Background: Cortical myoclonus originates at cerebral cortex, predominantly occurring on voluntary movements. Few case reports described usage of Acetazolamide (ACZ) for myoclonus. Methods: Chart review of 2 patients was performed. Literature review was conducted on myoclonus and ACZ using Pubmed. Results: 22-year-old female was diagnosed with Progressive Myoclonic Epilepsy (PME) secondary to a KCNC1 mutation. Her symptoms started at 10 years old with bilateral tonic clonic seizures (BTCS), later developing progressive ataxia and myoclonus, involving face and limbs, which worsened with stimulus and menses. Medications included Perampanel, Clonazepam and Levetiracetam, however myoclonus was still limiting. At the age of 19, ACZ 250 mg BID was started for 2 weeks around her menses. Follow up revealed significant improvement of myoclonus, resulting in better ambulation, balance and speech, sustained 2.5 years after. 67-year-old male presented BTCS at the age of 53 along with cortical myoclonus, dementia and ataxia, leading to diagnosis of PME with a mutation on IRF2BPL. Improvement of myoclonus occurred with ACZ 250 mg BID biweekly, although balance and cognition still deteriorated. Conclusions: Previous literature outlines 4 cases of action myoclonus that responded to ACZ. We believe that ACZ should be considered to treat myoclonus, especially in cases with cortical involvement and hormonal fluctuations.

Background: Radiofrequency ablation (RFA) is a minimally-invasive procedure that has been used to treat temporal lobe epilepsy (TLE), however its long-term efficacy is unknown. We aim to characterize the long-term outcomes of patients from the original series by Parrent and Blume (1999). Methods: Consecutive patients who underwent stereotactic RFA for TLE were retrospectively reviewed. Demographics, procedural details, and seizure outcomes until last follow-up were abstracted. Seizure-freedom after initial RFA treatment was estimated with Kaplan-Meier analysis. Results: 27 patients underwent RFA from 1994 to 2002. There were 14 female (52%) patients. 24 (89%) had mesial temporal sclerosis. Mean age at time of RFA was 33.1 years (range 12-45 years). 17 (63%) patients underwent left-sided RFA. 15 (56%) patients had further interventions: 4 (15%) underwent only repeat RFA, 1 (4%) had repeat RFA and anterior temporal lobectomy (ATL), and 10 (37%) underwent subsequent ATL only. Mean follow-up was 9.0 years (range 0.5-22.7 years). At last follow-up, 16 (59%) patients were seizure-free: 5 (19%) received one RFA treatment and 11 (41%) underwent additional procedures. Conclusions: Based on the original series describing the technique, stereotactic RFA for TLE is a safe, minimally-invasive procedure. The role of stereotactic RFA in the treatment of TLE remains to be determined.

Background: The drivers that activate endogenous ependymal-derived neural stem/progenitor cells (epNSPCs) remain unknown. Understanding the mechanisms that govern the biology of these cells is critical in developing a therapeutic strategy to harness their regenerative potential after injury. Methods: FoxJ1-CreER-tdTomato reporter mice were used for epNSPC lineage tracing. A conditional genetic knock-out mouse line of glutamate-subtype AMPA receptor (AMPAR) subunits in epNSPCs was generated. Electrophysiological properties were assessed using single cell patch clamp and slice culture recordings. For in vivo studies, mice underwent cervical SCI. To examine the effect of positive modulation of AMPARs, mice received the ampakine CX546 or vehicle and underwent electrophysiological testing, behavioural assessment and spinal cord extraction. Results: Glutamate excitotoxicity, a hallmark in the pathogenesis of acute SCI, drives epNSPCs activation via AMPARs. Genetic knock-out of AMPARs in epNSPCs inhibits their activation following SCI. Positive pharmacological modulation of AMPARs after SCI enhances the migration and differentiation of epNSPCs, increases neuronal sparing and improves long-term locomotor/forelimb function. SCI decreases the excitability of corticospinal tract projections, which is improved with positive AMPAR modulation. Conclusions: Glutamatergic signaling via AMPARs is an important mediator of epNSPC activation after injury. Pharmacological targeting of this mechanism can be used to enhance endogenous regeneration and improve recovery post-SCI.

