Background: To clarify the landscape of molecular diagnoses (MDs) in early-onset epilepsy individuals, we determined the prevalent MDs stratified by age at seizure onset (SO) and the time to MD in children with SO <36 months of life. Methods: A panel of up to 302 genes associated with epilepsy was utilized and ordering physicians provided the age of SO. Diagnostic yield analyses were performed for SO ages including <1 mo, 1-2 mo, 3-5 mo, 6-11 mo, 12-23 mo, and 24-35 mo. The time to MD (MD age - SO age) was determined for the top 10 genes in each SO category. Results: 15,074 individuals with SO <36 months of life were tested. Predominant MD findings are as follows: KCNQ2 in neonates with SO at <1mo, KCNQ2 and CDKL5 for SO between 1-2 mo, PRRT2 and SCN1A for SO between 3-11 mo, and SCN1A for SO between 12-36 months. The median time to MD varied by gene. For example, there was no delay in the median time to MD for the GLDC, KCNQ2, and SCN2A genes while the median delay for MECP2, SLC2A1, and other genes was ≥ 12 months. Conclusions: These data highlight the importance of comprehensive early testing in children with early-onset epilepsy.

Brain magnetic resonance imaging (MRI) studies of clinical populations often require comparison to a normative ‘control’ cohort, usually of similar age/sex, scanned with the same protocol. The goal here was to create a normative brain MRI database of common quantitative methods to be used in comparisons with a variety of neurological disorders across the lifespan. 378 neurotypical controls (aged 5–90 years; median 31 years; 216 females, 162 males) completed brain MRI, cognitive testing, clinical assessment, and a demographics questionnaire. In addition, this large normative sample will yield novel insight into healthy brain development and aging.

Background: SMA affects individuals with a broad age range and spectrum of disease severity. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral SMN2 pre-mRNA splicing modifier. Methods: SUNFISH is a multicenter, two-part, randomized, placebo-controlled, double-blind study in patients with Types 2/3 SMA. Part 1 assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in patients with Types 2/3 SMA. Part 2 assessed the efficacy and safety of the selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. In Part 2, participants were treated with risdiplam or placebo for 12 months, then received risdiplam in a blinded manner until month 24. At month 24, patients were offered the opportunity to enter the open-label extension phase. Results: Change from baseline in MFM32 total score (Part 2- primary endpoint) in patients treated with risdiplam versus placebo was met at month 12. These increases in motor function were sustained in the second and third year after risdiplam treatment. Here we present 4-year efficacy and safety data from SUNFISH. Conclusions: SUNFISH is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of individuals with SMA.

Low confidence with the neurological examination may contribute to primary care physicians’ discomfort with neurology and a low threshold to refer patients. We surveyed primary care physicians in Quebec about their last three referrals to neurology to evaluate what role the neurological examination played in their decision. Twenty-six physicians answered concerning 73 patient referrals. We found that primary care physicians use the neurological examination to reinforce their decision but rarely depend on the findings. Our results suggest that improving history-taking rather than examination skills may have more impact on neurology referrals, influencing quality of referral information above quantity of referrals.

We investigated the effects of transcranial alternating stimulation (tACS) in patients with insomnia. Nine patients with chronic insomnia underwent two in-laboratory polysomnography, 2 weeks apart, and were randomized to receive tACS either during the first or second study. The stimulation was applied simultaneously and bilaterally at F3/M1 and F4/M2 electrodes (0.75 mA, 0.75 Hz, 5-minute). Sleep onset latency and wake after sleep onset dropped on the stimulation night but they did not reach statistical significance; however, there were significant improvements in spontaneous and total arousals, sleep quality, quality of life, recall memory, sleep duration, sleep efficiency, and daytime sleepiness.

We previously showed that a fully automated voice recognition analog of the Symbol Digit Modalities Test (VR-SDMT) is sensitive in detecting processing speed deficits in people with multiple sclerosis (pwMS). We subsequently developed a French language version and administered it to 49 French-Canadian pwMS and 29 matched healthy control (HC) subjects. Significant correlations between the VR-SDMT and traditional oral SDMT were found in the MS (r = −0.716, p < 0.001) and HC (r = −0.623, p < 0.001) groups. These findings in French replicate our previous findings and confirm the utility of voice recognition software in assessing cognition in pwMS.

Background: Perinatal arterial ischemic stroke (PAIS) is a focal brain injury in term neonates, identified postnatally but presumed to occur around birth. Early risk detection and targeted treatments are limited. We developed and validated a diagnostic risk prediction model from common clinical factors to predict a term neonate’s probability of PAIS. Methods: A diagnostic prediction model was developed using multivariable logistic regression. Common pregnancy, delivery, and neonatal clinical factors were collected across four registries. Variable selection was based on peer-reviewed literature. Participant inclusion criteria were term birth and no underlying predisposition to stroke. The primary outcome was discriminative accuracy of the model predicting PAIS, measured by the concordance (C-) statistic. Results: 2571 participants (527 cases, 2044 controls) were eligible for analysis. Nine variables were included in the model – maternal age, tobacco exposure, recreational drug exposure, pre-eclampsia, chorioamnionitis, maternal fever, emergency c-section, low 5-minute Apgar score, and sex – to predict the risk of PAIS in a term neonate. This model demonstrated good discrimination between cases and controls (C-statistic 0.73) and model fit (Hosmer-Lemeshow p=0.20). Conclusions: Clinical variables can be used to develop and internally validate a model of PAIS risk prediction. Identifying high-risk neonates for early screening and treatment could reduce lifelong morbidity.

This survey explored access to British Columbia (BC) hospital-based neurorehabilitation outpatient programs (HB-NROPs). Fifteen rehabilitation-focused healthcare providers were interviewed. Wait times for HB-NROPs were up to 3 months for initial appointments, and inclusion criteria were variable. Two HB-NROPs had occasional access to specialized physicians. Informal communication methods were preferred modes of collaboration. BC HB-NROPs varied in access, use of interdisciplinary care, and outcome measures used to measure performance. The lack of coverage for nonphysician services may be a barrier to collaborative care in the community. Future projects should explore solutions to improve funding and equal access to BC HB-NROPs.

This article discusses subspecialty Canadian neurosurgeons’ perceptions of entrustable professional activities (EPAs) assessments and variabilities prior to the implementation of the Competence by Design (CBD) system in Canada. Vascular neurosurgeons were asked to reflect on how they would evaluate and give feedback to neurosurgery residents concerning the EPA “Performing surgery for patients with an intracranial aneurysm.” Interviews were transcribed and analyzed using a deductive approach. Themes were derived from these interviews and reflected on the subjectivity and biases present in the EPA assessment forms. Indeed, faculty may require more training in the transitioning to a CBD evaluation system.

Globally, internal medicine (IM) residents often feel they lack the knowledge and skills to approach patients presenting with neurologic issues. We conducted a multiple method needs assessment to determine the feasibility of a novel neurology flipped classroom (FC) curriculum for internal medicine residents. Our primary findings include participants: (1) finding neurology a useful rotation; (2) feeling uncomfortable with the neurological examination; and (3) endorsing flipped classroom as a potential alternative but with significant barriers. Our findings elucidate upon the various extrinsic/intrinsic motivators for resident education and illustrate the need to re-examine the way in which neurology is being taught to off-service residents.