Background: Pediatric occipital epileptiform discharges (OEDS) occur in various clinical settings, including benign and symptomatic epilepsies. The study objective is to determine electro-clinical predictors for aetiology and prognosis in children with OEDs. Methods: 205 patients with OEDs were classified into seizure groups: symptomatic (n=98), idiopathic focal (IF) (n=57), idiopathic generalized (IG) (n=18), no-seizures (n=27) and febrile seizures (n=5). Results: The median age of seizure onset was 3 years (range: 0-19). There was more EEG background slowing (P<0.05) in the symptomatic; photosensitivity (P<0.0001) and GSW (P<0.0001) in IG; and presence of consistent EEG spike dipole in IF group. The symptomatic had more DD (P< 0.0001), autism (P <0.019), and school difficulties (P<0.001) than the IF and IG groups, but not different from the no-seizure group. Conclusions: OEDs with consistent dipole spike is predictive of IF epilepsy. In contrast to frontal and temporal lobe epilepsy, only 30% with symptomatic epilepsy had occipital-predominant neuro-imaging abnormalities. Notably, neuro-psychiatric co-morbidities were similar between the symptomatic and no-seizure group.

Background: Newborns with hypoxic-ischemic encephalopathy (HIE) are at high risk for seizures, the majority of which have no clinical signs and therefore require continuous electroencephalographic (cEEG) monitoring for their detection. We sought to determine which neonates are at highest risk for seizures in order to optimize allocation of scarce cEEG resources. Methods: We identified term neonates diagnosed with HIE who underwent at least 24 hours of protocol-based cEEG monitoring between 2016 and 2019. We quantified seizure incidence, timing and burden, and correlated these with potential risk factors such as HIE severity, use of therapeutic hypothermia, preceding suspected clinical seizures, amplitude-integrated EEG (aEEG) background and patterns suspicious for seizures, and use of anti-seizure drugs. Results: cEEG monitoring was completed in 218 neonates with HIE, of whom 164 (75%) underwent therapeutic hypothermia. Preceding clinical/aEEG seizures occurred in 147 (67%), 99 (67%) of whom had been cooled but only 22 (10%) had cEEG-confirmed seizures. Characterization of seizure burden and correlation with potential risk factors is ongoing. Conclusions: Although seizures are commonly suspected in neonates with HIE, they are infrequently confirmed during cEEG monitoring, creating opportunities for more efficient risk-based allocation of cEEG resources.

Background: Hormonal therapy is a standard treatment for infantile spasms. The high doses given and long treatment duration expose patients to the risk of adrenal insufficiency (AI). This study aims to quantify the incidence of AI among children with infantile spasms treated with corticosteroids and/or adrenocorticotropic hormone (ACTH). Methods: A retrospective chart review of patients treated for infantile spasms was performed between January 2009 to March 2020 in one pediatric specialized hospital. Variables collected included patient and treatment characteristics, risk factors of AI and adrenal function testing. Analysis included descriptive statistics. Results: Thirty-one patients met the inclusion criteria and received a total of 33 separated courses of treatment. Adrenal function following each course of treatment was evaluated in all patients. AI occurred in 25/33 (76% [95CI 58-89]) children. There was no predictive factor of AI. No drug regimen was deemed safe. The two patients (6%) with an acute adrenal crisis were the youngest of the cohort. Conclusions: Adrenal suppression is frequent and can lead to adrenal crisis after standard hormonal therapy for infantile spasms. A routine laboratory assessment of adrenal function should be done for all patients. Hydrocortisone replacement therapy should be given until testing results are obtained, particularly for younger infants.

Background: Infantile spasms (IS) is an epileptic encephalopathy, characterized by epileptic spasms, hypsarrhythmia, and developmental regression. This is a retrospective case series detailing the experience in children with IS who have undergone epilepsy surgery at The Hospital for Sick Children (HSC). Methods: Records of 223 patients from HSC were reviewed. Patients were included if they had a current or previous history of IS with a lesion detected on MRI/PET scan who underwent epilepsy surgery. Results: Nineteen patients were included. The etiology of IS was encephalomalacia in six patients (32%), malformations of cortical development in 11 patients (58%), atypical hypoglycaemic injury in one patient (0.5%), and partial hemimegalencephaly in one patient (0.5%). The median age at the onset of IS was five months. The median age at surgery was 18 months. Nine patients (47%) underwent hemispherectomy and 10 patients (53%) underwent lobectomy/lesionectomy. Fifteen patients (79%) were considered ILAE Seizure Outcome Class 1. Developmental outcome was improved in 14/19 (74%) and stable in 5/19 (26%) patients. Conclusions: Even with a generalized EEG pattern such as hypsarrhythmia, patients should be considered for focal resective surgery. Early surgical intervention shortens the duration of active epilepsy thus limiting the potentially irreversible effects of on-going seizures.

