Background: Obtaining early intervention services is crucial for improving outcomes in children with neurodevelopmental disorders (NDDs) such as Autism or Attention Deficit/Hyperactivity Disorder. Identifying barriers in accessing services in the healthcare system is necessary to optimize the Patient and Family-Centered Care approach. Methods: Parents of children with an NDD co-occurring with attention deficits were recruited from the Neurodevelopmental Attention Clinic at the Alberta Children’s Hospital. Parents completed a semi-structured interview and the Barriers to Accessing Services (BAS) questionnaire. Results: Nine families participated representing 10 children. Interviews were evenly spread between biological mothers and fathers. All children had attention deficits; 4 children were also diagnosed with Autism and 5 with “other” neurologic conditions. The two barriers most identified by families (67%) through the BAS questionnaire were “Didn’t know where to find help” and “Steps to seek help are too overwhelming”, consistent with information obtained in the interview. Conclusions: Children with an NDD and attention deficits often have complex medical needs. Parents have identified challenges initiating, and navigating the many steps involved to secure services. We will collect information from more families to determine how services for children with complex medical needs can become more accessible.

Background: We explored the profile of children with cerebral palsy (CP) secondary to intrapartum asphyxia (IAP), who were treated with therapeutic hypothermia (TH). We compared neonatal characteristics between children treated with TH with a mild vs severe CP. Methods: We collected perinatal and outcome measures of children treated with TH for IAP. We searched the literature for characteristics of children prior to TH to compare to our cohort. We subdivided our cohort into mild vs. severe CP and compared neonatal characteristics to identify predictors of severe phenotype. Results: We found more children with severe (19/30) compared to mild CP (11/30). Post-TH era children leaned towards a more severe phenotype compared to prior to TH. Children with severe CP had significantly higher mean birth weight, lower 5- and 10-minute Apgars, and more often white matter with associated deep gray matter injury or near-total injury pattern on MRI compared to the mild phenotype group (all p<0.05). Conclusions: Our data leaned to a more severe CP in cooled children compared to pre-TH. Birthweight, 5- and 10-minute Apgars and MRI findings were significantly different between our mild vs severe group. Our findings can guide clinicians how to better weigh these factors when counseling parents in the neonatal period.

Background: While seizures have adverse neurological effects, the prescribed antiseizure medications (ASMs) may also have a negative impact on neonatal brains and contribute to detrimental neurodevelopmental outcomes. The objectives were to evaluate: 1) the impact of implementing a neonatal seizure treatment protocol in 2016; 2) the influence of ASM duration and other clinical factors on seizure recurrence and epilepsy onset. Methods: Retrospective chart review of 139 term newborns born between 2013 and March 2021 admitted at Sainte-Justine University Center Hospital with acute symptomatic seizures. Associations were assessed using Student T-test and Fisher exact test. Results: We did not observe significant change in the number of ASMs prescribed for acute seizure control (33% required 33 ASMs before vs 22% after 2016) nor significant change in frequency of prescription of ASM at discharge over time. ASM continuation at discharge was not associated with seizure recurrence (p=0.14, OR 2.14, 95%CI 0.78-5.86) or epilepsy (p=0.78, OR 1.32, 95% CI 0.45-3.90). Epilepsy occurred in 15 (12%) of children between 15 days to 72 months of age. Conclusions: No association was found between ASM maintenance at discharge following acute symptomatic neonatal seizures and the occurrence of epilepsy. Discontinuation of ASMs should be considered prior to discharge.

