Background: Eccrine carcinoma is a rare skin tumor arising in eccrine sweat glands with a predilection for older adults. Over 30% of cases occur in the head and neck. Local and distal metastases are common. Prognosis is poor with regional recurrence in up to 19% of cases. Imaging is indicated in high-risk disease. Methods: We present a case report of eccrine carcinoma in the scalp with perineural metastasis to the left trigeminal nerve. Results: A seventy-nine-year-old male with a history of left temporal scalp pre-cancerous lesion treated with liquid nitrogen two years prior presented with left facial pain and paresthesia. The gadolinium-enhanced MRI head showed a tiny sub-centimetre spiculated subcutaneous lesion in the left temporal scalp and perineural enhancement along the left auricotemporal, V3 and trigeminal nerves. Subsequent excisional biopsy of the temporal lesion showed a poorly differentiated eccrine carcinoma without local perineural invasion. Conclusions: Undifferentiated facial pain is a frequent indication for head imaging, usually with low diagnostic utility. However, scrutiny for perineural enhancement is necessary to avoid missing a potentially deadly process. Eccrine carcinoma is a rare type of skin cancer. Small, painless, indolent primary lesions may be overlooked clinically. Radiologists can affect outcomes in these cases.

Background: COMISA (comorbid insomnia and obstructive sleep apnea) is associated with daytime functioning and cognitive impairments. This post hoc analysis assessed the impact of lemborexant (LEM), a dual-orexin-receptor-antagonist approved to treat insomnia in adults, on morning sleepiness/alertness in participants with COMISA. Methods: Of the overall population (n=1006), 410 (40.8%) adults (≥55 years) with comorbid insomnia disorder and mild obstructive sleep apnea (apnea-hypopnea-index, 5–≤15 events/h) from Study E2006-G000-304 (NCT02783729), a 1-month, randomized, placebo- and active-controlled study, were analyzed. Participants received placebo (PBO), LEM 5mg (LEM5), LEM 10mg (LEM10), or zolpidem tartrate 6.25mg (not reported). A daily sleep diary assessed morning sleepiness/alertness (1, extremely sleepy to 9, extremely alert). Participants (%) shifting from baseline mild/moderate sleepiness (≤3) towards greater alertness (4, 5, or >5) during the first/last 7 mornings of the study were analyzed. Results: At baseline, 17/75 (22.7%), 36/112 (32.1%), and 28/104 (26.9%) participants with COMISA receiving PBO, LEM5, or LEM10, respectively, reported mild/moderate sleepiness. Across the first/last 7 mornings, more participants shifted from mild/moderate sleepiness towards alertness with LEM5 (66.7%, 82.9%) and LEM10 (64.3%, 75.0%) versus PBO (47.1%, 64.7%), respectively. Conclusions: A greater percentage of participants with COMISA experienced improvements in morning sleepiness across the treatment period with LEM versus PBO.

Background: Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) are associated with pathogenic variants in SCN1A. While most such cases are heterozygous, there have been 16 reported homozygous cases. We report two new biallelic cases associated with divergent phenotypes.Methods: We performed a chart review for two patients with different homozygous SCN1A variants and reviewed all previously published biallelic SCN1A pathogenic variants. Results: Our first patient exhibited early afebrile seizures and severe developmental delay, without febrile seizures or status epilepticus. A homozygous c. 1676T>A, (p. Ile559Asn) variant of uncertain significance was identified, carried by asymptomatic parents. The second patient exhibited early, recurrent, and prolonged febrile seizures, moderate developmental delay, and motor dysfunction; a homozygous pathogenic c. 4970G>A, (p. Arg1657His) variant carried by asymptomatic parents was identified.

Of 18 known cases of biallelic SCN1A pathogenic variants, 15/18 (83%) have diagnoses of Dravet or GEFS+. The remaining 3/18 (17%) had pharmacoresponsive epilepsy with prominent GDD. Cognitive phenotypes ranged from intact neurodevelopment to profound developmental delay. Eleven out of 18 cases (61%) had motor concerns. Conclusions: These cases expand the phenotypic spectrum of biallelic SCN1A variants. While some patients present typically for Dravet/GEFS+, others present with developmental delay and controllable epilepsy.

