regions are
associated with environmental versus
genetic risk loading for obsessive
compulsive symptoms.14 This patient
had neuroimaging findings demonstrating focal white matter changes in
his anterior frontal lobes, regions that
have been implicated in OCD in the
orbitofrontal striatal model.15
This patient’s symptom presentation
provides suggestive evidence that demyelinating injury may lead to the development of OCD. This theory is
supported by an additional line of research, in which increased OCD risk
has been reported in patients with
multiple sclerosis,16,17 another disorder involving demyelination. A recent
Canadian study estimated the lifetime
prevalence of OCD in patients with
multiple sclerosis to be 8.6%,18 which is
significantly higher than general population lifetime prevalence rates of 1%
to 2%.19
It is also possible that this presentation
satisfies diagnostic criteria for PANS.
The family gave a history of a subacute
rather than an abrupt onset of symptoms, given that the OCD symptoms
were not noticed during hospitalization.
To fulfill the diagnostic criteria for
PANS,10 there should be an abrupt,
dramatic onset of symptoms. There
should also be concurrent presence of
additional neuropsychiatric symptoms.
The patient’s school difficulties and
behavioral changes such as being
e3
irritable and easily frustrated could
satisfy this second criterion, however
these features are also commonly seen
in patients after ADEM. If this is a case
of PANS, it would seem that PANS and
ADEM had a unitary trigger in this patient. Because both PANS and ADEM are
presumed to have a precipitant causing the patient to develop psychiatric
or neurologic symptoms, it is possible
that similar environmental, or, as in
this case, infectious triggers could
produce these similar phenomena.
Despite the suggestive evidence that
ADEM and OCD onset were not independently occurring events for this
patient, there are alternate explanations that require consideration. This
patient has a family history of OCD, thus
increasing his vulnerability to OCD. It is
possible that this patient’s OCD is unrelated to the ADEM episode and is
simply due to his genetic predisposition, given the heritability estimates of 45% to 65% for the child-onset
form of the disorder.20 However, it more
likely supports the model of OCD as
a complex genetic disorder in which an
environmental trigger, in the context of
genetic vulnerability, results in the onset of illness.
8. Stewart SE, Rosario MC, Brown TA, et al.
Principal components analysis of obsessivecompulsive disorder symptoms in children
and adolescents. Biol Psychiatry. 2007;61(3):
285–291
9. van den Heuvel OA, Remijnse PL, Mataix-Cols
D, et al. The major symptom dimensions of
obsessive-compulsive disorder are mediated by partially distinct neural systems.
Brain. 2009;132(pt 4):853–868
10. Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome:
modifying the PANDAS criteria to describe
PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Ther. 2012;2(2).
11. Krupp LB, Banwell B, Tenembaum S; International Pediatric MS Study Group.
Consensus definitions proposed for pediatric multiple sclerosis and related disorders.
Neurology. 2007;68(16 suppl 2):S7–S12
12. Geller DA, Biederman J, Stewart SE, et al.
Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessivecompulsive disorder. Am J Psychiatry.
2003;160(11):1919–1928
13. Freeman JB, Choate-Summers ML, Moore
PS, et al. Cognitive behavioral treatment for
young children with obsessive-compulsive
disorder. Biol Psychiatry. 2007;61(3):337–343
14. den Braber A, van ’t Ent D, Boomsma DI,
et al. White matter differences in monozygotic twins discordant or concordant for
obsessive-compulsive symptoms: a combined
diffusion tensor imaging/voxel-based morphometry study. Biol Psychiatry. 2011;70
(10):969–977
Menzies L, Chamberlain SR, Laird AR,
Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and
neuropsychological studies of obsessivecompulsive disorder: the orbitofrontostriatal model revisited. Neurosci Biobehav
Rev. 2008;32(3):525–549
Miguel EC, Stein MC, Rauch SL, O’Sullivan
RL, Stern TA, Jenike MA. Obsessivecompulsive disorder in patients with multiple sclerosis. J Neuropsychiatry Clin
Neurosci. 1995;7(4):507–510
George MS, Kellner CH, Fossey MD.
Obsessive-compulsive symptoms in a patient with multiple sclerosis. J Nerv Ment
Dis. 1989;177(5):304–305
Korostil M, Feinstein A. Anxiety disorders and
their clinical correlates in multiple sclerosis
patients. Mult Scler. 2007;13(1):67–72
Weissman MM, Bland RC, Canino GJ, et al;
The Cross National Collaborative Group.
The cross national epidemiology of obsessive compulsive disorder. J Clin Psychiatry.
1994;55(suppl):5–10
van Grootheest DS, Cath DC, Beekman AT,
Boomsma DI. Twin studies on obsessivecompulsive disorder: a review. Twin Res
Hum Genet. 2005;8(5):450–458
This case is important because it is
the first report of OCD occurring after
ADEM. This presentation is consistent
with our understanding of OCD as
a disease involving the frontal cortical white matter tracts and may indicate a potential pathway for the
development of OCD or a shared trigger for the development of PANS and
ADEM.
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e4
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15.
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20.
A Case Report of Obsessive-Compulsive Disorder Following Acute Disseminated
Encephalomyelitis
Katherine E. Muir, Katherine S. McKenney, Mary B. Connolly and S. Evelyn Stewart
Pediatrics; originally published online August 5, 2013;
DOI: 10.1542/peds.2012-2876
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from by guest on June 17, 2017
A Case Report of Obsessive-Compulsive Disorder Following Acute Disseminated
Encephalomyelitis
Katherine E. Muir, Katherine S. McKenney, Mary B. Connolly and S. Evelyn Stewart
Pediatrics; originally published online August 5, 2013;
DOI: 10.1542/peds.2012-2876
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/early/2013/07/31/peds.2012-2876
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from by guest on June 17, 2017