Evaluating the Current State of Epilepsy Care in the Province of Ontario.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Referral practices for epilepsy surgery in pediatric patients: A North American Study.

OBJECTIVE: Patients with epilepsy who do not respond to two trials of appropriate antiepileptic drugs are considered to have drug-resistant epilepsy (DRE). The International League Against Epilepsy recommends patients with DRE be referred for surgical evaluation; however, prior literature suggests this is an underutilized intervention, especially in the pediatric setting. This study captures practices of North American pediatric neurologists regarding the management of DRE and factors that may promote or limit referrals for epilepsy surgical evaluation. METHODS: A REDCap survey was distributed via the Child Neurology Society mailing list to pediatric neurologists practicing in North America. Ethics approval from the Children's Hospital of Eastern Ontario Research Ethics Board was granted prior to the start of data collection. RESULTS: Ninety-eight responses were included in the analysis; 77% of participants currently practice in the United States; 73.5% of respondents reported they would refer a patient for surgical consultation after two failed medications. Of all potential predictors tested in a binary logistic regression model, only annual referral volume predicted whether participants refer patients after three or more failed medications. Centers with high referral volume were 37% more likely to adhere to the guideline of referral after two failed medications. SIGNIFICANCE: Pediatric neurologists demonstrate fair knowledge of formal recommendations to refer patients for surgical evaluation after two failed medication trials, although referral rates remain unacceptably low. Participants continue to report that they would not refer patients with generalized electroencephalographic findings for surgical evaluation; this should continue to be addressed. Other modifiable factors reported, especially family perceptions of epilepsy surgery, should be prioritized when developing tools to enhance effective referrals and increase utilization of epilepsy surgery in the management of pediatric DRE.

Implementation of Epilepsy Multigene Panel Testing in Ontario, Canada.

BACKGROUND: Epilepsy is a common neurological condition that shows a marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical genetic testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available for epilepsy as a licensed clinical diagnostic test in Ontario, Canada. Eligible patient samples are sent out of country for testing by commercial laboratories, which incurs significant cost to the public healthcare system. OBJECTIVE: An expert Working Group of medical geneticists, pediatric neurologists/epileptologists, biochemical geneticists, and clinical molecular geneticists from Ontario was formed by the Laboratories and Genetics Branch of the Ontario Ministry of Health and Long-Term Care to develop a programmatic approach to implementing epilepsy panel testing as a provincial service. RESULTS: The Working Group made several recommendations for testing to support the clinical delivery of care in Ontario. First, an extension of community healthcare outcomes-based program should be incorporated to inform and educate ordering providers when requesting and interpreting a genetic panel test. Second, any gene panel testing must be "evidence-based" and takes into account varied clinical indications to reduce the chance of uncertain and secondary results. Finally, an ongoing evaluative process was recommended to ensure continued test improvement for the future. CONCLUSION: This epilepsy panel testing implementation plan will be a model for genetic care directed toward a specific set of conditions in the province and serve as a prototype for genetic testing for other genetically heterogeneous diseases.

