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.

Background: Trigeminal neuralgia (TN) is more common in multiple sclerosis (MS) patients than in the general population, likely due to demyelination impacting the trigeminal pathways. While brainstem lesions are associated with MS-TN, their precise role remains unclear. Methods: This study investigates the relationship between brainstem MS plaque location, TN symptoms, and treatment response. We retrospectively analyzed brain MRIs of MS-TN patients, segmenting and coregistering brainstem plaques in MNI space. A tractographic atlas of the trigeminal system was generated using high-resolution diffusion imaging from 30 patients. Lesion involvement was determined by intersection with the trigeminal tract, and its association with pain intensity and treatment outcomes was analyzed using linear regression. Results: Our research revealed 83% of MS-TN patients had brainstem lesions near the fourth ventricle. No single lesion hot spot was identified. Lesion volume did not predict symptom recurrence or treatment response. However, 97% of lesions intersected the trigeminal tract, supporting its association with TN symptoms. Conclusions: The strong overlap between lesions and the trigeminal tract suggests a potential pain generator in MS-TN. Further research is needed to determine whether similar lesions exist in asymptomatic MS patients and to confirm this hypothesis. Future studies will explore whether tract involvement better predicts clinical response to treatment.

Background: Transitioning from home to long-term care (LTC) is challenging for people with dementia and their caregivers. We aimed to elucidate factors predicting long-term care admission within two years of presentation to the Rural and Remote Memory Clinic (RRMC) in Western Canada. Methods: A total of 679 community-dwelling patients were seen at the RRMC in Saskatchewan between its establishment in March 2004 through June 2019. Data analysis included 635 patients (admitted to LTC within two years = 222, not admitted to LTC = 413). Each patient was assessed neuropsychologically and completed self-report questionnaires measuring several domains. Both groups were compared using logistic regression analyses. Results: Univariate logistic regressions showed that age (OR = 1.052, CI = 1.035-1.069), male sex (OR = 1.794, CI = 1.279-2.517), Functional Activities Questionnaire (OR = 1.085, CI = 1.057-1.114), MMSE (OR = 0.861, CI = 0.827-0.897), and Clinical Dementia Rating score (OR = 1.132, CI = 1.062-1.206) remained significant (p < .001). Preserved cognition, as measured by the MMSE, was protective. Conclusions: We found that being older, male, more dependent in activities of daily living, and having increased severity of dementia predicted LTC admission. This information may help in planning care for individuals with dementia.

Background: Self-injurious behaviours (SIB) are repetitive, non-accidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB are prevalent among children with autism spectrum disorder and can lead to permanent disability or death. Neuromodulation at a locus of neural circuitry implicated in SIB, the nucleus accumbens (NAc), may directly influence these behaviours. Methods: We completed a phase I, open-label clinical trial of deep brain stimulation (DBS) of the NAc in children with severe, treatment-refractory SIB (ClinicalTrials.gov NCT03982888). Participants were monitored for 12 months following NAc-DBS to assess the primary outcomes of safety and feasibility. Secondary outcomes included serial assessments of SIB, ambulatory actigraphy, and changes in brain glucose metabolism induced by DBS. Results: Six children underwent NAc-DBS without any serious adverse events. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviours across multiple standardized scales, concurrent with clinically meaningful improvements in quality-of-life. Ambulatory actigraphy showed reductions in high-amplitude limb movements and positron emission tomography revealed treatment-induced reductions in metabolic activity within the thalamus, striatum, and temporoinsular cortex. Conclusions: This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.

Background: Large language models (LLMs) offer potential for clinical decision support but may not fully adhere to current guidelines. Retrieval-augmented generation (RAG) may address this gap by dynamically incorporating external knowledge. This study evaluated LLM adherence with and without RAG to Canadian neuroimaging guidelines. Methods: A novel RAG framework was developed that integrated Canadian Association of Radiologists (CAR) Diagnostic Imaging Referral Guidelines with GPT-4o and o1 models. Clinical scenarios were curated to represent various central nervous system conditions, such as acute stroke, subarachnoid hemorrhage, and multiple sclerosis. Models were prompted with the clinical scenarios, and responses were scored for adherence to the CAR imaging recommendations. Results: Overall, 300 clinical scenarios were used to prompt each model. Adherence rates were 83.8% for GPT-4o, 94.0% for GPT-4o+RAG, 85.5% for o1, and 93.2% for o1+RAG. A Kruskal-Wallis test (H(3)=44.1, p<0.001) identified significant differences among models. Post-hoc comparisons showed RAG-enabled LLMs significantly outperformed standalone models (p<0.001). No significant differences were observed between GPT-4o and o1 without RAG (p=0.531), or between GPT-4o+RAG and o1+RAG (p=0.532). Conclusions: RAG integration significantly improved LLM adherence to Canadian neuroimaging guidelines, even when baseline models demonstrated moderate performance. Future work should validate and explore broader applications of RAG-enabled tools to advance evidence-based care.

