Background: Observational studies have reported an association between childhood obesity and a higher risk of multiple sclerosis (MS). However, the difficulties to fully account for confounding and long recall periods make causal inference from these studies challenging. The objective of this study was to assess the contribution of childhood obesity to the development of MS through Mendelian randomization, which uses genetic associations to minimize the risk of confounding. Methods: We selected 23 independent genetic variants strongly associated with childhood body mass index (BMI) in a genome-wide association study (GWAS) which included 47,541 children. The corresponding effects of these variants on risk of MS were obtained from a GWAS of 14,802 MS cases and 26,703 controls. Standard two-sample Mendelian randomization methods were performed, with additional sensitivity analyses to assess the likelihood of bias from genetic pleiotropy. Results: The inverse-variance weighted MR analysis revealed that one standard deviation increase in childhood BMI increased odds of MS by 26% (odds ratio=1.26, 95% confidence interval 1.10-1.45, p=0.001). There was no significant heterogeneity across the individual estimates. Sensitivity analyses were consistent with the main findings and provided no evidence of pleiotropy. Conclusions: This study provides genetic support of a role for increased childhood BMI in the development of MS.

Background: Mutations in the gene encoding Ubiquilin-2 (UBQLN2) are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). UBQLN2 plays a central role in ubiquitin proteasome system (UPS) and UBQLN2 up-regulation exacerbates TDP-43 cytoplasmic aggregates. Methods: To analyse interaction between UBQLN2 and TDP-43 and to produce a relevant ALS animal model, we have generated a new transgenic mouse expressing UBQLN2P497H under the neurofilament heavy (NFH) gene promoter. The mice were then bred with our previously described TDP-43G348C mice to generate double transgenic mice. Results: With low expression UBQLN2, the double transgenic mice developed TDP-43 cytosolic accumulations in motor neurons starting at 5 months of age. These double transgenic mice exhibited motor neuron loss, muscle atrophy, as well as motor and cognitive deficits during aging. The microglia from double transgenic mice were hyperresponsive to lipopolysaccharide (LPS). In vivo and in vitro analyses suggested that extra UBQLN2 proteins can exacerbate cytoplasmic TDP-43 accumulations by competing with the UPS for binding to ubiquitin. Thus, increasing the pool of ubiquitin promoted the UPS function with ensuing reduction of TDP-43 aggregation. Conclusions: In conclusion, the double transgenic UBQLN2P497H; TDP-43G348C mice provides a unique mouse model of ALS/FTD with enhanced TDP-43 pathology that can be exploited for drug testing.

Background: Axial myopathy is a rare neuromuscular disorder of variable etiology characterised by preferential involvement of the paraspinal muscles. We reviewed clinical features of patients with axial myopathies and the diagnostic yield of myositis-associated antibodies and targeted next generation sequencing panels. Methods: We performed a retrospective review of patients presenting with axial myopathy at the Montreal Neurological Hospital from 2011-2018. Data collection included clinical presentation, disease course, results of electromyography, imaging, laboratory and genetic testing, and histopathology on muscle biopsy. Results: Twenty-five patients were identified. Initial manifestation of axial weakness was head drop (15), camptocormia (8), and rigid spine (2). Autoimmune myositis was diagnosed in 9 patients, seropositive in 7 out of 7 tested for myositis-associated antibodies. Genetic testing was consistent with oculopharyngeal muscular dystrophy in one patient and RYR-1 (ryanodine receptor 1) related core myopathy in another. Local radiotherapy or spine surgery preceded the onset of axial weakness in 1 and 6 patients, respectively. Muscle biopsies were available in 17 patients and revealed myopathic changes (16), inflammatory changes (6), and myopathy with vacuoles (3). Conclusions: Recent advancements in genetic and antibody testing, combined with paraspinal muscle biopsy, allow for more precise classification and identification of potentially treatable axial myopathies.

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.