Mise en œuvre d'un test diagnostique permettant en Ontario l'analyse d'un panel de plusieurs gènes liés à l'épilepsie.Contexte:L'épilepsie demeure un trouble neurologique fréquent dont la prédisposition génétique apparaît notable. L'émergence du séquençage de nouvelle génération (SNG) a aussi transformé les tests génétiques en permettant un dépistage rapide des variantes causales que l'on retrouve dans de nombreux gènes. À l'heure actuelle, il n'existe pas, pour l'épilepsie, de tests diagnostiques homologués qui permettent en Ontario l'analyse d'un panel de gènes en vertu du SNG. Les échantillons de patients admissibles sont alors envoyés à l'extérieur du Canada afin d'être analysés par des laboratoires commerciaux, ce qui pèse lourd dans les budgets des systèmes publics de santé. Objectif : Un groupe de travail formé d'experts (généticiens médicaux, neurologues pédiatriques et spécialistes en épileptologie, généticiens biochimiques et généticiens moléculaires cliniques) a été formé par le service des laboratoires et de la génétique des ministères de la Santé et des Soins de Longue durée de l'Ontario afin d'élaborer une démarche programmatique visant à mettre en œuvre des tests diagnostiques basés sur un panel de plusieurs gènes. Ces tests seraient ensuite reconnus à titre de service public. Résultats:En matière de dépistage, ce groupe de travail a ainsi émis plusieurs recommandations visant à accompagner la prestation clinique en Ontario. Tout d'abord, un programme s'inspirant du projet « ECHO ¼ (Extension of Community Healthcare Outcomes) devrait être ajouté dans le but de renseigner et de sensibiliser les prestataires de soins de santé qui demandent et qui interprètent ces tests basés sur un panel de plusieurs gènes. Ensuite, tout test de ce type doit reposer sur des preuves et tenir compte d'une panoplie d'indications cliniques afin de réduire les possibilités d'incertitude et de résultats secondaires. Enfin, il a été recommandé de procéder à un processus continu d'évaluation pour s'assurer que ces tests puissent être améliorés dans le futur. Conclusion:Ce plan de mise en œuvre de tests basés sur un panel de plusieurs gènes deviendra un modèle pour les soins destinés à un ensemble spécifique de problèmes de santé en Ontario. Outre l'épilepsie, il pourra servir comme prototype pour le dépistage d'autres maladies hétérogènes sur le plan génétique.

Molecular epidemiological study on Infectious Pancreatic Necrosis Virus isolates from aquafarms in Scotland over three decades.

In order to obtain an insight into genomic changes and associated evolution and adaptation of Infectious Pancreatic Necrosis Virus (IPNV), the complete coding genomes of 57 IPNV isolates collected from Scottish aquafarms from 1982 to 2014 were sequenced and analysed. Phylogenetic analysis of the sequenced IPNV strains showed separate clustering of genogroups I, II, III and V. IPNV isolates with genetic reassortment of segment A/B of genogroup III/II were determined. About 59 % of the IPNV isolates belonged to the persistent type and 32 % to the low-virulent type, and only one highly pathogenic strain (1.79 %) was identified. Codon adaptation index calculations indicated that the IPNV major capsid protein VP2 has adapted to its salmonid host. Under-representation of CpG dinucleotides in the IPNV genome to minimize detection by the innate immunity receptors, and observed positive selection in the virulence determination sites of VP2 embedded in the variable region of the main antigenic region, suggest an immune escape mechanism driving virulence evolution. The prevalence of mostly persistent genotypes, together with the assumption of adaptation and immune escape, indicates that IPNV is evolving with the host.

Pathogenesis of experimental salmonid alphavirus infection in vivo: an ultrastructural insight.

Salmonid alphavirus (SAV) is an enveloped, single-stranded, positive sense RNA virus belonging to the family Togaviridae. It causes economically devastating disease in cultured salmonids. The characteristic features of SAV infection include severe histopathological changes in the heart, pancreas and skeletal muscles of diseased fish. Although the presence of virus has been reported in a wider range of tissues, the mechanisms responsible for viral tissue tropism and for lesion development during the disease are not clearly described or understood. Previously, we have described membrane-dependent morphogenesis of SAV and associated apoptosis-mediated cell death in vitro. The aims of the present study were to explore ultrastructural changes associated with SAV infection in vivo. Cytolytic changes were observed in heart, but not in gill and head-kidney of virus-infected fish, although they still exhibited signs of SAV morphogenesis. Ultrastructural changes associated with virus replication were also noted in leukocytes in the head kidney of virus-infected fish. These results further describe the presence of degenerative lesions in the heart as expected, but not in the gills and in the kidney.

Cubilin and amnionless mediate protein reabsorption in Drosophila nephrocytes.

