INTRODUCTION This cross-sectional study explores the diagnostic and management practices of normal pressure hydrocephalus (NPH) in India.METHODS A 16-question online survey based on the Checklist for Reporting Results of Internet E-Surveys checklist was disseminated via closed social media and academic groups.RESULTS A total of 59 neurologists responded. There was significant variability in how the cerebrospinal fluid (CSF) tap test (TT) was implemented. Although 95% of practitioners performed a CSF TT before referring patients for surgery, there were differences in the volume of CSF removed, the assessment tools used, thresholds, and the timing of post-test evaluations. Notably, 36% of neurologists relied on subjective assessment instead of objective scoring to determine CSF TT responsiveness. One-third still considered surgical referral even if the CSF TT was negative, especially when imaging was strongly suggestive of the diagnosis.CONCLUSION This study highlights considerable heterogeneity in the evaluation of NPH in India. We need evidence-based practice parameters to ensure accurate diagnosis, informed treatment decisions, and improved patient outcomes.

Summary: Background: Data of Central Nervous System (CNS) demyelinating disorders from India has been published from limited centres. The Indian Multiple Sclerosis And Allied Demyelinating Disorders Registry and Research Network (IMSRN) is a multicentric database for multiple sclerosis and allied demyelinating disorders in the Indian subcontinent. This study aimed to describe the demographic, clinical, laboratory, treatment, and follow-up details of patients in the IMSRN and summarise the distribution of major disease phenotypes in a real-world cohort. Methods: This was a prospective, observational, registry-based analysis of patients with CNS demyelinating disorders enrolled in the IMSRN between 16 August 2021 and 25 October 2025. Data were collected in a predefined case record form at recruitment and periodically every six months on a secure database. We performed descriptive and comparative analyses, including temporal trends, treatment patterns, and longitudinal follow-up. Findings: As of 25th October, 2025, 4976 patients have been recruited including radiologically isolated syndrome (RIS), 15 (0.30%); clinically isolated syndrome (CIS), 200 (4.02%); multiple sclerosis (MS), 2479 (49.82%); neuromyelitis optica spectrum disorder (NMOSD), 793 (15.94%); myelin oligodendrocyte antibody associated disease (MOGAD), 698 (14.03%); acute disseminated encephalomyelitis (ADEM), 76 (1.53%); chronic relapsing inflammatory optic neuritis (CRION), 34 (0.68%); chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), three (0.06%), and others, 562 (11.29%). The mean (SD) age of the entire cohort at enrolment is 34.62 (12.16) years, at disease onset was 29.12 (11.80) years and median (IQR) disease duration at recruitment is 2.79 (0.51–7.22) years; longest for MS. There were 65.33% females and 34.67% males, with a female-to-male ratio of 1.9:1; highest in NMOSD (3.58:1). Most patients are from urban areas and educated. Optic nerve and spinal cord involvement were the dominant areas at first presentation. The median (IQR) number of relapses per patient over follow-up was 2 (1–3) highest in the NMOSD population; dominated by optic nerve and spinal cord symptoms. The median (IQR) EDSS was 2 (1–4.5). Rituximab was the commonest disease modifying therapy (DMT) used. Longitudinal trends reflect improvement in time-to-diagnosis and significant shift in the pattern of DMT use in MS towards oral DMTs and B-cell inhibitors. Interpretation: The paper describes a cohort of patients with MS and allied disorders. The key disease characteristics of the MS population seem similar to those reported in international MS registries. The data adds to the existing literature to ascertain disease patterns, response to treatment, and long-term outcome. Funding: The IMSRN registry is funded by the Indian Council of Medical Research (ICMR) vide Grant number 5/4-5/192/NeuroTF/2019-NCD-1.