Background: mTBI is the most common type of head injury among children but diagnosing and managing symptoms are challenging due to heterogeneity. This study used multi-modal analysis to examine how acute mTBI symptoms transition to chronic deficits. Methods: Subjects included a cohort with mild TBI (n=40, 8-18 years old) and age/sex-matched controls (n=27). All participants received symptom assessment, neuropsychological evaluation, ERP assessment, neuroimaging, and serum cytokine analysis. Results were analyzed individually and in multi-modal models to identify important outcome predictors. Results: mTBI resulted in higher symptom burdens compared to controls. There were no group differences in measures of balance, ERP, FA, or MD. Female mTBI participants had lower CNSVS Neurocognition Index scores (p=0.0401) and faster reaction times (p=0.0385) than controls. Repetitive mTBI males had faster psychomotor speed than symptomatic mTBI males (p=0.0260). CTACK levels were higher in female mTBI groups (p= 0.0043), SCGF- levels were lower in male mTBI groups (p=0.0486), and MDC levels were lower in female mTBI groups (p=0.0377) compared to controls. Multi-modal models revealed key predictors from all modalities, despite most measures producing non-statistically significant results in individual analyses. Conclusions: Multi-modal analysis may afford the opportunity to delineate complex mTBI pathology and provide better identification of biomarkers than unimodal analysis.

Background: Clinical outcomes following childhood arterial ischaemic stroke (AIS) depend on age at the time of stroke, infarct size and location. However, other important variables including health inequity and stroke onset to arrival times remain inadequately addressed. This study reported trends in health inequity and stroke onset to arrival times along with proximity to a stroke centre in Canada. Methods: Childhood AIS patients (N=234) with stroke onset between 2004-2019 at a Level 2 (comprehensive) stroke centre were included. Measures of material deprivation included household income, education, single-parent families, and housing quality. Patients were stratified into 3 cohorts (by date of stroke onset) and postal codes were categorized as minimal, moderate, or most deprived neighbourhoods. Results: Over the 16-year period, an increasing number of patients arrived from the most deprived neighbourhoods. Although, there was no significant association between material deprivation and stroke onset to arrival time, an increasing number of patients presented within 6 hours of stroke onset (χ2 = 13.8, p = 0.008). Furthermore, most patients arrived from urban neighbourhoods. Conclusions: The faster stroke onset to arrival trend is encouraging, however, material deprivation trends are concerning. Thus, future studies exploring post-stroke outcomes should consider material deprivation, stroke onset to arrival times, and geographical proximity.

Background: Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are neurodegenerative disorders characterized by progressive structural and functional loss of specific neuronal populations, protein aggregation, insidious adult onset, and chronic progression. Modeling these diseases in animal models is useful for studying the relationship between neuronal dysfunction and abnormal behaviours and for screening therapies. Methods: We conducted a comprehensive descriptive review of the numerous animal models currently available to study these three diseases with a focus on their utilities and limitations. Results: A vast range of genetic and toxin-induced models have been generated. Our review outlines how these models differ with regards to the genetic manipulation or toxin used and the brain regions lesioned, describes the extent to which they mimic the neuropathological and behavioral deficits seen in the human conditions, and discusses the advantages and drawbacks of each model. Conclusions: We recommend the adoption of a conservative approach when extrapolating findings based on a single animal model and the validation of findings using multiple models. Investing in additional preclinical studies before embarking on more expensive human trials will improve our understanding of the neuropathology underlying neuronal demise and enhance the chances of identifying effective therapies.

Background: Smoking is the leading cause of preventable morbidity worldwide and therefore developing effective smoking cessation strategies is a public health priority. However, what brain networks support maintenance of smoking cessation in the long term remains unexplored. Methods: We analyzed the baseline resting-state fMRI data acquired in 23 smokers (Mage = 61.52 ± 3.7) who were followed longitudinally in a cohort of cognitively normal older adults. Self-reported smoking status and amount were recorded at baseline and repeated after 4 years. We investigated the effect of smoking behaviour change on functional brain connectivity using seed-to-voxel approach. We examined a-priori regions of interest (ROIs) including the reward network (ventromedial prefrontal cortex (vMPFC) and ventral striatum) and the right insula. These ROIs are promising target mechanisms given prior behavioural research linking it to smoking cessation. Results: Our results revealed that reduced smoking was associated with reduced connectivity between ventral striatum and middle frontal gyrus and enhanced connectivity between right insula and middle temporal gyrus (voxel p <0.001, cluster p<0.05 FDR corrected). However, change in smoking did not reveal any significant effects in the vMPFC. Conclusions: Our findings suggest that successful smoking behaviour change is associated with altered reward network and insular functional connectivity in the long term.

