Background: Generalized myasthenia gravis (gMG) is a potentially life threatening chronic autoimmune disease that can impair patients’ ability to work effectively and increase reliance on public support benefits. A public economic framework was used to explore how treatment influences patients’ and caregivers’ economic activity, including tax revenues and public support in Canada. Methods: Natural history of gMG was simulated using a multi-state Markov cohort model. Health states were based on MG Activities of Daily Living (MG-ADL) total score in patients with AChR-Ab+ refractory gMG. Treatment, costs, and economic outcomes of patients taking efgartigimod were compared with alternative therapeutic options. Canadian public support benefits were based on official government sources. Results: Improved MG-ADL states predict higher workforce participation, lower rates of disability and less caregiving needs, resulting in higher tax revenues and less public support costs. Compared to alternative therapeutic options, efgartigimod is estimated to yield lifetime fiscal gains of $458,755 that exceed the incremental cost of $291,073, suggesting the Canadian government receives $1.6 for every $1.0 spent on efgartigimod for the treatment of gMG. Conclusions: Compared with alternative options, efgartigimod generated a positive fiscal return for the Canadian governments with additional savings from disease management, public benefits, and averted tax revenue losses.

In recent years there have been major socio-economic changes within Afghanistan such that the present public health burden of soil-transmitted helminths (STH), especially that within school-aged children, remains to be determined. A baseline parasitological survey was therefore carried out in four defined areas of Afghanistan to better assess the distribution, prevalence and intensity of STH infections prior to a nationwide de-worming campaign beginning within World Food Programme assisted schools. A cross-sectional examination of 1001 children aged between 8 and 15 years old revealed that approximately half (47.2%) were infected with at least one STH. Infections with Ascaris lumbricoides were most widespread (40.9%) and elevated prevalences were detected in urban environments; for example, schoolchildren in Kabul were more likely to be infected (OR=2.2, 95% CI 1.6–3.0) than elsewhere and these infections were often of higher intensity (OR=7.6, 95% CI 4.9–11.8). Trichuris trichiura (9.9%) and hookworms (0.7%), previously unknown from Afghanistan, were encountered. The blood haemoglobin concentration of surveyed children was also assessed: 4% resulted to be anaemic (Hb<11 g dl−1), and 0.4% to be severely anaemic (Hb<7 g dl−1).

Background: Seizures in childhood absence epilepsy (CAE) are typically 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 treatment resistance in a cohort of CAE at a single centre. Methods: We retrospectively reviewed patients with CAE diagnosed between January 1999 and December 2016 with at least 1-year follow-up. Treatment resistance was defined as failure to respond to two appropriate ASMs. Exclusion criteria included eyelid myoclonia with absence, myoclonic absence, and generalized tonic-clonic (GTC) seizures prior to absence seizures. Results: The study population comprised 164 patients (65 males) with mean age at seizures onset of 6.1years. 21% had treatment-resistant seizures. The first ASM was Ethosuximide (63.4%), Valproic acid (23.2%), and Lamotrigine (6.7%). 32.9% of children had learning disabilities, 28.7% ADHD, and 12.8 % anxiety.

A stepwise binary logistic regression analysis identified GTC seizures, learning disability (LD) and ongoing general spike and wave on EEG as predictors of treatment resistance. At last follow-up (average of 5.4 years), 43.3% of children were seizure-free off ASMs. Conclusions: 21% of children with CAE had treatment-resistant seizures. LD, GTC and failure of normalization of the EEG were associated with treatment resistance.

Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ [145 − 350] MHz.