Background: Diffusion-tensor imaging (DTI) tractography is commonly used in neurosurgical practice, but is largely limited to the preoperative setting. This is due primarily to image degradation caused by susceptibility artifact when conventional single-shot (SS) echo-planar imaging DTI is acquired for open cranial, surgical position intraoperative DTI (iDTI). A novel, artifact-resistant, readout-segmented (RS) DTI has not yet been evaluated in the intraoperative MRI (iMRI) environment. Our objective was to evaluate the performance of RS-DTI versus SS-DTI for intraoperative white matter imaging. Methods: Pre- and intraoperative 3T, T1-weighted and DTI (RS-iDTI and SS-iDTI) in 22 adults undergoing intraaxial iMRI resections (low-grade glioma: 14, 64%; high-grade glioma: 7, 32%; cortical dysplasia: 1). Regional susceptibility artifact, anatomical deviation relative to T1WI, and tractographic output were compared between iDTI sequences. Results: RS-iDTI resulted in less regional susceptibility artifact and mean anatomic deviation (RS-iDTI: 2.7±0.2 mm versus SS-iDTI 7.5±0.4 mm; p<0.0001). Tractographic failure occurred in 8/22 (36%) patients for SS-iDTI whereas RS-iDTI permitted successful reconstruction in 4 of these 8. Maximal tractographic differences between DTI sequences were substantial (mean 9.7±5.7 mm). Conclusions: Readout-segmented EPI enables higher quality and more accurate DTI for surgically relevant tractography of major white matter tracts in intraoperative, open cranium, neurosurgical applications at 3T.

Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.

Background: Patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (MG) unresponsive to conventional treatment experience greater disease burden than responsive patients. This is partly due to exacerbations, which may result in significant healthcare resource utilization. Eculizumab is well tolerated and gives clinically meaningful benefits in these patients. We evaluated the effect of long-term eculizumab treatment on exacerbations, hospitalizations and rescue therapy in the REGAIN study and its open-label extension. Methods: Exacerbations were defined as clinical worsening/deterioration, MG crises or rescue therapy usage; pre-study exacerbations/hospitalizations were defined from patient records. Event rates adjusted for patient-years were calculated for all patients in the pre-study year, patients receiving placebo during REGAIN, and patients receiving eculizumab during REGAIN and its open-label extension (median exposure, 27.5 months [range, 22 days–42.8 months]); rates were compared using a Poisson regression model. Results: Eculizumab treatment reduced exacerbations by 65% (p=0.0057), hospitalizations by 71% (p=0.0316) and rescue therapy use by 66% (p=0.0072) versus placebo. Eculizumab treatment reduced exacerbations by 74% and hospitalizations by 83% (both p<0.0001) versus the pre-study year. Conclusions: Long-term eculizumab treatment reduces disease burden and healthcare resource utilization, demonstrating continuing improvements in clinical endpoints that lead to additional meaningful outcomes for patients with AChR+ generalized MG. (NCT01997229, NCT02301624).

Background: There is an unmet need for blood-based biomarkers that can reliably detect MS disease activity. Serum Biomarkers of interest includ Neurofilament-light-chain (NfL), Glial-fibrillary-strocyte-protein(GFAP) and Tau. Bone Marrow Transplantation (BMT) is reserved for aggressive forms of MS and has been shown to halt detectable CNS inflammatory activity for prolonged periods. Significant pre-treatment tissue damage at followed by inflammatory disease abeyance should be reflected longitudinal sera collected from these patients. Methods: Sera were collected from 23 MS patients pre-treatment, and following BMT at 3, 6, 9 and 12-months in addition from 33 non-inflammatory neurological controls. Biomarker quantification was performed with SiMoA. Results: Pre-AHSCT levels of serum NfL and GFAP but not Tau were elevated compared to controls (p=0.0001), and NfL correlated with lesion-based disease activity (6-month-relapse, MRI-T2 and Gadolinium-enhancement). 3-months post-treatment, while NfL levels remained elevated, Tau/GFAP paradoxically increased (p=0.0023/0.0017). These increases at 3m correlated with MRI ‘pseudoatrophy’ at 6-months. NfL/Tau levels dropped to that of controls by 6-months (p=0.0036/0.0159). GFAP levels dropped progressively after 6-months although even at 12-months remained higher than controls (p=0.004). Conclusions: NfL was the closest correlate of MS disease activity and treatment response. Chemotherapy-related toxicity may account for transient increases in NfL, Tau and MRI brain atrophy post-BMT.