The insect nephrocyte and the mammalian glomerular podocyte are similar with regard to filtration, but it remains unclear whether there is an organ or cell type in flies that reabsorbs proteins. Here, we show that the Drosophila nephrocyte has molecular, structural, and functional similarities to the renal proximal tubule cell. We screened for genes required for nephrocyte function and identified two Drosophila genes encoding orthologs of mammalian cubilin and amnionless (AMN), two major receptors for protein reabsorption in the proximal tubule. In Drosophila, expression of dCubilin and dAMN is specific to nephrocytes, where they function as co-receptors for protein uptake. Targeted expression of human AMN in Drosophila nephrocytes was sufficient to rescue defective protein uptake induced by dAMN knockdown, suggesting evolutionary conservation of Cubilin/AMN co-receptors function from flies to humans. Furthermore, we found that Cubilin/AMN-mediated protein reabsorption is required for the maintenance of nephrocyte ultrastructure and fly survival under conditions of toxic stress. In conclusion, the insect nephrocyte combines filtration with protein reabsorption, using evolutionarily conserved genes and subcellular structures, suggesting that it can serve as a simplified model for both podocytes and the renal proximal tubule.

Congenital tremor and myopathy secondary to novel MYBPC1 variant.

Congenital myopathy with tremor (MYOTREM) is a recently described disorder characterized by mild myopathy and a postural and intention tremor present since early infancy. MYOTREM is associated with pathogenic variants in MYBPC1 which encodes slow myosin-binding protein C, a sarcomere protein with regulatory and structural roles. Here, we describe a family with three generations of variably affected members exhibiting a novel variant in MYBPC1 (c.656 T > C, p.Leu219Pro). Among the unique features of affected family members is the persistence of tremor in sleep. We also present the first muscle magnetic resonance images for this disorder, and report muscle atrophy and fatty infiltration.

Stress responses of adolescent male and female rats exposed repeatedly to cat odor stimuli, and long-term enhancement of adult defensive behaviors.

In order to characterize the short- and long-term effects of repeated stressor exposure during adolescence, and to compare the effects of using two sources of cat odor as stressor stimuli, male and female adolescent rats (postnatal day (PND) ∼ 38-46) were exposed on five occasions to either a control stimulus, a cloth stimulus containing cat hair/dander, or a section of cat collar previously worn by a cat. Relative to control stimulus exposure, activity was suppressed and defensive behavior enhanced during exposure to either cat odor stimulus (most pervasively in rats exposed to the collar). Only cloth-exposed rats showed elevated levels of corticosterone (CORT), and only after repeated stressor exposure, but interestingly, rats exposed to the collar stimulus during adolescence continued to show increased behavioral indices of anxiety in adulthood. In this group, the time an individual spent in physical contact with a cagemate during the final adolescent exposure was negatively related to stress-induced CORT output in adulthood, which suggests that greater use of social support during adolescent stress may facilitate adult behavioral coping, without necessitating increased CORT release. These findings demonstrate that adolescent male and female rats respond defensively to cat odor stimuli across repeated exposures and that exposure to such stressors during adolescence can augment adult anxiety-like behavior in similar stressful conditions. These findings also suggest a potential role for social behavior during adolescent stressor exposure in mediating long-term outcomes.

Enhanced stress responses in adolescent versus adult rats exposed to cues of predation threat, and peer interaction as a predictor of adult defensiveness.

Development of the hypothalamic-pituitary-adrenal (HPA) axis is influenced by external factors during early life in mammals, which optimizes adult function for predicted conditions. We have hypothesized that adolescence represents a sensitive period for the development of some aspects of adult stress response regulation. This was based on prior work showing that repeated exposure of rats to a stressor across an adolescent period increases fearfulness in a novel environment in adulthood and results in lower levels of dopamine receptor subtype-2 protein in prefrontal cortex. Here, we further our investigation of both acute and long-term effects of repeated adolescent stressor exposure on physiological (i.e., corticosterone) and behavioral (i.e., defensive behavior) measures of stress responding in male and female rats. Furthermore, we compared outcomes with those following identical manipulations administered in early adulthood and found that animals exposed to cues of predation threat during adolescence showed the most robust defensive responses to a homotypic stressor encountered in adulthood. Peer interaction during control manipulation in adolescence was identified as an important individual characteristic mediating development of adult defensive strategies.