Background: Migraine affects more than 1 billion people, with attacks triggered by a variety of factors. Knowledge of environmental triggers for migraine attacks is limited, and has mostly been studied via emergency room (ER) visits. There are significant barriers and delays for attending ER for migraine treatment, which create challenges for estimating causal links to environmental exposures. We assessed whether smartphone app records may have fewer barriers and reduced lags. Methods: American and Canadian participants completed an online survey about their migraine attacks, smartphone app use, and ER visits. Results: Among 308 participants, barriers to visiting ER were similar in both countries, except for financial concerns in the US. About half of participants who attended ER also recorded the attack in a diary or app. Whereas migraine patients often present to ER 7+ days after onset, records in a smartphone app dataset were created within 2 days of onset. Conclusions: Although not all severe migraine attacks are recorded by smartphone users, smartphone app records may have fewer barriers to creation and shorter time lags compared to ER visit records, making them a rich source of data for research on transient neurologic health outcomes and environmental exposures.

Background: Late onset Pompe disease (LOPD), rare autosomal recessive lysosomal storage disease, resulting from mutation in alpha glucosidase enzyme (GAA) can present even in 6th decade of life. Slowly progressive, subtle, limb girdle pattern of weakness (LGPW), with auxiliary features such as ptosis, enlarged tongue, axial rigidity, facial diplegia, variable degree of respiratory weakness is not uncommon. Hypertrophic and electrical cardiac abnormalities are well described in LOPD. Methods: We present a case of 67-year-old male presenting with proximal weakness, subtle ptosis, bilateral quadriceps and shoulder girdle atrophy, and left toe numbness. PMHx: CABG, NSTEMI. Statin use. FMHx: noncontributory. Results: EMG: L5 radiculopathy, with unexpected myopathic units in hip/pelvic/ shoulder girdle muscles with active denervation and muscle irritability. CK, CRP, SPEP, ANA, LFTs, HMG-CoA reductase: normal. GAA enzymatic activity=0.96µmol/L/hr (low), genetics: pathogenic variants in GAA gene: c.-32-13T>G and c.1194+3G>C. ECHO: severe diastolic dysfunction, restrictive left ventricular filling. PFTs: normal. Diagnosed with LOPD, started on therapy. Conclusions: LOPD remains a differential for LGPW especially in older patient population with history of cardiopulmonary features. Age-appropriate conconminant pathologies may confound the diagnostic process.Symptoms may preceed diagnosis for years.GAA enzymatic activity followed by genetic testing remains readily available and can confirm diagnosis, preventing delay of approved therapy.

Background: Continuous spike and waves during slow-wave sleep (CSWS) is a childhood-onset epileptic encephalopathy that is characterized by clinical seizures, electrical status epilepticus during sleep (ESES), and neurocognitive regression. Early intervention can preserve neurocognitive development, and vagus nerve stimulator (VNS) therapy had positive outcomes in the few previously reported case reports. We present three patients with intractable CSWS unresponsive to medications, who had a positive response to VNS therapy. Methods: Review of clinical records of three pediatric patients diagnosed with CSWS were compared for selected clinical outcomes and electrographic data both prior to and in the years following the initiation of VNS therapy. Results: Three patients now aged 13, 16 and 20 years, were treated with VNS following intolerance and a lack of response to multiple medications (5-9) for CSWS. The ketogenic diet was not an option. The CSWS resolved in all three patients, resulting in improved cognitive function. Patient 3 had resurgence of CSWS on EEG when the VNS settings inadvertently reset to the factory settings and improved with adjustment in the cycling. Conclusions: In patients who are unresponsive to medication, VNS provides an alternative option for resolving CSWS to preserve and, in some cases, potentially restore neurocognitive function.

