Background: Epileptic spasms (ES) are a devastating seizure type with poor neurodevelopmental outcome; 1/3 are resistant to treatment with first line therapies. Recently attention has been drawn to the ketogenic diet (KD) as a potentially effective therapy, though data regarding optimal time of initiation, and its sustained effectiveness, are lacking. Methods: Retrospective chart review of all patients with ES treated with KD at BC Children’s Hospital between 2002 and 2020 (n=28) with comparison of spasm response based on age of initiation of KD in two groups: < 12 months (n=11) and ≥ 12 months (n=17). Results: Comparing the <12 months and ≥ 12 months groups showed: unknown etiology in 9% vs 25%; spasm freedom for 3 months on KD in 18% vs 41%; median time to spasm freedom was 2 vs 6 weeks; relapse after a period of spasm freedom occurred in 66% vs 70%. Conclusions: Although more effective in children ≥ 12 months of age in the first 3 months, spasm freedom in either group was not sustained with KD. KD is recommended as early therapy for refractory ES, but this study suggests clinicians be aware the KD has limited efficacy in long-term control of ES and must be used with other therapies.

Background: West syndrome (WS) is characterized by the onset of epileptic spasms usually within the first year of life. Global developmental delay with/without regression is common. Advances in high-throughput sequencing have supported the genetic heterogeneity of this condition. To better understand the genetic causes of this disorder, we investigated the results of targeted exome sequencing in 29 patients with WS. Methods: Whole exome sequencing (WES) was performed on an Ion ProtonTM and variant reporting was restricted to sequences of 620 known epilepsy genes. Diagnostic yield and treatment impact are described for 29 patients with WS. Results: A definitely/likely diagnosis was made in 10 patients (34%), which included 10 different genes (ALG13, PAFAH1B1, SLC35A2, DYNC1H1, ADSL, DEPDC5, ARX, CDKL5, SCN8A, STXBP1) known to be associated with epilepsy or WS. Most variants were de novo dominant (X-linked/autosomal) except for ARX (X-linked recessive) and ADSL (autosomal recessive). 4 out of 10 (40%) had a genetic diagnosis with potential treatment implications. Conclusions: These results emphasize the genetic heterogeneity of WS. The high diagnostic yield, along with the significant genetic variability, and the potential for treatment impact, supports the early use of this testing in patients with unexplained WS.

Background: Rituximab is a B-cell-depleting monoclonal antibody whose off-label use is funded in Alberta by the Short-Term Exceptional Drug Therapy (STEDT) program. This study describes the use of rituximab for pediatric central nervous system (CNS) inflammatory disorders in Alberta. Methods: Rituximab applications for CNS inflammatory indications in patients < 18 years of age were identified from the STEDT database between January 1, 2012 – December 31, 2019. Patient information was linked to other provincial datasets, including the Discharge Abstract Database, Pharmaceutical Information Network, and provincial laboratory data. Analysis was descriptive. Results: 51 unique rituximab applications were identified, of which 50 were approved. New applications increased from one in 2012 to a high of 12 in 2018. The most common indication was autoimmune encephalitis (other than anti-NMDA receptor encephalitis; n=20, 39%). Most children were approved for a two-dose (n=33, 66%) or four-dose (n=16, 32%) induction regimen. Physician-reported outcomes were available for 24 patients, of whom 14 (58%) were felt to have fully met outcome targets. Conclusions: The use of rituximab for pediatric CNS inflammatory disorders has increased, particularly for the indication of autoimmune encephalitis. This study identified significant heterogeneity in dosing practices and laboratory monitoring, as well as regional disparities in use.