Background: Primary Progressive Aphasia (PPA) involves an isolated impairment of language function at disease onset. The cholinergic system is implicated in language and cholinergic deficits are seen in brains of individuals with PPA. One major source of cholinergic innervation is the nucleus basalis of Meynert (NBM) within which lies the nucleus subputaminalis (NSP). We quantified cholinergic neurons in the NBM and NSP of PPA and controls. Also explored was whether individuals with PPA who subsequently developed different clinical and neuropathological profiles, showed similar cholinergic deficits in the NSP. Methods: Cytoarchitecture of the basal forebrain was studied using Nissl staining in control (n=5) and PPA (n=5) brains. Choline acetyltransferase immunohistochemical staining labelled cholinergic neurons, quantified using Neurolucida software. Results: Compared to matched controls, PPA showed reduction of cholinergic neurons in the NBM, t(4) = 4.224, p = 0.013; Cohen’s d=1.89 and the NSP, t(4) = 4.013, p = 0.016; Cohen’s d= 1.79. The average percent of cholinergic neuronal loss was higher in the NSP (64.66%) compared to NBM (17.66%). Conclusions: Regardless of underlying pathology, all cases presenting with PPA showed marked loss of cholinergic neurons in the NSP providing further evidence for the importance of this nucleus in language function.

Background: There is currently no accepted classification of recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus and develop a clinical and pathophysiological classification for recessive ataxias. Methods: The work of this task force was based on a scoping systematic review of the literature that identified recessive disorders characterized primarily by a cerebellar motor syndrome and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. Results: We identified 59 disorders that are classified as primary recessive ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. The primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia. We also identified a list of 48 complex multisystem disorders in which ataxia is a secondary feature. Conclusions: This classification is based on a scoping systematic review of the literature and results from a sconsensus among a panel of international experts. It promotes a unified understanding of recessive cerebellar disorders for clinicians and researchers.

Background: We recently demonstrated that late functional improvement between 3-12 months post-stroke occurs in about one-fourth of patients with ischaemic stroke. It is unknown whether this improvement is associated with better long-term clinical or health-economic outcomes. Methods: In a prospective, population-based cohort of 1-year ischaemic stroke survivors (Oxford Vascular Study;2002-2014), we determined changes in functional status (modified Rankin Scale[mRS], Rivermead Mobility Index[RMI], Barthel Index[BI]) from 3-12 months post-stroke. We examined the association of late improvement (by ≥1 mRS grades, ≥1 RMI points, and/or ≥2 BI points) with 5-year mortality, institutionalization (Cox regressions), and health/social-care costs (generalized linear models), adjusted for age/sex/3-month disability/stroke subtype. Results: Among 1,288 1-year survivors, 1,135 had 3-month mRS>0, with 319(28.1%) demonstrating late improvement. 1-year survivors with late mRS improvement had lower 5-year mortality (aHR:0.68,95%CI 0.51-0.91,p=0.009), institutionalization (aHR:0.48,0.33-0.72,p<0.001), and costs (margin -$17,369,-25,271 to -9,469,p<0.001). These associations remained on excluding patients with recurrent strokes during follow-up (e.g. 5-year death/institutionalization aHR:0.59,0.44-0.79,p<0.001) and on examining late improvement per RMI and/or BI (e.g. 5-year death/institutionalization aHR:0.67,0.53-0.84,p=0.001). Conclusions: Late functional improvement post-stroke is associated with lower 5-year mortality, institutionalization, and costs. These findings should motivate patients and clinicians to maximize late recovery and encourage payers to consider access to rehabilitative services for at least 1-year post-stroke.

Background: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy characterized by abrupt sleep-related hypermotor seizures (SRHS) with complex semiology. Although difficult to localize within the frontal lobe recent studies using intracerebral EEG recordings have suggested the existence of four distinct semiology patterns (SP) organized in a rostro-caudal manner. It remains unclear however if these SP are clinically useful. Methods: We aimed to estimate the inter-rater reliability (IR) of classifying SP in SHE amongst epilepsy and sleep medicine experts. Following a short training session, ten experts were asked to review and classify 40 videos of SRHS in patients with confirmed SHE. IR was calculated using Kappa statistics. Results: SP1 and SP4, who are at the opposite ends of the SHE semiology spectrum, had substantial IR (0.82 and 0.67, respectively). Meanwhile, SP2 and SP3 showed fair agreement (0.25 and 0.35, respectively) and represented the major source of variance, with a small difference favouring epilepsy experts. Conclusions: Amongst epilepsy and sleep medicine experts, IR of classifying SRHS into four SP was only mildly satisfactory. SP1 and SP4 were shown to be easily recognizable while SP2 and SP3 were frequently confounded. Improvements in SP recognition are needed before widespread clinical use.