Childhood aggression, callous-unemotional traits and oxytocin genes.

Given the known behavior effects of oxytocin,and in particular its putative effect on trust, affiliation and anxiety, we hypothesized that oxytocin may be involved in the development and expression of callous-unemotional traits in children with aggressive antisocial behavior. We recruited 162 children between the ages of 6 and 16. The majority of subjects were Caucasian (84.0%) compared to African-Canadian (4.9%) and others (11.1%). The oxytocin and oxytocin receptor gene polymorphisms were genotyped and analyzed for possible association with child aggression in a case­control study design as well as with callous-unemotional traits in a within cases analysis. We did not have significant findings with our tested OXTR markers in the case­control analysis. We found the OXTR_rs237885 AA genotype carriers to score higher than AC or CC genotype carriers on the callous-unemotional traits. This result remained significant following correction for multiple testing. No other markers were found to be significant. However, the haplotype consisting of the OXTR_rs237885 A allele and OXTR_rs2268493 A allele was associated with significantly higher callous-unemotionals cores than other haplotypes. This is the first known study to show a significant association between callous unemotional traits in children and adolescents with extreme, persistent pervasive aggression and a polymorphism on the oxytocin receptor. Given the small sample size and the possibility of false positive effects, the need to replicate and verify these findings is required.

Isolation of a New Infectious Pancreatic Necrosis Virus (IPNV) Variant from a Fish Farm in Scotland.

The aquatic virus, infectious pancreatic necrosis virus (IPNV), is known to infect various farmed fish, in particular salmonids, and is responsible for large economic losses in the aquaculture industry. Common practices to detect the virus include qPCR tests based on specific primers and serum neutralization tests for virus serotyping. Following the potential presence of IPNV viruses in a fish farm in Scotland containing vaccinated and IPNV-resistant fish, the common serotyping of the IPNV isolates was not made possible. This led us to determine the complete genome of the new IPNV isolates in order to investigate the cause of the serotyping discrepancy. Next-generation sequencing using the Illumina technology along with the sequence-independent single primer amplification (SISPA) approach was conducted to fully characterize the new Scottish isolates. With this approach, the full genome of two isolates, V1810-4 and V1810-6, was determined and analyzed. The potential origin of the virus isolates was investigated by phylogenetic analyses along with tridimensional and secondary protein structure analyses. These revealed the emergence of a new variant from one of the main virus serotypes, probably caused by the presence of selective pressure exerted by the vaccinated IPNV-resistant farmed fish.

High-dose steroid and heparin: a novel therapy for cerebral vasculitis associated with presumed group A Streptococcus meningitis.

Cerebral vasculitis is a serious complication of bacterial meningitis that can cause significant morbidity and mortality due to stroke. Currently, there are no treatment guidelines or safety and efficacy studies on the management of cerebral vasculitis in this context. Herein, we report a case of a previously well 11-year-old girl who presented with acute otitis media that progressed to mastoiditis and fulminant meningitis. Group A Streptococcus was found in blood and ear-fluid cultures (lumbar puncture was unsuccessful). Her decreased level of consciousness persisted despite appropriate antimicrobial treatment, and repeat MRI revealed extensive large vessel cerebral vasculitis. Based on expert opinion and a presumed inflammatory mechanism, her cerebral vasculitis was treated with 7 days of pulse intravenous methylprednisolone followed by oral prednisone taper. She was also treated with intravenous heparin. Following these therapies, she improved clinically and radiographically with no adverse events. She continues to undergo rehabilitation with improvement.