Background: Spinal muscular atrophy (SMA) is the leading genetic cause of infant death and the second most common autosomal recessive disorder; the majority of cases are due to homozygous deletion of SMN1 gene. Methods: This study uses the Canadian Paediatric Surveillance Program to determine the minimum annual incidence of 5q-SMA from birth to 18 years of age in Canada. The complete protocol can be accessed at www.cpsp.cps.ca/surveillance. Results: Eleven cases were reported in 2020. Five (45%) cases were reported from Ontario and the remaining cases were reported from Atlantic Canada and Western Canada. Their median age was 12 months (IQR 6–21); 64% were male. The most common presenting symptoms were delayed motor milestone and hypotonia in 7 (64%) cases. On average, the diagnosis was delayed after the onset of symptoms by three months for SMA Type 1, by eight months for Type 2, and by 18 months for Type 3. Eight (73%) cases received nusinersen as their first disease-modifying treatment. Conclusions: Early recognition and newborn screening are essential to reduce diagnostic delay and enable timely treatment of SMA. Other data sources including the Canadian Neuromuscular Disease Registry and molecular genetic laboratories will be used to estimate the annual incidence of pediatric SMA in Canada.

Background: Duchenne muscular dystrophy (DMD) is a severe progressive neuromuscular disease. This study aimed to estimate the prevalence, healthcare resource utilization (HRU), and medical costs of DMD in Alberta. Methods: This retrospective study linked provincial healthcare administrative data to identify patients with DMD utilizing a modified diagnostic code algorithm, including males <30 years of age. Five-year (April 2012 to March 2017) prevalence estimates were calculated and all-cause direct HRU and costs were examined in the first-year post-diagnosis. Results: Overall, 111 patients (median age: 12.0 years (IQR 4.7-18.3)) with DMD were identified. The estimated five-year period prevalence was 35.72 (95% CI 31.88-39.91) per 100,000 persons. All-cause HRU in the first-year post-diagnosis included a mean (SD) of 0.48 (1.19) hospitalizations (length of stay: 9.37 days (36.47)), 3.96 (6.16) general practitioner visits, 28.52 (62.98) specialist visits, and 20.14 (16.49) ambulatory care visits. Mean (SD) all-cause direct costs were $18,868 ($29,206) CAD in the first-year post-diagnosis. Conclusions: Patients with DMD had multiple interactions with the healthcare system in the year following diagnosis, resulting in substantial direct medical costs. More effective treatment strategies are needed to improve health outcomes and reduce the burden of DMD.

Background: Tumors affecting peripheral nerves in children are rare. Accurate diagnosis ensures that management is appropriate and timely. Methods: We review the clinical presentation and utility of investigations of children with intrinsic tumors affecting peripheral nerves at the Children’s Hospital of Eastern Ontario (CHEO). Results: From 2009-2019, 14 cases were identified. Mean age of symptom onset was 8.2 years (range 0.3 to 17.3 years). Presenting symptoms included painless muscle wasting (2/14), focal muscle weakness (7/14), contracture (1/14), pain (1/14) or a painless, palpable mass (3/14). MRI was useful at differentiating benign pediatric nerve tumors. Peripheral nerve lipomatosis demonstrated a classic “spaghetti string” appearance. Patients with perineurioma showed evidence of enhancing, nodular lesions while intraneural ganglionic cysts display cystic lesion within the nerve. Neurofibromas appear like a “bag of worms” while schwannomas are more eccentrically positioned around the nerve. Nerve conduction studies (NCS) or electromyography (EMG) were performed in 11/14 patients. Biopsies were performed in 9 patients and surgical management in 4 patients. Conclusions: The rare nature of peripheral nerve tumors in children can pose diagnostic challenges. NCS/EMG are important to assist with localization, and MRI important at distinguishing benign tumors. Key MRI, clinical and NCS features can guide management, potentially avoiding invasive procedures.

Background: MR-based vessel wall imaging (VWI) has gained influence in the clinical investigations, and management of pediatric strokes. Limitations still exist in interpreting it as a singular modality. Methods: We present 4 pediatric stroke cases with VWI enhancement. Results: Case 1. 4-year old boy with sickle cell anemia, who developed encephalopathy during a hemolytic crisis. MR-VWI revealed bilateral extracranial internal carotid enhanced narrowing, deemed a secondary vasculopathy, with resolution upon follow-up.