Background: To evaluate efficacy, safety, and tolerability of ubrogepant, an oral CGRP receptor antagonist, for acute treatment of a single migraine attack. Methods: Multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack, phase 3 study (NCT02828020). Patients randomized 1:1:1 to placebo, ubrogepant 50mg, or ubrogepant 100mg had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints: pain freedom 2 hours post initial dose and absence of most bothersome migraine-associated symptom (MBS). Results: 1672 patients were randomized (safety population: n=1436; mITT population: n=1327). Mean age: 40.7 years; white (82.4%); female (87.5%). A significantly greater percentage of ubrogepant- than placebo-treated patients achieved pain freedom 2 hours post initial dose (50mg: 19.2%, adjusted P=0.0023; 100mg: 21.2%, adjusted P=0.0003; placebo: 11.8%). A significantly greater percentage of ubrogepant patients achieved absence of MBS (50mg: 38.6%, adjusted P=0.0023, 100mg: 37.7%, adjusted P=0.0023; placebo: 27.8%). The adverse event (AE) profile of ubrogepant was similar to placebo. The most common AEs (incidence ≥2% in any treatment group) within 48 hours of initial or optional second dose were nausea, somnolence, and dry mouth (all with incidence <5%). Conclusions: Both co-primary endpoints were met, with clinically meaningful effects on migraine headache pain and MBS. Ubrogepant was well tolerated, with no identified safety concerns.

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: Preterm infants are at risk for adverse neurodevelopmental outcomes, however studies examining preterm twins are limited. The aim of this study was to examine whether preterm monozygotic (MZ) and dizygotic (DZ) twins have similar morbidities and long-term neurodevelopmental outcomes. Methods: From a cohort of 225 preterm neonates studied with MRI, 24 MZ and 52 DZ twins were included. Outcomes at 1.5-years, 3-years and 4.5-years were assessed with the Bayley-III, Movement Assessment Battery for Children and Wechsler Preschool and Primary Scale of Intelligence. Results: Twin pairs had substantial concordance for retinopathy of prematurity but only moderate-fair concordance for bronchopulmonary dysplasia, infection and brain injury. Differences in cognitive and language scores were stable over time, while motor differences increased. Discordant twins had significantly lower gestational age [Mean1(SD)=26.7(1.38); Mean2(SD)=29.1(2.1); P<0.001] and birth weight [Mean1(SD)=892.2(291.2); Mean2(SD)=1208.0(289.4); P=0.001] and a higher incidence of bronchopulmonary dysplasia and retinopathy of prematurity. In discordant twins, cognitive and language score differences decreased over time while motor differences increased. Conclusions: Preterm twin pairs have similar neurodevelopmental outcomes through early childhood despite poor concordance for perinatal illness. Discordant twins were born earlier and had more morbidities. Increasing concordance in cognitive and language outcomes over time may reflect the positive impact of early intervention programs.

Background: Continuous electroencephalographic (cEEG) monitoring is essential to diagnosing non-convulsive seizures (NCS), reported to occur in 7-46% of at-risk critically ill patients. However, cEEG is labour-intensive, and given scarcity of resources at most centres cEEG is feasible in only selected patients. We aim to evaluate the clinical utility of cEEG at our centre in order to optimize further cEEG allocation among critically ill patients. Methods: Using a clinical database, we identified critically ill children who underwent cEEG monitoring in 2016, 2017 and 2018. We abstracted underlying diagnoses, indication for cEEG monitoring, cEEG findings, and associated changes in management. Results: Over this three year period, 928 cEEGs were performed. Among the 100 studies analyzed to date, primary indications for monitoring were characterization of events of unclear etiology (32%), diagnosis of NCS (30%), and monitoring of therapy for seizures (17%). Seizures were captured in 31% of patients (22% subclinical only, 5% electroclinical only, 4% both), which resulted in a treatment change in 90% of cases. Non-epileptic events were captured in 26% of patients. Conclusions: cEEG yielded clinically meaningful information in 57% of cases, frequently resulting in management changes. Subgroup analyses by cEEG indication and ICU location will be presented.