Background: Responsive Neurostimulation (RNS) has proven efficacy in the treatment of medically resistant epilepsy as an intracranial system that detects, records and treats seizures automatically. No information exists pertaining to artifact characteristics of RNS findings in scalp EEG. Methods: A 30 year-old female was diagnosed, using intracranial electroencephalography (iEEG), with refractory bi-insular epilepsy, of unknown cause. Due to her large number of focal unaware non-motor seizures and frequent seizures with progression to bilateral tonic-clonic, she was implanted with bi-insular Responsive Neurostimulation (RNS). Results: Results: During scalp EEG recordings, a prominent artifact was seen corresponding to an automatized discharge suspectedly evoked by the RNS trying to minimize the frequent epileptiform activity in her case. Figure 1 and 2 depict these findings. Conclusions: The artifact seen by the RNS in scalp EEG has not been previously described in scientific literature. These findings must be identified to better characterize the role of the RNS in EEG and treatment of seizure activity visible on scalp recordings.

Background: Background: Cortical stimulation (CS) as a part of presurgical investigations in patients undergoing implantation of depth electrodes (SEEG) is a growing practice in some Comprehensive Epilepsy Centers. After-discharges (AD) are useful to determine epileptogenic tissue within or outside the epileptogenic network. Classification of afterdischarges was proposed by Blume using subdural recordings(1); its utility in SEEG is unknown. Methods: Methods: Single center, retrospective study that included patients with SEEG that underwent CS in the Epilepsy Monitoring Unit. Demographic characteristics were explored and Blume’s proposed AD classification was used to determine whether or not the CS changed surgical outcomes. Results: Results: From January 2015 to June 2021, a total of 177 patients were implanted with SEEG and analyzed. 95 patients had CS and 91 had AD. Morphologies found were: Rhythmic waves in 4 (0.04%), Rhythmic waves evolving into spikes in18 (19%), Polyspike bursts in 14 (15%), Spike-waves in 28 (30%), and sequential spikes in 18 (19%). 12/14 (86%) patients with Spike-waves had Engel I outcome; Engel class IV patients were more likely to have an evolution of morphology and frequency of ADs in 3 patients(75%). Conclusions: Conclusions: The most frequent morphology of ADs seen was spike-waves. AD morphology and duration may predict post-operative seizure outcomes.

Background: Background: Language determination is a pivotal part of presurgical investigations. Presurgical cortical stimulation (CS) with language mapping (LM) in patients with intracranial recordings (SEEG) is a growing practice in some Comprehensive Epilepsy Centers. Methods: Methods: This retrospective, single center study included patients implanted with SEEG that underwent CS for LM in our Epilepsy Monitoring Unit. We describe frequencies, demographic characteristics of these patients and whether or not CS with LM was useful. Results: Results: From January 2015 to June2021, a total of 177 patients were implanted with SEEG and analyzed. 95 patients had CS and 44 of these had CS with LM. The mean age was 33 (ranging from 15-70). During LM, anomia was induced in 26 (58%), speech arrest in 22 (49%), paraphasic errors in 13 (29%), and hesitation in 9 (20%). LM results were recorded as influencing surgical decision in 7 (16%) patients, 4 (9%) did not undergo surgery due to expected language deficits and 3 (7%) proceeded with surgery due to an acceptable risk of language deficit. Conclusions: Conclusions: Cortical stimulation language mapping is useful for decision-making in presurgical evaluation and should be encouraged whenever involvement of language is suspected when determining the epileptogenic zone.