Case 2. 16-year old male presented with left middle cerebral artery (MCA) infarction. VWI revealed left internal carotid terminus and proximal MCA enhancement. Conventional angiography showed abnormalities in mesentric and hepatic arteries. Stability sustained on anticoagulation and immunosuppressive therapy.

Case 3. 10-year old girl, developed bilateral MCA infarctions with enhanced extracranial segments of both ICAs, and narrow PCAs, consistent with Moyamoya vasculopathy. Improved on combined immunosuppressive and anticoagulation therapy.

Case 4. 13-year old boy had an episode of right facial weakness, with a normal neurological exam; with enhancement and narrowing in the left extracranial ICA, likely an intramural hematoma from dissection. He responded to dual anticoagulation therapy. Conclusions: In conclusion, these cases illustrate similarities in vessel wall imaging abnormalities under different clinical contexts, with practical utility in longitudinal follow-up and prognostication.

Background: Neonatal cerebral sinovenous thrombosis (CSVT) can lead to severe brain injury and long-term neurodevelopmental impairments. Previous studies of neonatal CSVT have mainly included term infants. In this study, we examined the clinical and radiological features, treatment and outcome of CSVT in preterm infants. Methods: This was a retrospective cohort study of preterm infants born <37 weeks with radiologically confirmed CSVT. All MRI/MRV and CT/CTV scans were re-reviewed. Clinical and radiological data were analysed using descriptive statistics, ANOVA and chi-square tests. Results: A total of 26 preterm infants with CSVT were included. Of these, 65% were late preterm, 27% very preterm and 8% extreme preterm. Most were symptomatic (seizures 50%, abnormal exam 50%). Radiological features included transverse sinus (85%) and sagittal sinus thrombosis (42%), intraventricular hemorrhage (42%) and venous infarction (19%). Most preterm infants with CSVT (69%) were treated with anticoagulation. Anticoagulation was not associated with new or worsening intracranial hemorrhage. Outcome at follow-up ranged from no impairment (39%), mild impairment (19%), severe impairment (19%) and death (23%). Conclusions: Preterm infants with CSVT are often symptomatic and present with a distinct pattern of brain injury. Anticoagulation treatment of preterm CSVT appeared to be safe. Further studies and treatment guidelines for preterm CSVT are needed.

Background: Approximately 1,000 children present with AIS annually in North America. Most suffer from long-term disability. Childhood AIS is diagnosed after a median of 23 hours post-symptom onset, limiting thrombolytic treatment options that may improve outcomes. Pediatric stroke protocols decrease time to diagnosis. AIS treatment is not uniform across Canada, nor are pediatric stroke protocols standardized. Methods: We contacted neurologists at all 16 Canadian pediatric hospitals regarding their AIS management. Results: Response rate was 100%. Seven centers have an AIS protocol and two have a protocol under development. Seven centers do not have a protocol – two redirect patients to adult neurology, and five use a case-by-case approach for management. Analysis of the seven AIS protocols reveals differences: 1) IV-tPA dosage: age-dependent 0.75-0.9 mg/kg (n=1) versus age-independent 0.9 mg/kg (n=6), with maximum doses 75 mg (n=1) or 90 mg (n=6); 2) IV-tPA lower age cut-off: 2 years (n=4) versus 3, 4 or 10 years (n=1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (n=3), <5 (n=1), or <6 (n=3); 4) Pre-treatment neuroimaging: CT (n=3) versus MRI (n=4); 5) Intra-arterial tPA use (n=3). Conclusions: The seven Canadian pediatric AIS protocols show prominent differences. We plan a teleconference discussing a Canadian pediatric AIS consensus approach.