Background: Migraine is a prevalent and disabling condition with limited understanding in the developing brain. Adults with chronic migraine show structural alterations in pain and sensory processing regions. Similar data is lacking in children and required for early intervention. Methods: Case-control feasibility study assessing structural brain differences between adolescents with chronic migraine and healthy controls using 3T Siemens structural volumetric MRI analysis. Fifteen subjects with chronic migraine were compared to 25 age and sex matched healthy controls. Non-parametric statistics performed (Kruskal-Wallis). Results: Migraine subjects had reduced volumes in total brain (grey and white matter) (KW p <0.03), total thalamus (KW p <0.01) and hippocampal regions (KW p <0.03). Unilateral (right) cerebellar grey matter volumes were significantly reduced in migraine subjects versus controls (KW p<0.05). No significant differences were found in other regions, including basal ganglia, cortical grey matter and brainstem. Conclusions: Total brain, hippocampal and thalamic volumetric reductions are seen in adolescents with chronic migraine. The regions identified are involved in migraine pathogenesis. This volumetric imaging study should improve understanding of the causes and effects of pediatric migraine.

Background: Growing evidence has that a suggested that mental health strongly influences quality of life (QoL) in adolescents with epilepsy. In addition, research has suggested that these mental health issues are associated with increased seizure burden and worsened health outcomes. Despite this, and the elevated rate of mental health issues in this population, seizure control tends to be the dominant or sole concern for treating physicians. Methods: In order to look at potential predictors of QoL in adolescents we looked at seizure related data, demographic variables, and comorbid conditions in 70 adolescents with epilepsy aged 14 to 18 (M= 16.3l; 37 males, 33 females) enrolled into an epilepsy transition clinic. Results: Regression analysis found that mental health remained a significant and independent predictor of QoL even when other significant seizure related variables were accounted for (t(58)= -3.44, p= .001). Furthermore, when looking at the individual subscales of patient QoL (e.g., memory, social support, stigma), mental health was consistently found to be the strongest correlate. Conclusions: These results demonstrate that in order to ensure the best outcomes for transition-aged adolescents with epilepsy, it is important to not only manage and treat seizures, but also to assess and treat mental health issues.

Background: Cerebellar atrophy is characterized by loss of cerebellar tissue, with evidence on brain imaging of enlarged interfolial spaces compared to the foliae. Genetic ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. We investigated the prevalence in Canada and the diagnostic yield of whole exome sequencing (WES) for this group of conditions. Methods: Between 2011 and 2017, WES was performed in 91 participants with cerebellar atrophy as part of one of two national research programs, Finding of Rare Genetic Disease Genes (FORGE) or Enhanced Care for Rare Genetic Diseases in Canada (Care4Rare). Results: A genetic diagnosis was established in 58% of cases (53/91). Pathogenic variants were found in 24 known genes, providing a diagnosis for 46/53 participants (87%), and in four novel genes, accounting for 7/53 cases (13%). 38/91 cases (42%) remained unsolved. The most common diagnoses were channelopathies in 12/53 patients (23%) and mitochondrial disorders in 9/53 (17%). Inheritance was autosomal recessive in the majority of cases. Additional clinical findings provided useful clues to some of the diagnoses. Conclusions: This is the first report on the prevalence of genetic ataxias associated with cerebellar atrophy in Canada, and the utility of WES for this group of conditions.

Background: Lumbar puncture (LP) is a low-risk procedure performed on pediatric patients for a variety of indications. There are no published studies of the nature of the concerns of parents in North America, and no studies examining a process to improve pediatric lumbar puncture consent. Methods: 72 patient-parent dyads were enrolled in a randomized control trial to receive standard consent with or without an educational video. A survey was provided to determine parent self-rated understanding of the procedure, their perception of its safety, their perception of the painfulness and their overall comfort with their child undergoing LP. In addition, demographic characteristics and qualitative information about parent concerns were collected. Results: Viewing the video significantly increased parent understanding of the procedure (p=0.015) and their perception of its safety (p=0.021) compared to controls. Parent comfort with the procedure increased after viewing the video (p = 0.002). Variability of answers was reduced in the video group (p = 0.03). Parents’ top three concerns were pain, infection, and neurologic injury. Conclusions: Pediatric lumbar puncture consent can be significantly improved with a short educational video to address the parental concerns and standardize consent.