Background: Subdural hematoma (SDH) is a serious complication of shunt surgery for normal pressure hydrocephalus (NPH). Since the introduction of adjustable valves, management strategy has changed significantly. Methods: A retrospective review of NPH patients treated in the Hydrocephalus and CSF Disorders Clinic over the past five years was conducted. A review of clinical materials and imaging identified 32 patients who developed SDH following shunt surgery for NPH. Results: Twenty-seven patients were male and five were female. Mean age was 74. All patients received programmable valves. Nineteen patients were diagnosed with SDH within six months of shunt insertion, with a mean duration to diagnosis of 48 days. Five required surgery. The remaining 14 patients were treated successfully with shunt adjustment. All patients returned to their clinical baseline. Thirteen of the 32 patients developed SDH after a period of six months, with a mean duration to diagnosis of 43 months. None required surgical intervention. Ten patients were treated with shunt adjustment. The remainder were observed. Conclusions: Close surveillance following shunt insertion, particularly within the first six months post-op, is essential to prevent significant clinical sequelae secondary to SDH. Programmable valves can play an important role in early SDH management.

Background: Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder, characterized by gradual loss of motor, verbal and social skills. This study describes the epidemiology and healthcare resource utilization (HCRU) of RTT in Ontario, Canada. Methods: RTT patients (≥ one ICD-10-CA code F84.2) were identified using data held at the Institute for Clinical Evaluative Sciences (ICES), between September 2018-August 2023. Incidence and prevalence rates from Ontario were extrapolated nationally using the Stats Can population estimates. Results: A total of 246 patients were indexed; 95% female, median age 21 years and 40% from central Ontario. There were 57 incident and 257 prevalent RTT cases identified in Ontario. National extrapolations estimated 175 incident and 613 prevalent RTT cases. Common comorbidities included developmental disability (85.4%) and epilepsy (49.6%). Patients frequently had outpatient visits (primary care 96.7%, specialists 86.6%), emergency department visits (76.8%) and inpatient hospitalizations (54.5%). Most patients (95.1%) had at least one public claim for all-cause medication. Disease-specific medication claims were for anti-infectives (69.1%) and anti-seizure medications associated with mood effects (65.0%). Conclusions: This study provides population-based estimates of RTT in Canada. Findings highlight the high burden of illness and HCRU of RTT and the opportunities to improve healthcare outcomes in this population.

Background: Trofinetide is approved for the treatment of Rett syndrome (RTT) in patients aged ≥2 years. Here, we present the benefits and tolerability of trofinetide in pediatric and adult patients with RTT from the LOTUS study. Methods: Caregivers of patients who are prescribed trofinetide under routine clinical care are eligible to participate. This subgroup analysis of the 12-month follow-up of LOTUS focused on pediatric (0–17 years of age) and adult (≥18 years of age) patient populations. Due to ongoing enrollment, data are reported to 9 months since the initiation of trofinetide. Results: In total, 117 pediatric and 74 adult patients were included. The median dose reported at week 1 was 45.0% and 41.0% of the target weight-banded label dose for pediatric and adult patients, respectively; by week 8, the median dose was at least 86.0% and 70.0% of target, respectively. Behavioral improvements included nonverbal communication (pediatric: 53–64%; adult: 41–58%), alertness (pediatric: 50–69%; adult: 33–65%), and social interaction/connectedness (pediatric: 36–58%; adult: 26–46%). Most reports of diarrhea were contained inside the patients’ diapers. Conclusions: Caregivers of pediatric and adult patients with RTT in LOTUS reported improvements consistent with the general population of the study.