Background: Currently there are no disease modifying treatment for Synucleinopathies including Parkinson’s disease Dementia (PDD). Carrying a mutation in the GBA gene (beta-glucocerebrosidase/ GCAse) is a leading risk factor for synucleinopathies. Raising activity GCAse lowers α-synuclein levels in cells and animal models. Ambroxol is a pharmacological chaperone for GCAse and can raise GCAse levels. Our goal is to test Ambroxol as a disease-modifying treatment in PDD. Methods: We randomized fifty-five individuals with PDD to Ambroxol 1050mg/day, 525mg/day, or placebo for 52 weeks. Primary outcome measures included safety, Alzheimer’s disease Assessment Scale-cognitive (ADAS-Cog) subscale and the Clinician’s Global Impression of Change (CGIC). Secondary outcomes included pharmacokinetics, cognitive and motor outcomes and and plasma and CSF biomarkers. Results: Ambroxol was well tolerated. There were 7 serious adverse events (SAEs) none deemed related to Ambroxol. GCase activity was increased in white blood cells by ~1.5 fold. There were no differences between groups on primary outcome measures. Patients receiving high dose Ambroxol appeared better on the Neuropsychiatric Inventory. GBA carriers appeared to improve on some cognitive tests. pTau 181 was reduced in CSF. Conclusions: Ambroxol was safe and well-tolerated in PDD. Ambroxol may improve biomarkers and cognitive outcomes in GBA1 mutation carrie.rs Ambroxol improved some biomarkerss. ClinicalTrials.gov NCT02914366

Background: There is an absence of studies evaluating longitudinal quality of life (QoL) amongst vestibular schwannomas (VS) with matched tumor and patient characteristics between treatment groups. We present novel findings of 12 yearlong follow-up of patient QoL and symptomatology outcomes in this matched cohort study. Methods: Symptomatology and 36-Item Short Form Health Survey (SF36) between 2000-2017 in VS patients managed at a single tertiary centre was conducted. Radiation (R) and active surveillance (A) groups were matched for tumor size and age against the surgery (S) group. Results: 14 A patients, 24 R patients, 49 S patients met matching and inclusion criteria. Mean age, tumor diameter and follow up was 69.1 years, 21.6mm and 12.0 years respectively. Mental component summary (MCS) scores deteriorated significantly in the radiation group (3.1 S, 3.7 A, -3.5 R, p-value 0.008). Physical component summary scores remained stable at follow up (-0.2 S, 0.00 S, -4.0 R, p-value 0.227). Various symptoms resolved statistically in surgery goup, whereas tinnitus on follow up was higher with radiation (40.8% S, 66.7% R, p-value 0.038). Conclusions: Surgery group demonstrated improvements in long term QoL with good symptom resolution, whilst radiation group demonstrated small but significant deterioration over time.

Background: The aim of our educational exhibit is to review the anatomy and pathology encountered and often overlooked of the excretory lacrimal apparatus from the lacrimal sac to the nasal fossa. Methods: We will provide an anatomical review of the various structures easily identifiable on CT and MRI and suggestions of the best imaging protocols to be used. Results: The lacrimal apparatus includes the various structures related to the production and flow of tears. In this educational exhibit we will focus on the excretory apparatus from the lacrimal sac to the nasal fossa. We will present various pathologies affecting the excretory lacrimal apparatus with attention to the specific features of each condition to facilitate an appropriate differential diagnosis. We will emphasize specific anatomical/imaging findings to help the diagnosis and propose a standardized reporting system for the Neuroradiologist and useful to the ENT surgeon. Conclusions: This educational exhibit offers a unique opportunity to review the anatomy and pathology of sometimes overlooked or forgotten structures which are however always included in our CT and MRI studies.