Background: Focal spasticity affects up to 1 in 3 residents in long-term care (LTC), with potentially disabling consequences. Data are limited on access to care for patients requiring botulinum toxin (BoNT) treatment in LTC. Methods: This retrospective, observational, real-world study was conducted using the Ontario Drug Benefit claims database. Patients with ≥1 medical claim for BoNT for focal spasticity treatment were selected, and those residing in LTC were further identified. Data were analyzed for the utilization (2000–2019), treatment rate, and time-to-treatment with BoNT in LTC residents (2015–2019). Results: Over a 10-year period, the number of patients receiving BoNT for spasticity increased 7-fold and the proportion of patients residing in LTC versus community increased from 43% (2010) to 52% (2019). Of the LTC residents eligible for BoNT treatment, 33% received BoNT in 2015 compared with 63% in 2019. Injections/patient/year increased from 1.9 (2010) to 3.1 (2017). Following LTC admission, median time to first injection was 2.9 years. Conclusions: In this study, approximately 40% of eligible LTC residents in Ontario were not receiving BoNT treatment, and of those who were, median time to first injection was 2.9 years. Future policy considerations should prioritize uniform access to spasticity standards of care for LTC residents.

Background: Early recognition of neonatal seizures secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications, but respond well to sodium-channel blockers. We report a unique aEEG pattern in neonatal seizures caused by SCN2A and KCNQ3 pathogenic variants, as well as adding regular EEG description. Methods: International multicentre descriptive study, reporting clinical characteristics, aEEG and conventional EEG findings of 10 newborns with seizures due to pathogenic SCN2A and KCNQ3 gene variants. Results: Seizures started in the first postnatal week. Seizure semiology typically included tonic posturing with apnea and desaturation. The aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral attenuation in the EEG at onset, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. The majority of patients became seizure free upon initiation of a sodium-channel blocker. Conclusions: Neonatal seizures caused by SCN2A and KCNQ3 mutations can be recognized by a characteristic ictal aEEG pattern and clinical semiology. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium-channel blockers even before genetic test results are available.

Background: A-waves are lesser-known late responses of debated clinical significance, seen in routine motor nerve conduction studies (NCS). They are proposed to be a sensitive marker of demyelination and an early finding in acute demyelinating polyradiculoneuropathy (AIDP). We hypothesized that the presence and distribution of A-waves are discriminative markers in differentiating AIDP from axonal variants of Guillain-Barré Syndrome (GBS). Methods: We identified patients diagnosed with demyelinating and axonal forms of GBS at the Montreal Neurological Institute between 2016 and 2021. Clinical and electrophysiological data including raw NCS responses were retrospectively reviewed for 28 AIDP and 9 axonal GBS cases. Results: 20 of 28 AIDP cases had at least one A-wave in non-tibial nerves compared to 2 of 9 axonal cases. Among patients with NCS available within 2 weeks of symptom onset, 13 of 14 AIDP cases had non-tibial A-waves, compared to 0 of 6 axonal cases. Eight of 14 AIDP cases had one or more nerves with multiple A-waves within 2 weeks, compared to 0 of 6 axonal cases. Conclusions: In patients with GBS, the presence of A-waves in non-tibial nerves and of nerves with multiple A-waves are early indicators of the demyelinating variant. Early identification of GBS subtype is valuable for prognostication.

Background: Diabetes mellitus is a common cause of polyneuropathy. Despite numerous diagnostic tools such as routine electrophysiologic procedures, its early detection is challenging. This study compares a distal electrodiagnostic technique, with conventional approaches to investigate its role in confirming early polyneuropathy. Methods: Thirty-one symptomatic diabetic outpatients and 23 asymptomatic nondiabetic subjects were included in our study. We performed nerve conduction studies on the dorsal sural, medial plantar, and digital branches of the interdigital nerves to toes I, II, and III (as a new antidromic technique). All techniques were applied with the surface stimulator and pick-up electrodes. Results: Only 9 (29%) of patients had impaired routine NCSs. Interestingly, the results of interdigital nerve studies were abnormal in 17 out of 22 patients with normal routine NCSs. Also, 11 and 13 subjects had impaired medial plantar and dorsal sural nerves conduction studies, respectively. According to this method, the prevalence of detectable diabetic neuropathy increased from 46% to 83%. Conclusions: The digital sensory branches can be easily evaluated with the new antidromic SNAP technique for the early diagnosis of diabetic polyneuropathy, especially in presymptomatic and subclinical neuropathies. This method is simple, non-invasive, sensitive, and reproducible. There is no need for needle electrodes or averaging techniques.