Background: Glioma trials may use selective criteria, limiting their generalizability to real-world patients. This systematic review and meta-analysis quantifies the prevalence of these criteria and evaluates their impact on trial outcomes, assessing whether reducing selectivity to improve generalizability and applicability is feasible without compromising safety or efficacy. Methods: 51 glioma trials were extracted from the National Clinical Trial (NCT) database on June 1st, 2024. Eligibility criteria were classified as selective—defined as likely to exclude patients who could benefit, or generalizable—justified due to potential harm or trial focus. The selective criteria were analyzed for correlation with median overall survival (mOS). Results: The average number of selective criteria per study was 6.8 (range: 0–14, median: 7). The most common were “No prior malignancy with a specified disease-free period” (N=29), “Exclusion based on Karnofsky score” (N=27), and “No prior brain radiotherapy” (N=16). Meta-analysis showed no significant correlation between the number of selective criteria and mOS (p = .327). Conclusions: Selective criteria are common in glioma trials, particularly exclusions based on prior malignancies, performance status, and past treatments. However, their lack of correlation with mOS indicates minimal impact on outcomes. These findings suggest reducing selectivity in trial criteria may improve generalizability and applicability without compromising safety or efficacy.

Background: In multiple sclerosis (MS), soluble mediators of neuroinflammation are released by activated lymphocytes and resident immune cells, leading to demyelination and neurodegeneration. Radiologically isolated syndrome (RIS) is an entity in which white matter lesions fulfilling criteria for MS occur in individuals without any suggestive symptoms. The exact nature of pro- and anti-inflammatory cytokines in blood, and their association with disease activity in RIS/MS requires further clarification. Methods: Plasma was collected and cryopreserved from healthy controls (HCs), people with RIS and relapsing-remitting MS (RRMS) at the Barlo MS Centre. All samples were analyzed with OLink Target 96 Inflammation Multiplex Immunoassay Panel. Results: Individuals with RIS (p=0.0001; p= 0.0007; p= 0.0012) and RRMS (p<0.0001; p= 0.0003; p= 0.00112) had significantly higher concentrations of hepatocyte growth factor (HGF), interleukin-6 (IL-6), and chemokine ligand 23 (CCL23) in plasma compared to HCs, and patients with RRMS (p=0.0087) had significantly higher concentrations of HGF compared to individuals with RIS. Conclusions: Our study demonstrates that HGF, IL-6 and CCL23 are significantly increased in the plasma of patients with RIS and RRMS compared to HCs. Our observations suggest that the biology of MS is present in those with RIS, and these neuroinflammatory mediators may serve as a biomarker of disease activity.

Background: Status dystonicus is characterized by frequent or prolonged severe episodes of generalized dystonia. The phenomenology, etiology, and outcome is heterogenous and poorly characterized, making a standardized management approach challenging. We characterized demographics of children with status dystonicus in British Columbia admitted to the pediatric intensive care unit (PICU), management patterns, and outcomes. Methods: Clinical records at our PICU were searched via ICD-10 codes. We included cases admitted 2014-2024 who had dystonia severity grade 3-5, dystonia worse than baseline, and age >30 days old. Results: Seventy-nine records were screened; 41 admissions from 19 unique patients were included. Mean age was 7.6±4.2 years; 53% were female. Most unique patients had a genetic etiology (n=8, 42%). The presenting complaint per admission was often not dystonia (n=24, 59%); infection was the most common trigger (n=23, 56%) followed by pain (n=6, 15%). Patients received several anti-dystonia medications (mean 6.9±2.5), including clonidine, benzodiazepines, ketamine, and others. Mean PICU stay was 11.0±10.8 days; 37% had multiple PICU admissions. Two patients (4.9%) died from status dystonicus complications. Conclusions: Status dystonicus is a life-threatening emergency commonly triggered by pain and infection in patients with dystonia. Given the considerable morbidity and mortality, multi-disciplinary teams should consider standardized treatment guidelines for these complex patients.

This article studies the aftermath of the Second World and decolonization (1945–1960) in the Indo-Burmese highlands, challenging predominant notions of state-building. Using the ‘Zomia’ heuristic, it argues how trans-border Naga tribal communities residing in so-called ‘No-Man’s-Lands’ between British India’s Assam province and Burma neither entirely resisted states, nor attracted uniform state interest. This dual refusal of states and social actors reveals negotiated sovereignty practices, using violence. The article illustrates the Naga tribes’ agency in negotiating with colonial and post-colonial states by using mimetic discourses of primitive violence, represented by headhunting. Violence served as a significant means of communication between communities and state agents, amounting to shifting cultural and territorial boundaries. Such practices selectively securitized colonial frontiers that became international borders post-decolonization. Gradually, violence and the desire for development invited state extension here. The article reveals that uneven state-building and developmental exclusions by bordering created conditions for violence to emerge. It engages scholarship on ‘Blank Spaces’ to analyse the varying sovereignty arrangements that produced ‘checkered’ zones. It highlights the relationship between spatial history and violence to explain the persistence of coercive development and demands for more borders and states today across highland Asia. It uncovers the embeddedness of violence in creating and challenging developmental and democratic exclusions in post-colonial nation-building projects. The analysis complicates imperial legacies of producing territorial enclosures within democracies, allowing exceptional violence to occur. More broadly, it complicates contemporary geopolitical cartographic contests and stakes of state-possession, using historical methods with approaches from anthropology and political geography.