Background: Trapped fourth ventricle (TFV) is a rare entity that occurs when the fourth ventricle is obstructed and isolated from the normal cerebrospinal fluid (CSF) circulation. While not always symptomatic, TFV can lead to compression of the cerebellum and brainstem, with potential for serious consequences. Treatment of TFV can be challenging, with options including CSF diversion via shunts versus open or endoscopic fenestrations. In this report, we describe a case of TFV that was managed endoscopically. Methods: A seven-year-old girl with a history of myelomeningocele and hydrocephalus, presented with a change in neurological status. Imaging of the brain and spine showed syringomyelia, markedly dilated ventricles, and a TFV. An endoscopic approach was used to fenestrate the wall of the fourth ventricle. Results: While there was an early favorable outcome, the first fenestration closed over within one month, requiring a repeat endoscopic fenestration. Both procedures were complicated by transient seizures, requiring a pediatric intensive care unit (PICU) admission after the second intervention. Pre- and post-operative clinical and diagnostic imaging findings are reported. Conclusions: Endoscopic fenestration can be an effective treatment option for management of TFV. The patient, family, and treating team should be prepared to deal with acute peri-operative complications that may require PICU management.

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical condition which can be treated with surgical evacuation. A significant percentage of CSDH patients are on antiplatelet or anticoagulation therapy at baseline which may influence risk of recurrence and postoperative thromboembolic events Methods: A search was conducted in MEDLINE (1946 to April 6, 2023), Embase (1974 to April 6, 2023), and PubMed (up to April 6, 2023) on preoperative use of antiplatelet or anticoagulation therapy and outcomes following surgical evacuation of CSDH. Results: Our literature includes 14,410 patients ifrom 42 studies, with 3218 (22%) in the antiplatelet (AP) group, 1731(12%) in the anticoagulation (AC) group, and 9537 (66%) in the no antithrombotics (NA) group. The AP group had significantly higher recurrence compared to NA (OR = 1.21, 95% CI = 1.04 to 1.40, p = 0.01). The AC group also had significantly high recurrence compared to NA (OR = 1.39. 95% CI = 1.15 to 1.68, p = 0.0007). However, being on any antithrombotic therapy is also associated with significantly higher thromboembolic events (OR 5.41, 95% CI 3.16 to 9.26, p < 0.00001). Conclusions: Patients on antithrombotic therapy have both higher recurrence and higher thromboembolic risk compared to patients not on antithrombotic therapy.

Background: Despite efforts to advance equity, women face gender-based barriers in research, including fewer senior authorship and grant opportunities. We examined gender disparities in Canadian Institutes of Health Research (CIHR) funding for Canadian neurology divisions and departments. Methods: Data on CIHR grant recipients and metrics (duration, quantity, and contribution) within Canadian neurology divisions and departments (2008-2022) were acquired from the CIHR Funding Decisions Database. Gender-based differences in grant prevalence, duration, and contribution amount within neurology were calculated with subgroup analysis for Canadian neurologists and Project Grant awards. Results: 1604 grants were awarded to Canadian neurology divisions and departments between 2008-2022. Women received fewer grants (41.46%), less funding (p<0.0001), and shorter grant durations (p<0.0001) than men annually. Women comprised the minority of recipients (45.47%) and were less likely to be awarded grants (p<0.001) annually relative to men. Differences were consistent in subgroup analyses, except grant durations were equal across genders in Project Grant awards. Conclusions: Gender disparities persist in CIHR grant funding to Canadian neurology divisions and departments. Women receive fewer grants, lower contribution amounts, and are less likely to be recipients compared to men. Future work includes addressing gender differences and continuing to evaluate CIHR funding to provide equitable opportunities for women.

Situating itself at the intersection of colonial history, global history and business history, this article highlights the overlooked history of German colonial companies post-First World War. It argues for an ‘imperial afterlife’ through continued German corporate interests in African markets, emphasising the economic dimension of imperialism. Using C. Woermann as an example, it shows how the company adapted to the post-First World War global order, underwent organisational changes, and merged with National Socialist policies in Eastern Europe after 1939, revealing the adaptability of imperial enterprises.

The role of housing in providing a welfare asset has been widely explored. With the growth in home ownership between 1979 and 2008 and erosion of the welfare state, housing wealth has become part of the welfare mix in the UK. Here, we present analysis of housing outcomes, as measured in the UK Household Longitudinal Survey (UKHLS), among people who identify as lesbian, gay, or bisexual in Great Britain. This shows that lesbian, gay, and bisexual (LGB) people have poorer housing outcomes than heterosexual counterparts: they are less likely to be homeowners; more likely to be private renters; and more likely to be social renters. With growing intergenerational inequalities in access to home ownership, we argue that, as openly LGB (and broader trans and queer) people being on average younger than the rest of the population, this could lead to LGB people, as a group, being excluded from asset-based welfare in the future as they age.