Background: We aimed to study the proportion of patients with DRE and pre-existing VNS device, who show improvement of at least one class in McHugh seizure outcome classification at last follow up after generator replacement with cardiac based VNS device. Methods: We retrospectively reviewed children with DRE with the older VNS model (102) who underwent battery replacement with the AspireSR®, model 106 since September 2016 at our institution. We assessed the seizure outcomes since the first VNS device insertion till the last follow up after AspireSR® (with cardiac-based seizure detection) using McHugh seizure outcome classification. Results: The study population was comprised of 15 patients. The mean age at seizure onset was 2.7 years old, with mean age of initial VNS1 placement being 10.1 years and mean age of replacement with VNS2 being 14.9 years of age. Three of the fifteen patients had reported status epilepticus prior to initial VNS insertion, and none reported episodes following insertion. Two patients showed at least one class improvement in McHugh seizure outcomes at last follow up after VNS2. Conclusions: Through our preliminary data at the present time, we note that the majority of our patients maintains their seizure control following replacement with VNS2 with a few showing improvement.

Background: Epilepsy, a common neurologic condition, instigates a large number of emergency room (ER) visits annually. This project aims to retrospectively review the patterns and characteristics of Alberta ER visits by pediatric epilepsy patients. Methods: Methods: Alberta Health administrative databases, including the Inpatient Discharge Abstract Database, the National Ambulatory Care Reporting System, Diagnostic Imaging and Medical Laboratory, were used to identify ER utilization patterns among children with epilepsy in Alberta, Canada between 2012–2018. Results: Results: Of 5,419 pediatric epilepsy ER patients between 2012–2018 in Alberta, 59% were developmentally delayed children. Children in this particular group, when compared to developmentally normal children with epilepsy, had the following characteristics: they were significantly more likely to utilize ERs in children’s hospitals versus other hospitals; they presented at a significantly younger age; they had a significantly longer length of stay; they had higher triage scores; they were subjected to significantly more investigations; and they had significantly more hospital admissions for epilepsy. Conclusions: Discussion: This novel Alberta-wide study of resource utilization of pediatric epilepsy patients shows that developmentally delayed children with epilepsy use significantly higher resources compared to developmentally normal children with epilepsy. Whether this is justified or not requires further study.

Background: To assess the response to high dose daily nocturnal diazepam (HDD) in children with encephalopathy associated with electrical status epilepticus in sleep (ESES). Methods: A prospective cohort of patients (4-12 years), newly diagnosed with ESES, initiated on the first course HDD, was followed for ≤ 1-year. Sleep EEG scores (SES) pre and post HDD were evaluated. An EEG grading system based on both sleep spike wave index (sSWI) (Grade: 1-4) and distribution of epileptiform discharges (Grade: 0-4) was used and summed to yield an aggregate SES (ASES) (Grade: 1-8). Results: Eighteen eligible children (M:F 12:6; median age, 7.6 years) were initiated on first course HDD (median, 0.5 mg/kg/d). sSWI decreased from 85.7% (mean, SD 13.9) to 32.6% (mean, SD 37.1) at subsequent EEG (95% CI = -70.60- -35.62; p < 0.001). ASES decreased from 6.5 (SD 1.3) to 3.1 (SD 1.9) (95% CI = -4.17- -2.60; p < 0.001). EEG relapse after a period of improvement occurred in 10 children. Minimal response to HDD occurred in 2 children. Five patients manifested mild side effects; behavior (2), hyperactivity (2), and lethargy (1). Conclusions: HDD safely and significantly reduces both SWI and aggregate sleep EEG score in children with ESES.