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: 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: 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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Initiatives to optimise preconception health are emerging following growing recognition that this may improve the health and well-being of women and men of reproductive age and optimise health in their children. To inform and evaluate such initiatives, guidance is required on indicators that describe and monitor population-level preconception health. We searched relevant databases and websites (March 2021) to identify national and international preconception guidelines, recommendations and policy reports. These were reviewed to identify preconception indicators. Indicators were aligned with a measure describing the prevalence of the indicator as recorded in national population-based data sources in England. From 22 documents reviewed, we identified 66 indicators across 12 domains. Domains included wider (social/economic) determinants of health; health care; reproductive health and family planning; health behaviours; environmental exposures; cervical screening; immunisation and infections; mental health, physical health; medication and genetic risk. Sixty-five of the 66 indicators were reported in at least one national routine health data set, survey or cohort study. A measure of preconception health assessment and care was not identified in any current national data source. Perspectives from three (healthcare) professionals described how indicator assessment and monitoring may influence patient care and inform awareness campaign development. This review forms the foundation for developing a national surveillance system for preconception health in England. The identified indicators can be assessed using national data sources to determine the population’s preconception needs, improve patient care, inform and evaluate new campaigns and interventions and enhance accountability from responsible agencies to improve preconception health.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Background: SMA1 is a neurodegenerative disease caused by bi-allelic survival motor neuron 1 gene (SMN1) deletion/mutation. In the phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA1 patients. We report preliminary data of STR1VE, a pivotal study (NCT03306277) evaluating efficacy and safety of a one-time intravenous AVXS-101 infusion. Methods: STR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged <6 months (bi-allelic SMN1 loss, 2xSMN2). Primary outcomes: independent sitting for ≥30 seconds (18 months) and survival (14 months). Secondary outcomes: ability to thrive and ventilatory support (18 months). Exploratory outcomes: CHOP-INTEND and Bayley Scales of Infant and Toddler Development scores. Results: Enrollment is complete with 22 patients dosed. Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support, and all exclusively fed by mouth. Mean baseline CHOP-INTEND score was 32.6 (17.0–52.0), which increased 6.9 (-4.0–16.0, n=20), 10.4 (2.0–18.0, n=12), and 11.6 (-3.0–23.0, n=9) points at 1, 2, and 3 months; updates provided at congress. Conclusions: Preliminary data from STR1VE show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.

Background: Status epilepticus (SE) is the most common pediatric neurological emergency. Timely treatment is crucial, yet administration of rescue medications is often delayed and under-dosed. We aim to improve SE management by ensuring that every child at risk of SE in our province has an individualized seizure action plan (SAP) outlining the steps that should be taken during SE. Methods: A survey was distributed to parents of epilepsy patients aged 1 month to 19 years. Primary outcome was percentage of patients with SAPs. Secondary outcome was parental interest in a SAP mobile application. Following chart review, univariate and multivariate analysis was performed to identify variables that predict whether patients have SAPs. Results: Of 192 participants, 61.5% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of having a SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82.2% of patients with SAPs. 83.3% of parents were interested in a SAP mobile application. Conclusions: This is one of the first studies to examine SAP prevalence in a pediatric epilepsy population. There is a need to increase the percentage of epilepsy patients with SAPs. Most parents would find a SAP mobile application valuable in their child’s management.

Cougar Mountain Cave is located in Oregon's Fort Rock Basin. In 1958, avocationalist John Cowles excavated most of the cave's deposits and recovered abundant fiber, lithic, wood, and osseous artifacts. A crew from the University of California, Davis returned to the site in 1966 to evaluate the potential for further research, collecting additional lithic and fiber artifacts from disturbed deposits and in situ charcoal from apparently undisturbed deposits. Because Cowles took few notes or photographs, the Cougar Mountain Cave collection—most of which is housed at the Favell Museum in Klamath Falls, Oregon—has largely gone unstudied even though it contains diagnostic artifacts spanning the Holocene and, potentially, the terminal Pleistocene. We recently submitted charcoal and basketry from the site for radiocarbon dating, providing the first reliable sense of when Cougar Mountain Cave was first occupied. Our results indicate at least a Younger Dryas age for initial occupation. The directly dated basketry has provided new information about the age ranges and spatial distributions of diagnostic textile types in the northwestern Great Basin.