Background: Sex and gender are related but distinct determinants of disease, treatment response, and research reproducibility whose consideration is increasingly required for research funding. Nevertheless, the quality of sex and gender reporting in neurological randomized controlled trials (RCTs) remains unknown. Methods: This ongoing study of RCTs associated with Food and Drug Administration neurological drug approvals aims to determine the frequency of accurate reporting of RCT participants’ sex and gender. Secondary outcomes include changes in reporting over time and RCT design characteristics. Results: Preliminary analysis included 145 RCTs (153,410 participants) associated with 77 medications approved in 1985-2023, most commonly for epilepsy (19%), migraine (16%), and multiple sclerosis (16%). Sixty-six RCTs (45.5%) used sex-related terms appropriately. Nine RCTs (6.2%) reported gender accurately. Fifty-three RCTs (37%) used sex- or gender-related terms interchangeably. There are no statistically significant differences in the proportions of studies reporting sex and/or gender accurately when comparing those published until versus after 2017. No RCT reported sex or gender collection methods, definitions of sex or gender, or including sex or gender minority participants. Conclusions: Preliminary results suggest shortcomings in reporting sex and, especially, gender accurately and inclusively among neurological drug RCTs and no significant improvement thereof in recent years.

Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.

Background: Wernicke encephalopathy (WE) is a neurological emergency defined by acute encephalopathy, oculomotor dysfunction, and ataxia. Pediatric cases of WE are underdiagnosed despite having a similar incidence to adults. There are no available treatment guidelines for pediatric WE. Prompt treatment with thiamine can prevent devastating consequences. Methods: A rapid review of the literature of the past 20 years with selected relevant older articles was conducted for the research question “How does child and adolescent thiamine therapy management for Wernicke Encephalopathy compare to adult guidelines?” All articles reporting the investigation, management and treatment of Wernicke encephalopathy – both non alcohol related and alcohol-related pediatric cases – were included. Articles not reporting clinical outcomes were excluded. Results: Eleven case studies including one available review article, met the inclusion and exclusion criteria. An algorithm was created for the organization of published reports of the management of WE for children and adolescents. Key considerations were included for the prevention, identification, acute and ongoing management of patients with WE. Conclusions: The recognition of risk factors for thiamine deficiency and symptoms of acute WE should prompt immediate treatment with thiamine – as a routine and safe therapy in the pediatric population.

Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an investigational gene transfer therapy, developed to address the underlying cause of DMD. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: Ambulatory patients aged ≥4-<8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score >16 and <29 at screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 (n=125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n=63) versus placebo groups (1.9, n=61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4-5 and 6-7 years; p<0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusions: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.

Background: The “weekend effect” is the finding that patients presenting for medical care outside of regular working hours tend to have worse outcomes. There is a paucity of literature in the neuro-oncology space exploring this effect. We investigated the extent of resection and complication rates in patients undergoing after-hours high grade glioma resection. Methods: A retrospective review was conducted on patients with high-grade gliomas requiring emergent surgery between January 2021 to March 2023. After-hours was defined as surgical resection on the weekend and/or evening. These patients were matched to patients undergoing resection during regular working hours. Results: A total of 38 patients were included in this study (19 after-hours, 19 regular hours). There was no significant difference in age, sex, tumor grade, and tumor size between the two groups (all p>0.05). There was no significant difference in the extent of resection between the groups (p=0.7442). There was no significant difference in complications rates, reoperation rates, and death at 6 months (all p>0.05). Estimated blood loss was significantly higher in the regular hours group (p=0.0278). There was no significant difference in the total operative time (p=0.0643) and length of stay (p=0.0601). Conclusions: After-hours high grade glioma surgery is not associated with increased morbidity or mortality.