Background: Curriculum maps outline the content of an educational program identifying links between targeted outcomes, educational opportunities, and assessments. The transition to Competence by Design (CBD) in Canadian specialty residency programs requires thoughtful reorganization of educational programming. A curriculum map may assist with understanding the existing curriculum and thereby facilitate planning for CBD. Methods: A map of the pediatric neurology residency curriculum at the University of Calgary was constructed by linking objectives with related learning activities and assessments. Qualitative line-by-line analysis was then conducted to identify gaps in the existing curriculum. The map was used as a framework to plot CBD outcomes and curricular structure as these were established. Results: Generating the traditional curriculum map was time-consuming, requiring 48 hours. Careful review identified several objectives that did not link to formal learning activities or assessments. Many such gaps were recognized to link to non-clinical activities. Using the scaffold of the traditional curriculum reduced the time required for mapping the planned CBD curriculum to 4 hours. Conclusions: The creation of a curriculum map prior to transition to CBD improved understanding of the existing curriculum and will facilitate transition to CBD. Ongoing evaluation of the fit of our predicted CBD map will support effective implementation.

Background: Improved understanding of factors predictive of emergency department (ED) visits in children with cerebral palsy (CP) can help optimize healthcare use. We sought to identify the pattern of ED consultations in these children. Methods: Data from the Registre de paralysie cérébrale du Québec and provincial administrative databases were linked. The CP cohort was comprised of children born between 1999 and 2002. Data pertaining to ED presentations between 1999 and 2012 were obtained. Relative risks were calculated to identify factors associated with increased ED visits. Peers without CP were selected from administrative databases and matched in a 20:1 ratio. Chi-square tests and Student’s T-tests were used to compare the two cohorts. Results: 301 children with CP and 6040 peer controls were selected. Ninety-two percent (92%) of the CP cohort had at least one ED visit, compared to 74% amongst controls. Children with CP had an increased risk of high ED use compared to peers (RR 1.40 95% CI 1.30-1.52). Factors predictive of high ED use were comorbid epilepsy, severe motor impairment and low socioeconomic status. Conclusions: Children with CP have a higher need for urgent health assessments than their peers, resulting in increased use of ED services. System factors and barriers should be investigated.

Background: Children with pathogenic variations in SCN8A can present with early infantile epileptic encephalopathy-13, benign familial infantile seizures-5 or intellectual disability alone without epilepsy. In this case series, we discuss six children with variants in SCN8A managed at BC Children’s Hospital. Methods: We describe clinical and genetic results on six individuals with SCN8A variants identified via clinical or research next-generation sequencing. Functional consequences of two SCN8A variants were assessed using electrophysiological analyses in transfected cells. Results: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort are described in the table below. Functional analysis supported gain-of-function in P2 and loss-of-function in P4. Conclusions: Our cohort expands the clinical and genotypic spectrum of SCN8A-related disorders. We establish functional evidence for two missense variants in SCN8A, including LoF variant in a patient with intellectual disability, and autism spectrum disorder without seizures.

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Background: Children and Adolescents with rare neurogenetic disorders often have no known cure or disease modifying treatments. Recent advancements in treatments are offering much needed hope to these patients and families. However, these treatments are extremely costly, have complex administration requirements and have many unknown long-term risks and outcomes. Methods: In this presentation, we will discuss our experiences with the implementation process, including developing intricate care pathways, collaborating with multiple disciplines and services, supporting and advocating for our patients and families, and interacting with government agencies and pharmaceutical companies. Case studies will highlight the positive impact these treatments are making on the lives of children and adolescents with rare neurological disorders. Results: Spinal muscular atrophy and Neuronal Ceroid Lipofuscinosis Type 2 are both rare and devastating neurodegenerative conditions with significant morbidity and mortality. Health Canada and government funding agencies recently approved Nusinersen, Onasemnogene abeparvovec for the treatment of SMA and Cerliponase alfa for the treatment of CLN2, leading us to swiftly integrate these treatments into our standard of care. Conclusions: While implementing these novel therapies into clinical practice can be both challenging and rewarding, neuroscience nurses are positioned at the forefront to be leaders in this process at both organizational, national, and international levels.