Kombucha is a fermented beverage rich in bioactive compounds. This beverage has demonstrated high antioxidant capacity in vitro and experimental animal studies. In this sense, this study aimed to evaluate the effect of daily consumption of green tea kombucha on oxidative stress and endothelial health in individuals with excess body weight. This is a randomized controlled clinical trial, lasting 10 weeks, during which the control group followed a healthy −500 kcal/d energy-restricted diet. In contrast, the kombucha group, in addition to the energy-restricted diet, consumed 200 ml of kombucha green tea daily. This study included men and women aged 18–45 years without chronic diseases. At the beginning and end of the study, fasting blood was collected, and colorimetric assays and immunoassay protocols evaluated markers of oxidative stress and endothelial health. Compared to the control group, kombucha consumption significantly reduced hydrogen peroxide (H2O2) levels (P = 0·007). Initial and final values were as follows: Control group (16·5 v. 15·09 µmol/ml; n 29) and Kombucha group (18·14 v. 14·67 µmol/ml; n 30). The other markers that were evaluated did not change after the kombucha consumption. In conclusion, daily consumption of 200 ml of green tea kombucha for 10 weeks reduces one pro-oxidant marker, without altering other markers of oxidative stress and endothelial health in individuals with excess body weight. Reducing a pro-oxidant marker suggests that kombucha is an antioxidant beverage with promising implications for human health. However, further studies are needed to elucidate other possible beneficial effects on health.

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 the treatment of RTT with the 12-month follow-up of LOTUS. Methods: Caregivers of patients who are prescribed trofinetide under routine clinical care are eligible to participate. Assessments include the Behavioral Improvement Questionnaire (BIQ), the Quality-of-Life Inventory-Disability (QI-Disability) Questionnaire, and the Gastrointestinal Health Questionnaire. Due to ongoing enrollment, data are reported to 9 months since the initiation of trofinetide. Results: In total, 192 patients were included. The median dose reported at week 1 was 45.0% of the target weight-banded label dose; by week 9 onwards, the median dose was at least 80.0% of the target weight-banded label dose. Behavioral improvements reported with the BIQ were nonverbal communication (49–62%), alertness (43–62%), and social interaction/connectedness (32–52%). The QI-Disability Questionnaire median total scores indicated overall improvement in quality of life (QoL) with trofinetide. Caregivers reported that patients were most likely to void normal stools over the follow-up; most reports of diarrhea were contained inside the patient’s diaper. Conclusions: Caregivers of patients with RTT in LOTUS reported behavioral improvements of RTT symptoms and improvement in patients’ QoL.

Background: Stroke is a leading cause of disability worldwide, resulting in long-term impairments requiring rehabilitation. Frailty, characterized by reduced physiological reserve and vulnerability to stressors, is associated with poor health outcomes. When assessed using the Clinical Frailty Scale (CFS), frailty has been linked to adverse outcomes; however, its role in stroke rehabilitation remains underexplored. This study investigates the impact of pre-stroke frailty on functional recovery during inpatient stroke rehabilitation. Methods: A retrospective cohort study was conducted on 206 stroke patients admitted between 2020-2022. Pre-stroke frailty was assessed using the CFS, and rehabilitation outcomes were measured using Functional Independence Measure (FIM) gain and efficiency. Differences across CFS categories, stroke location, age, and sex were statistically analyzed. Results: Among these patients, 42.7% were female, and 75.7% were aged 60 or above. There were no significant differences in FIM gain or efficiency across CFS categories (p > 0.05). Frailty was associated with lower admission (p = 0.041) and discharge (p = 0.032) FIM scores. Conclusions: Pre-stroke frailty, assessed retrospectively using the CFS, does not predict functional improvement or efficiency during inpatient rehabilitation. However, frailty was associated with poorer functional status at admission and discharge. All patients meeting the admission criteria benefited from rehabilitation, regardless of frailty level.