Tuberous sclerosis complex associated intracranial lesion found by antenatal ultrasound.

Tuberous sclerosis complex (TSC) is characterized by the growth of benign tumors in the skin, brain, kidneys, lung and heart [1]. Prognosis is mostly determined by the extent of brain involvement as tumors in the brain lead to seizures, cognitive impairment and behavioral problems. Current evidence suggests anti-epileptic treatment before the onset of seizures reduces epilepsy severity and risk of cognitive impairment in TSC however identifying these children prior to the onset of seizures is challenging. Our case shows retrospectively reviewed antenatal ultrasounds of a male child diagnosed postnatally at 12 days of life with TSC. Analysis found a soft tissue mass in the right ventricle on antenatal ultrasound which was not captured in the initial ultrasound report. Though there are no reports of sensitivity of neurosonography for the antenatal detection of intracranial abnormalities associated with TSC, our case suggests that antenatal ultrasound could be used as a screening modality for antenatal diagnosis of TSC.

Pattern of Brain Injury Predicts Long-Term Epilepsy Following Neonatal Encephalopathy.

OBJECTIVE: To determine if patterns of hypoxic-ischemic brain injury on magnetic resonance imaging (MRI) in term newborns predict subsequent childhood epilepsy. METHODS: This retrospective cohort study includes term newborns with encephalopathy (n = 181) born between 2004-2012 and admitted to British Columbia Children's Hospital. MRI was performed between 3 and 5 days of age. The predominant patterns of hypoxic-ischemic injury were classified as Normal, Watershed, Basal Nuclei, Total, and Focal-Multifocal. Lesions in hippocampus, motor and occipital cortex were noted. RESULTS: Of 181 newborns, 166 (92%) survived the neonatal period, and 132 (80%) had follow-up with a median duration of 61 months (IQR: 28-95). Twenty-three children (17%) developed epilepsy. A higher proportion with Watershed, Basal Nuclei, or Total patterns developed epilepsy (P < .001). Injury to motor cortex, hippocampus, and occipital lobe (P < .01) were independent risk factors for epilepsy. In the adjusting logistic model, Watershed (odds ratio = 16.0, 95% CI [1.3, 197.2], P = .03) and Basal Nuclei injury (odds ratio = 19.4, 95% CI [1.9, 196.3], P = .01) remained independent risk factors. Therapeutic hypothermia did not alter these associations. Severity of brain injury and recurrent neonatal seizures are other clinical risk factors. SIGNIFICANCE: In term newborns with hypoxic-ischemic encephalopathy, the predominant pattern of Watershed and Basal Nuclei injury are valuable predictors for development of epilepsy in later childhood.

Narcolepsy and Hypothalamic Region Tumors: Presentation and Evolution.

OBJECTIVE: Because most cases of brain tumor-associated narcolepsy have been published in the form of case reports or small series, the clinical presentation and evolution have not been well described. We sought to better define the epidemiology, etiology, and outcome of brain tumor-related narcolepsy. METHODS: We conducted an extensive review of the literature to identify cases of narcolepsy associated with brain tumors. Only cases of brain tumors involving the hypothalamic region including the suprasellar, sellar, and thalamus were included in this study. RESULTS: We report a child with possible narcolepsy in a child with a brain tumor. Through our literature review, we identified 25 additional cases of narcolepsy associated with brain tumors affecting the hypothalamic area. Most symptomatic narcolepsy cases were reported in children (70%). Half of the patients (13 of 25, 52%) developed narcolepsy after surgery, whereas 11 patients (44%) were symptomatic at the time of the tumor diagnosis. Ten patients had narcolepsy without cataplexy. Most cases were associated with craniopharyngioma (38%), adenoma (24%), and glioma (14%). Three, including our patient, experienced a complete resolution of symptoms. All patients underwent biopsy and were treated with adjuvant therapy. For patients with persistent symptoms, most (60%) improved following medical management of narcolepsy. CONCLUSION: This study represents the largest compilation of patients with this association. Our study allows us to better understand the etiology and outcome of patients with narcolepsy-related brain tumors.