Background: We describe an infant with a diagnosis of GM3 synthase deficiency, presenting with severe neuroirritability from birth. He required multiple admissions due to extreme agitation and caregiver burnout. Multiple pharmacological agents were tried, and the effect of each medication was modest and short-lasting at best. The literature on the management of neuroirritability in children with progressive genetic and metabolic conditions is sparse, and a neuroirritability management protocol has yet to be developed at our institution. Methods: We searched for relevant primary research and articles on PubMed. We reviewed the evidence of each pharmacological agent and added non-pharmacological strategies. We developed management guidelines for neuroirritability at our hospital. This protocol was reviewed by several pediatric neurologists and pediatric palliative care specialists at the Stollery and SickKids Hospitals. Results: We present the Pediatric Neuroirritability Management Protocol for the Stollery Children’s Hospital. Conclusions: Further study is required to assess whether this protocol can be adapted to treat irritability in the context of other neurological conditions such as hypoxic-ischemic encephalopathy and non-accidental injury. In addition, we will expand our guidelines to include other symptoms such as spasticity, dystonia, and autonomic dysfunction.

Background: Patients with DNM1-encephalopathy almost exclusively have missense variants, mostly in the GTPase domain of DNM1. Delayed myelination has been reported in at least three patients with DNM1-encephalopathy, all with missense mutations in the DNM1 central domain. Only one DNM1 splice-site variant has previously been reported, and the authors questioned whether the variant accounted for all aspects of the patient’s phenotype. Methods: Case-Report. Results: Our patient had hypotonia and brief multifocal tonic seizures from age-1-month. He still has profound global developmental delay, daily seizures and microcephaly. MRI-Brain at age-21-months showed T2 hyperintensity in the bilateral periventricular and subcortical white matter; spectroscopy showed a questionable lactate peak and an elevated choline peak relative to N-acetylaspartate. Clinical gene-panel identified a heterozygous de novo pathogenic variant in intron 9 of DNM1 (c.1197-8G > A; IVS9- 8G>A). In-silico tools categorized this variant as deleterious secondary to a splicing defect. RT-PCR analysis on peripheral blood was unsuccessful as DNM1 expression is extremely low outside of the brain. Conclusions: Our patient carried the same DNM1 variant previously reported, indicating this is a recurrent pathogenic splice-site variant. The spectroscopic abnormalities suggest a possible element of demyelination in DNM1 variants of the central domain, though the mechanism remains unclear.

Background: Attention and executive function (EF) deficits in children negatively impact academics, social interactions, and overall quality of life. Children with other brain-based disorders are at high risk for attention and EF concerns, but the effects of these impairments are not well studied in the literature. The Complex Attention and Executive Function Clinic at the Alberta Children’s Hospital collected baseline data on patients referred for concerns of attention deficits co-occurring with diagnosed neurologic illness/injury, or neurodevelopmental disorder (NDD). Methods: The Behaviour Rating Inventory of Executive Function (BRIEF-2), Behaviour Assessment System for Children (BASC-3), Parenting Stress Index (PSI-4) and medical and past treatment information were collected on initial clinic visit for patients aged 5-15 years. Results: BRIEF-2 Global Executive Composite demonstrated 88.9% of children had clinically elevated scores. Clinically significant scores were observed in 55.5% for BASC-3 Adaptive Skills index and 40% of parents in PSI-4 Total Stress scores. Conclusions: Children with neurologic illness/NDDs are at high risk of clinical impairments in attention and EF. In children referred for attention and behavioural regulation, there is clinically significant increased reporting of executive function impairment out of proportion to other behavioural difficulties. The clinic aims to improve overall functioning through treatment of unmanaged attention and EF deficits.

Background: Interictal epileptiform discharges (IEDs) are known as epilepsy biomarkers for seizure detection, and It is essential for clinicians to detect them from from physiological events with similar temporal frequency characteristics. Methods: We analyzed the SEEG recordings obtained from patients with medically-resistant epilepsy (MRE) implanted with DE at the Western University Hospital Epilepsy Unit. The data were cleaned, denoised, montaged and segmented based on the clinical annotations, such as sleep intervals and observed Ictals. For event detection, the signal waveform and its power were extracted symmetrically in non-overlapping intervals of 500 ms. Each waveform’s power across all detected spikes was computed and clustered based on their energy distributions. Results: The recordings included thirteen sessions of 24 hours of extracellular recordings from two patients, with 312 hours extracted from four hippocampus electrodes anterior and posterior hippocampus. Our results indicate IEDs carrying the most different characteristics in the bands [25-75] Hz; SWR, on the other hand, are distributed between [80-170] Hz. Conclusions: Our algorithm detected and successfully distinguished IED from SWRs based on their carrying energy during non-sleep periods. Also, the most powerful spectral features that they were distinguished from occur in [15-30] Hz and [75-90] Hz.