Background: This scoping review investigates factors influencing local control in patients with metastatic brain disease undergoing adjuvant stereotactic radiosurgery (SRS) to surgical cavities. Methods: Seven databases (Ovid Medline, PubMed, Web of Science, EMBASE, BIOSIS, Scopus, Global Health, Cochrane) were searched up to August 2, 2021, using terms related to radiosurgery and brain metastasis. A three-level screening identified relevant studies. Data extraction included study type, population, SRS details, and outcomes. Variables recorded were histopathology, resection degree, number of metastases, SRS platform, dose parameters, cavity volume, margin, time to SRS, local control at 12/24 months, overall, and progression-free survival. Significant predictors were noted. Results: From 10,633 articles, 22 studies with 1,749 cavities. Local control at 12 months was 50–100% (median 82%, IQR 73–84.4%). Distant progression at 12 months was 36–64% (median 45.5%, IQR 38–51%) and at 24 months 39–76% (median 53%, IQR 46–55%). Histology, radiation dose, tumor size, extent of resection, treatment timing, tumor depth, and dural/pial attachment impacted local control, whereas primary disease status, surgical corridor coverage, and tumor location did not. Conclusions: Modifiable SRS treatment and patient selection factors need further investigation. This review emphasizes the necessity for consensus and guides future trials and guidelines to enhance metastatic brain disease management outcomes.

Background: Ischemic stroke often results in long-term motor impairments due to disrupted corticospinal pathways. Transcranial magnetic stimulation (TMS) motor mapping is a non-invasive technique used to assess corticospinal integrity by measuring motor evoked potentials (MEPs). This study investigates whether MEP amplitudes can predict impairment severity and functional performance in chronic stroke. Methods: Four non-human primates (NHPs) with chronic stroke (> six months) following transient right middle cerebral artery occlusion underwent TMS motor mapping using neuronavigation under ketamine anesthesia. Single pulses of TMS (50-70% of maximum stimulator output) were applied to the affected and contralesional primary motor cortices to elicit MEPs and assess cortical excitability. Intramuscular electromyography recorded muscle responses from the biceps, extensor digitorum longus, and abductor pollicis brevis. Neurological dysfunction was evaluated daily for three weeks using the NHP Stroke Scale, NHP Upper Extremity Motor Dysfunction Scale, and the primate Rankin Scale. Results: MEPs were present in NHP1, NHP3, and NHP4 but absent in NHP2. Stronger MEPs correlated with lower impairment severity and better functional performance, while NHP2 exhibited higher impairment and poorer performance. Conclusions: MEP presence and strength can serve as biomarkers of motor recovery potential, highlighting their role in assessing corticospinal integrity and functional outcomes.

Background: Neck vessel imaging is often performed in hyperacute stroke to allow neurointerventionalists to estimate access complexity. This study aimed to assess clinician agreement on catheterization strategies based on imaging in these scenarios. Methods: An electronic portfolio of 60 patients with acute ischemic stroke was sent to 53 clinicians. Respondents were asked: (1) the difficulty of catheterization through femoral access with a regular Vertebral catheter, (2) whether to use a Simmons or reverse-curve catheter initially, and (3) whether to consider an alternative access site. Agreement was assessed using Fleiss’ Kappa statistics. Results: Twenty-two respondents (7 neurologists, 15 neuroradiologists) completed the survey. Overall there was slight interrater agreement (κ=0.17, 95% CI: 0.10–0.25). Clinicians with >50 cases annually had better agreement (κ=0.22) for all questions than those with fewer cases (κ=0.07). Agreement did not significantly differ by imaging modality: CTA (κ=0.18) and MRA (κ=0.14). In 40/59 cases (67.80%), at least 25% of clinicians disagreed on whether to use a Simmons or reverse-curve catheter initially. Conclusions: Agreement on catheterization strategies remains fair at best. Our results suggest that visual assessment of pre-procedural vessels imaging is not reliable for the estimation of endovascular access complexity.