Background: Analysis of 20 pairs is the traditional standard when using SFEMG to diagnose MG. Some studies show that fewer pairs are needed if results are normal. We examined what impact this might have on long-term outcomes. Methods: Hospital charts of 239 consecutive patients who underwent SFEMG between January 2011, and July 18th, 2024, were reviewed. Results: 201 patients were identified; 128 had normal SFEMGs. Of the patients with normal SFEMGs, 58 (45.31%) had 12 pairs observed and 69 (53.91%) had 20 or more pairs observed. In the 12 pair group, 1(1.72%) patient had delayed MG diagnosis, and 2 (3.45%) patients were referred for repeat SFEMGs; in the 20 or more group, 2 (2.90%) patients belong in each aforementioned category. No patients from either group were hospitalized for MG after SFMEG. Conclusions: Preliminary results demonstrate no difference in frequency of poor outcomes between patients who had 20 or more pairs observed and those who had 12 pairs observed, supporting the safety of shortening the test in appropriate situations.

Background: Epilepsy affects approximately 3% of Canadian children. Despite the availability of standardized seizure abortion guidelines, many patients require personalized treatment plans due to genetic factors, medical contraindications, or a history of adverse medication reactions. This study aims to create and evaluate personalized Acute Seizure Action Plans (ASAPs) for epilepsy patients at the Children’s Hospital of Eastern Ontario (CHEO). Methods: Using a Plan-Do-Check-Act (PDCA) framework, we developed electronic ASAPs for integration into participants’ electronic medical records. The effectiveness and user satisfaction of these ASAPs will be evaluated through electronic surveys administered to Neurology physicians, Emergency Department (ED) physicians, and patient participants at baseline and six months post-implementation. Results: Baseline surveys were administered to ED physicians with a 70% response rate, indicating only 43% satisfaction with current generic seizure treatment practice. One hundred percent of respondents expressed interest in using an ASAP, citing challenges in selecting the appropriate anti-seizure medications and determining when to adjust treatment as priorities. These findings underscore the need for ASAP implementation. Conclusions: ED providers desire improved seizure action plans. ASAP implementation is expected to enhance emergency seizure management, reduce adverse events among epilepsy patients, and increase satisfaction of seizure management among all participants.

Background: Ketogenic diet can be an effective alternative therapy for medication refractory infantile spasms. Infantile spasms are more prevalent in children with Down syndrome compared with the general population and often medication refractory. Methods: Charts of infants who presented to the Children’s Hospital of Eastern Ontario with Down syndrome and refractory infantile spams treated with ketogenic diet from 2012 to 2025 were reviewed. Clinical response defined by cessation of epileptic spasms and resolution of hypsarrhythmia. Diet ratio,tolerance, side effects, concomitant medications, and diagnostic tests were evaluated. Results: 5 infants were treated with ketogenic diet after failing first line anticonvulsant mendications: viagabatrin and corticosteriods. Ketogenic diet was viable only via G-tube in 1 patient and by NG tube in 3 due to risk of aspiration. Diet was compatible with second line anticonvulsants. Complete electroclinical response occurred in 2 infants after 4 weeks. Partial seizure reduction and electrographic improvement was observed in 1 infant. 1 patient died due to unrelated respiratory illness. Conclusions: Ketogenic diet is a viable potentially effective therapeutic option for infants with Down syndrome and medication refractory infantile spasms. These infants present challenges inherent of Down syndrome such as hypotonia, higher risk for aspiration which need to be considered before diet introduction.

Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.

Background: Nipocalimab is a human IgG1 monoclonal antibody targeting FcRn that selectively reduces IgG levels without impacting antigen presentation, T- and B-cell functions. This study describes the effect of nipocalimab on vaccine response. Methods: Open-label, parallel, interventional study randomized participants 1:1 to receive intravenous 30mg/kg nipocalimab at Week0 and 15mg/kg at Week2 and Week4 (active) or no drug (control). On Day 3, participants received Tdap and PPSV®23 vaccinations and were followed through Wk16. Results: Twenty-nine participants completed the study and are included (active, n=15; control, n=14). Participants with a positive anti-tetanus IgG response was comparable between groups at Wk2 and Wk16, but lower at Wk4 (nipocalimab 3/15 [20%] vs control 7/14 [50%]; P=0.089). All maintained anti-tetanus IgG above the protective threshold (0.16IU/mL) through Wk16. While anti-pneumococcal-capsular-polysaccharide (PCP) IgG levels were lower during nipocalimab treatment, the percent increase from baseline at Wk2 and Wk16 was comparable between groups. Post-vaccination, anti-PCP IgG remained above 50mg/L and showed a 2-fold increase from baseline throughout the study in both groups. Nipocalimab co-administration with vaccines was safe and well-tolerated. Conclusions: These findings suggest that nipocalimab does not impact the development of an adequate IgG response to T-cell–dependent/independent vaccines and that nipocalimab-treated patients can follow recommended vaccination schedules.

Background: Treatment-resistant obsessive compulsive disorder (trOCD) is a condition characterized by intrusive thoughts (obsessions) and uncontrollable behaviours (compulsions) unresponsive to conventional therapies. Lesioning both anterior limbs of the internal capsule is effective in ablating the circuitry underlying trOCD pathophysiology. The newest capsulotomy method is MR-guided focused ultrasound (MRgFUS). Here we measured neural networks changes of trOCD patients after MRgFUS capsulotomy using resting state functional MRI (rs-fMRI). Methods: Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and rs-fMRI data were collected in 6 trOCD patients preoperatively, postoperatively at 3-months and 1-year, along with rs-fMRI from 6 age and sex-matched controls. Independent component analysis, dual regression using the FMRIB software library, and node-node approaches were used with the CONN Toolbox. We also performed a systematic review of existing studies about trOCD resting state networks. Results: TrOCD patients demonstrated significant improvement 1-year postoperatively (mean YBOCS reduction of 41 ± 7%). Dual regression analysis 3-months postoperatively showed significantly greater sensorimotor network signal in controls compared to trOCD groups. Node-node analysis in trOCD found connectivity changed in networks associated with the cortico-striato-thalamo-cortico loop, particularly the salience and limbic networks at 1-year postoperatively. Conclusions: TrOCD patients who underwent MRgFUS capsulotomy demonstrated differences in sensorimotor and cortico-striatal connectivity and significant clinical improvement postoperatively.

Background: Identifying the pituitary gland during surgery for pituitary neuroendocrine tumors (PitNET) is crucial for preserving gland tissue and reducing postoperative hormonal dysfunction. This study aimed to develop and validate a machine learning (ML) tool to identify the pituitary gland during endoscopic endonasal surgery. Methods: Anonymized surgical videos from PitNET resections were trimmed to key phases, starting after dura opening and ending before skull base reconstruction. Frames were manually annotated to delineate the pituitary gland’s location. The ML model’s performance was evaluated using a single hold-out set method. Results: A total of 2316 frames from 52 videos were annotated, with 60%, 20%, and 20% allocated to training, validating, and testing the ML model, respectively. Performance metrics were as follows: accuracy of 97.8%, specificity of 98.7%, recall of 27%, precision of 18.6%, and an F1-score of 0.22. Conclusions: This study highlights the feasibility of using ML to identify the pituitary gland in PitNET surgeries. While the model is highly accurate in distinguishing gland from non-gland tissue, its low precision indicates a propensity to misclassify adjacent background tissue as pituitary gland.Further refinements could enhance its precision, making it a valuable tool for improving intraoperative anatomical recognition and postoperative hormonal outcomes.