Video Diversion Improves Success Rate of Fundoscopic Examination in Children: A Prospective Randomized Controlled Trial.

BACKGROUND: Fundoscopy is an important component of the neurological examination as it can detect pathologies such as high intracranial pressure. However, the examination can be challenging in young children. This study evaluated whether playing a video during eye examination improves the success, duration, and ease of pediatric fundoscopy. MATERIALS AND METHODS: This was a prospective, multipractitioner, multiclinic, randomized controlled trial. Patients aged one to four years were recruited in the emergency department, neurology clinic, spinal cord clinic, and general pediatric clinic. Eye examination was randomized to video or non-video-assisted fundoscopy. Successful examinations were defined as visualizing the fundus within 60 seconds. Time to visualize optic disc was recorded and difficulty of examination was assessed using a 10-point Likert scale. RESULTS: We recruited 101 subjects with a mean age of 2.8 years. Overall, there was a 20% absolute improvement in the success rate of visualizing the optic disc in the video versus non-video group (P < 0.001, 95%CI: 7.8% to 31%). Time to visualize optic disc was also improved (Δ5.3 seconds, P < 0.01, 95%CI: 1.4 to 9.1 seconds). Practitioners and caregivers noticed a 33% (P < 0.01, 95%CI: 21% to 44%) and 42% (P < 0.01, 95%CI: 30% to 56%) relative improvement in the ease of examination with video, respectively. CONCLUSIONS: The use of videos improved the ease, duration, and, most importantly, the success of fundoscopy in younger children. This simple, inexpensive adjunct has great potential to improve the ease and efficacy of this aspect of the neurological examination and allow fundoscopic examination to be effectively performed earlier in the age-appropriate vision screening protocols.

Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review.

BACKGROUND & AIMS: Nonselective non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 inhibitors (COX-2s) are used to treat a variety of arthritic and inflammatory conditions. The aim of this study was to assess the upper gastrointestinal (GI) harms of the long-term use of COX-2s, compared with nonselective NSAIDs and placebo, in arthritis sufferers. METHODS: A systematic review of randomized controlled trials (RCTs) was conducted. Searches were conducted in (1) Cochrane Central Register of Controlled Trials (CENTRAL), (2) the Cochrane Collaboration Library (2005), (3) MEDLINE (to December 2006), and (4) Excerpta Medica Database (EMBASE) (to June 2005). Reference lists from trials and abstracts of conference proceedings were searched by hand, and experts were contacted to identify further relevant trials. RCTs of celecoxib, rofecoxib, etoricoxib, valdecoxib, and lumiracoxib were included if they reported on endoscopic ulcers, clinically important ulcer complications, or adverse gastrointestinal (GI) symptoms with the use of these COX-2s, compared with placebo or with nonselective NSAIDs. Study selection and data extraction were performed in duplicate by independent reviewers. Data were analyzed by using Review Manager 4.2 in accordance with accepted meta-analysis techniques. RESULTS: Compared with nonselective NSAIDs, COX-2s produced significantly fewer gastroduodenal ulcers (relative risk, 0.26; 95% confidence interval, 0.23-0.30) and clinically important ulcer complications (relative risk, 0.39; 95% confidence interval, 0.31-0.50), as well as fewer treatment withdrawals caused by GI symptoms. The co-administration of acetylsalicylic acid appears to reduce the GI safety of COX-2s in subgroup analyses. CONCLUSIONS: COX-2s appear to offer greater upper GI safety and are better tolerated than nonselective NSAIDs. The co-administration of acetylsalicylic acid might reduce the safety advantage of COX-2s over that of nonselective NSAIDs.

Longitudinal Outcomes in the 2014 Acute Flaccid Paralysis Cluster in Canada.

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.

A case report of obsessive-compulsive disorder following acute disseminated encephalomyelitis.

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.