Background: For over 40 years, the objective structured clinical examination (OSCE) has been a part of medical education, eventually finding its way into most aspects of clinical training and evaluation. However, the EEG/epilepsy fellowship training has not classically involved OSCE evaluations. Methods: We designed and implemented a formative OSCE for pediatric and adult EEG/epilepsy fellows in Montreal, Quebec, Canada. The examination was offered in French and English. Stations included: technical issues, short cases, a long case, and communication. We solicited post-examination feedback from all participants via anonymous electronic survey after they had completed the Canadian Society for Clinical Neurophysiology (CSCN) EEG examination. We asked questions surrounding utility of the examination, areas for improvement, and whether the participant had been successful in passing the CSCN examination. Results: Six fellows took the initial formative OSCE. All six reported passing the subsequent CSCN examination. All participants reported the OSCE as useful in examination preparation. The communication station was consistently ranked as the least useful station, an unsurprising finding given that the CSCN examination does not involve a communication component. Conclusions: OSCE is an effective tool in assessment of the level of competence of EEG/epilepsy fellows, and as preparation for the CSCN EEG examination.

Background: Assessment of patients for temporal lobe epilepsy (TLE) surgery requires multimodality input, including EEG to ensure optimal surgical planning. Often EEG demonstrates abnormal foci not detected on clinical MRI. 7T MRI provides improved resolution and we investigated its utility to detect potential abnormalities associated with EEG. Methods: Images were acquired on 7T MRI scanner (N=13) in oatients with TLE. Evaluation of 7T imaging for focal abnormalities was performed. Correlation of 7T MRI findings with EEG of focal slowing or interictal epileptic spikes (IEDs) and seizures was performed. Results: Assessment of 7T MRI demonstrated concordance with TLE in 8/13 cases. Three cases exhibited abnormal 7T MRI abnormalities not detected by 1.5 T MRI. Eleven out of 13 cases had EEG findings without anatomic correlates on MRI, with IEDs localizing to contralateral temporal, frontal, and parieto-occipital lobes. 7T images did not reveal focal anatomical abnormalities to account for the EEG findings in these patients. Conclusions: To our knowledge, this is the first study to investigate the role of 7T MRI in relation to EEG abnormalities. 7T RI findings show concordance with clinical data. 7T MRI did not reveal anatomical findings to account for EEG abnormalities, suggesting that such changes may be functional rather than anatomical.

Background: Rapid eye movement sleep (REM) is divided into phasic and tonic microstates. Phasic REM is defined by presence of REMs with reportedly greater antiepileptic effect. We assessed whether quantitative EEG (QEEG) software can detect REM microstates. Methods: We applied artifact reduction and detection trends from QEEG software (Persyst 14) on 18 patients undergoing 30 day-night high density EEG recordings in the epilepsy monitoring unit. We identified phasic REM as 10-second epochs of previously human-scored REM that demonstrated presence of either vertical or horizontal eye movements on the QEEG artifact detection panel. Remaining epochs were identified as tonic REM. Results: Out of 91.2 average minutes of REM (range 24.5-167.5) per recording, a mean of 2.5% (range 0-18.9%) demonstrated eye movements intensive enough for QEEG artifact detection to be identified as phasic REM. On average, only 40% (range 0-500%) of eye movements per recording was flagged as vertical. Conclusions: These findings provide proof-of-concept that QEEG can automatically assess REM microstructure by readily detecting phasic and tonic REM. These findings also confirm that most REMs are horizontal. Having the ability to easily and automatically detect phasic versus tonic REM can help further future studies examining the antiepileptic effect of REM sleep.