Background: Seizures in childhood absence epilepsy (CAE) are usually easily controlled with anti-seizure medications (ASMs). Factors predictive of treatment resistance remain unclear. Our objectives were to assess prevalence of neuropsychiatric problems and factors influencing refractoriness in a cohort of CAE at a single centre. Methods: We retrospectively reviewed patients with CAE (ILAE 2017 classification) diagnosed between January 1999 and December 2016 with at least 1-year follow-up. Treatment resistance was defined as failure to respond to two or more appropriate ASMs. Exclusion criteria included eyelid myoclonia with absence, myoclonic absence, and generalized tonic-clonic (GTC) seizure before developing absences. Results: The study population comprised 164 patients (65 males) 6.25-year-old on average at absence onset. 22% had treatment-resistant seizures. The first ASM was Ethosuximide in 63.4%, Valproic acid in 23.2%, and Lamotrigine in 6.7%. Statistical differences between response groups included developing a second seizure type specifically GTC, the second and third ASM, and absence of EEG normalization. At last follow-up, 43.3% of children were seizure-free off ASMs. 32.9% of children had learning disabilities, 28% ADHD, and 12.8 % anxiety. Conclusions: 22% of children with CAE had treatment-resistant seizures. Photoparoxysmal response was not predictive of treatment resistance. Neuropsychiatric problems were common with learning disabilities increased with refractory absences.

Background: Epileptic discharges localized to the midline vertex are rare. However, they have been associated with intractable seizures and severe long-term consequences in the developing brain. Our study aimed to understand the etiology of pediatric midline seizures and define post-surgical seizure outcomes. Methods: We reviewed charts, electroencephalography (EEG), and neuroimaging studies of ten pediatric patients with epileptic discharges localized to the midline vertex in the Comprehensive Epilepsy Program. The seizures were classified according to the International League Against Epilepsy criteria, patient age, sex, neuroimaging results, seizure etiology and outcomes were obtained. Results: Age of seizure onset was within the first 10 years of life in 90% of patients, with focal seizures being the most prevalent. Focal cortical dysplasia (FCD) was the most common etiology present in 50% of patients. These children had normal neuroimaging studies and intractable epilepsy. However, seizure freedom was achieved following surgical resection of the epileptogenic zone. Conclusions: We demonstrated that patients with midline epileptic discharges are associated with intractable focal seizures and early seizure onset. Despite normal neuroimaging reports, FCD was the most common pathology. Thus our study suggests early localization and resection of the epileptogenic zone may be beneficial for achieving seizure freedom in children with this electroclinical syndrome.

Background: Lennox-Gastaut syndrome (LGS) is a severe form of pediatric epilepsy that is classically defined by a triad of drug-resistant seizures, characteristic EEG patterns, and intellectual disability. Long-term prognosis is generally poor with progressive intellectual deterioration and persistent seizures. At present, there are few reported cases of LGS and Trisomy 21 (T21) in the literature. To further delineate the spectrum of epilepsy in T21, we reviewed children with T21 and LGS at one center over 28 years. Methods: This is a retrospective case series. At our institution, all EEG results are entered into a database, which was queried for patients with T21 from 1992-2019. Pertinent electro-clinical data was obtained from medical records. Results: 63 patients with T21 and epilepsy, 6 (10%) had LGS and were included in the study. Four of the six patients were male and 5/6, had neuro-imaging, which was normal. Follow-up ranged from 3-20 years. Notably, 5/6 had predominant myoclonic seizures throughout the course of their epilepsy, associated with generalized spike-wave discharges. Conclusions: Myoclonic seizures appear to be a predominant seizure type in patients with T21, suggestive that T21 patients may have a unique pattern of LGS.

Background: Data on intravenous lacosamide use in young pediatric patients is scarce, especially of pre-school age. Methods: We retrospectively reviewed the medical records of all patients less than 6 years old who received intravenous lacosamide at our tertiary pediatric hospital. Data on dose, timing and order of administration was collected. Clinical and electrographic response was independently assessed with EEG interpretation blinded to time of administration. For adverse effects surveillance, heart rate was noted before and 1 hour after dose. Results: Eleven patients (8 boys), received lacosamide between 2013 and 2018. Mean age was 2 years (11 days – 5,3 years). Medical indications were: refractory status epilepticus (n=6), repetitive seizures (n=4), and inability to take oral lacosamide (n=1). On average, lacosamide was the fifth (1st-8th) IV antiepileptic drug administered 78 hours (SD 11 hours) after presentation. The most frequent dose was 5 mg/kg. Clinical response was confirmed in 7 patients, while electrographic response was proven in 3 patients. Seizure relapse at 24 hours was noted in 6 patients. No bradycardia occurred post-lacosamide. Conclusions: Although very safe, therapeutic response to lacosamide in young pediatric patients was inconclusive, mostly due to delay in administration, suboptimal dose, and high number of other IV antiepileptic drugs previously given.

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.