Background: Adult neurogenesis occurs in the hippocampus and the subventricular zone. Recent evidence suggests that neurogenesis may also extend to other brain regions (hypothalamus, striatum, substantia nigra, cortex, and amygdala). Harnessing this intrinsic neurogenic potential may present a novel alternative for the replenishment of neurons lost in neurologic conditions. Methods: This descriptive review summarizes evidence supporting the classic and novel neurogenic zones present within the mammalian brain, discusses the functional significance of these new neurons, and the potential clinical applications of promoting intrinsic neurogenesis. Results: Some studies suggest new neurons originate from endogenous stem cell pools located within novel neurogenic regions while others show the migration from the subventricular zone to these regions. Regardless, adult neurogenesis is impacted by neurologic processes such as ischemia and neurodegenerative diseases and can be modulated by factors including neurotrophins, pharmacologic interventions, environmental exposures, exercise, and stem cell therapy. Conclusions: The discovery of functionally significant neurogenesis in adult brain regions has implications not only with regards to the function of these regions, but also for neuropathological conditions that affect them. Pharmacologic and stem cell-based strategies capable of promoting neurogenesis may have therapeutic potential following stroke or in the context of various neurodegenerative disorders.

Background: Mild cognitive impairment (MCI) is a concern for our aging population as it can be a pre-cursor to dementia. However, the diagnosis of MCI can be quite problematic and can come long after initial onset. Here, we sought to use a new technology we have previously validated for research – mobile electroencephalography (mEEG) – to measure brain function to see if we could rapidly detect differences in brain activity between people with and without MCI. Methods: Participants (60: mean age 65) were recruited for a control (30) and an MCI group (30). All participants were screened for MCI using standard RBANS and the MOCA assessments. Participants completed a standard n-Back assessment of working memory while mEEG data was recorded. A key feature here is that we used mEEG technology thus application of the device and the n-Back test was completed in under 10 minutes for each participant. Results: Our key finding is that we observed increased frontal mEEG theta power (brain oscillations between 4 and 7 Hz) for MCI participants relative to controls (p < 0.001). Conclusions: Importantly, our work demonstrates a potential novel rapid brain-based assessment for MCI that would afford earlier detection of disease onset.

Background: Pooled mortality has been observed to be almost threefold among people with epilepsy (PWE). Among PWE, epilepsy related deaths (including sudden death in epilepsy (SUDEP)), are commoner than other causes. Among these, around 16-36% are SUDEP, of which 80% events occur during sleep. SUDEP risk is most measured using the SUDEP Risk Inventory. To prevent SUDEP and reduce epilepsy related mortality, we need a better understanding, not only of the components of this screening inventory, but also additional clinical and neurophysiologic parameters that might be commoner among PWE and potentially associated with higher mortality risk. Methods: Patients diagnosed with active epilepsy over the last 3 years will form the study population, categorized into two groups: PWE with a comorbid sleep disorder, and PWE without diagnosis of a sleep disorder. Descriptive statistics will be used to report clinic and neurophysiologic characteristics of subjects enrolled. Results: We hypothesize that there is a significantly increased prevalence of sleep comorbidity among people with epilepsy compared to the general population. Poorer sleep quality could potentially have an association with higher mortality risk among epilepsy patients, Conclusions: We hope to identify and to add sleep factors such as primary sleep disorders and sleep disturbances to already established SUDEP-7 parameters.

Background: Precision medicine for multiple sclerosis (MS) involves choosing a treatment that best balances efficacy and disadvantages such as side effects, cost, and inconvenience, based on an individual’s unique characteristics. Machine learning can be used to model the relationship between a baseline brain MRI and future new and enlarging T2 (NE-T2) lesion count to provide personalized treatment recommendations. Methods: We present a multi-head, deep neural network for making individualized treatment decisions from baseline MRI and clinical information which (a) predicts future NE-T2 lesion counts on multiple treatments and (b) estimates the conditional average treatment effect (CATE), as defined by the predicted suppression of NE-T2 lesions, between different treatment options and placebo. We validate our model on a dataset pertaining to 1817 patients from four randomized clinical trials. Results: Our model predicts favorable outcomes (< 3 NE-T2 at follow-up) with average precision 0.780-0.994 across 5 different treatment arms. It correctly identifies subgroups with different treatment effect sizes and provides treatment recommendations that improve lesion suppression while limiting the need for high efficacy treatments. Conclusions: Our framework provides accurate predictions for future NE-T2 lesion counts and personalized treatment recommendations that improve outcomes while accounting for the disadvantages of different treatment options.

Background: Intravenous immunoglobulin (IVIG) may benefit many inflammatory central nervous system (CNS) disorders based on multiple immunomodulatory effects. IVIg is being used in inflammatory CNS conditions however robust evidence and guidelines are lacking in many disorders. Over the last 5 years, the percentage of IVIg used for CNS indications within neurology almost doubled in British Columbia (BC), Canada. Clear local guidelines may guide rational use. Methods: Consensus guidelines for IVIG use for CNS indications were developed by a panel of subspecialty neurologists and the Provincial Blood Coordinating Office, informed by focused literature review. Guidelines were structured similarly to existing BC peripheral nervous system guidelines and Australian Consensus Guidelines. Utilization and efficacy will be monitored provincewide on an ongoing basis. Results: Categories of conditions for Conditionally Approved (N=11) and Exceptional Circumstance Use (N=5) were created based on level of evidence for efficacy. Dosing and monitoring recommendations were made and outcomes measures defined. Rationale for Not Indicated conditions (N=2) was included. Guidelines were distributed to BC neurologists for feedback. This system will be re-evaluated after 1 year. Conclusions: IVIG use in CNS inflammatory conditions has an emerging role. Guidelines for use and monitoring of outcomes will help improve resource utilization and provide further evidence regarding effectiveness.

Background: Isolated central nervous system lymphomas (CNS-L) has non-specific clinical presentations causing delays in diagnosis and treatment. This retrospective case series aims to characterize these challenges in the inpatient setting. Methods: Chart review of biopsy-proven CNS-L cases (n=10) presenting to Vancouver General Hospital from 2018-2020: diffuse (8/10) and intravascular (2/10) large B-cell lymphomas were included. Results: Median age was 69 years (31-83); 50% were female; 9/10 immunocompetent, 1/10 had well-controlled HIV. Neurologic symptoms at presentation: ataxia (7/10), paresis (4/10), dysphagia (4/10), dysarthria (2/10), and cognitive decline (4/10). Median time from symptom onset to admission with paresis, ataxia, dysphagia, or dysarthria was 3 days (1-14), compared to 84 days (28-384) with transient/vague symptoms. Median time from admission to biopsy was 25 days (5-148). 4/10 received steroid prior to biopsy. 1/10 had solitary lesion on MRI, 8/10 had ≥2 lesions. Diagnosed on lumbar puncture (0/10), skin biopsy (1/10), vitreous biopsy (1/10), brain biopsy (8/10), autopsy (1/10). 4/10 survived, 6/10 died; median time from admission to mortality was 133 days (61-342). Conclusions: Many factors lead to delays in diagnosis and treatment of CNS-L, including non-specific clinical presentations and time to brain biopsy for definitive diagnosis. Earlier recognition and reducing biopsy delays may help achieve earlier diagnosis.