BACKGROUND:Progressive supranuclear palsy (PSP) is a rare and devastating tauopathy with limited global data. Given India's large population, genetic diversity, and clinical heterogeneity, large multicenter datasets are crucial to enrich global understanding of PSP. OBJECTIVE:To characterize the demographic, clinical, and phenotypic profiles of a large multicenter Indian PSP cohort. METHODS:Subjects fulfilling MDS-PSP criteria were prospectively recruited across movement disorders centers (2021-2025). Standardized demographic and clinical data were collected. RESULTS:A total of 1035 subjects were enrolled (M:F = 709:326), with a median age of 65 years and a mean onset age of 62.2 ± 7.9 years. Regional distribution reflected pan-Indian recruitment (South 35%, North 26%, West 21%, East 18%). PSP-Richardson's syndrome was most common (41%), followed by PSP-Parkinsonism (18%) and PSP-CBS (11%); rarer phenotypes included PSP-PI (7%), PSP-F (7%), PSP-PGF (5%), PSP-OM (2%), PSP-SL (1%), and PSP-C (1%). Falls occurred earliest in PSP-PGF (13.7 months) and PSP-SL (16.3 months), while PSP-P showed delayed disability (falls at 31 months) indicating progression patterns. Cognitive onset was prominent in PSP-F (21%) and PSP-SL (57%). Levodopa was prescribed to 893 patients; 186 (21%) reported >25% subjective benefit, and 358 (40%) reported ≤25% benefit. Amantadine was used in 351 (34%) patients, with improvement in 177. CONCLUSION:This largest systematically profiled PSP cohort highlights both shared and distinctive features: high frequency of non-RS variants, aggressive course in PSP-RS/SL, better survival in PSP-P, and limited pharmacological benefit. These findings establish a foundation for longitudinal and genetic studies in diverse populations.

BACKGROUND:In view of paucity of studies, this study compared the effects of local versus intramuscular corticosteroid injections on clinical outcomes and electrophysiological parameters in patients with mild-to-moderate carpal tunnel syndrome (CTS). METHODS:This study enrolled 190 CTS patients between October 2023 to March 2025. Participants were randomized to receive either a single local injection of 40 mg methylprednisolone (MP) with 0.5 mL lidocaine at the wrist (local corticosteroid injection [LCI] arm) or a single 40 mg intramuscular (IM) MP injection in the deltoid (IM arm). The primary outcome was the Symptom Severity Scale (SSS) score at 3 months. Secondary outcomes included SSS at 1 month, Functional Status Scale (FSS), and median nerve electrophysiological changes at 1 and 3 months. Significant clinical response was defined as a reduction of ≥0.8 points in SSS or ≥0.5 in FSS. RESULTS:Follow-up data were missing for 29 patients at 3 months. At 3 months, mean SSS score was 1.51 (SD 0.58) in LCI and 1.64 (SD 0.72) in IM arm (P = .21). However, the LCI arm showed significantly greater reduction in SSS/FSS scores at 1 month. Considering patients lost to follow-up as treatment failures, response rate at 3 months was 70.5% in LCI and 72.6% in IM arm (P = .75). Median nerve conduction results were comparable, although the LCI arm showed greater improvement at 3 months from baseline. CONCLUSIONS:In patients with mild-to-moderate CTS, LCI resulted in greater reduction in Boston Carpal Tunnel Questionnaire scores and in median nerve conductions at 1 month. However, outcome at 3 months was similar.

Parkinson's disease (PD) is a neurodegenerative syndrome with diverse biological drivers, where gait and balance dysfunction remain among the most disabling and least understood symptoms. Bassoon (BSN), a presynaptic active-zone organizer, has been implicated in various parkinsonian disorders. Here, we report the impact of BSN mutations on motor symptoms, especially gait-related symptoms, in PD patients. Our study included 110 patients carrying BSN mutations in a cohort of 668 South Asian early-onset PD (age of onset < 50 years). Clinical motor features were compared between variant carriers and noncarriers. Computational tools (CADD, PolyPhen-2, I-Mutant2.0 and ConSurf) predicted deleteriousness of individual mutations, whereas GeneMANIA and STRING speculated Bassoon's functional interactions. Subjects carrying BSN variants exhibited significantly increased burden of motor-related symptoms (p = 0.036). Freezing of gait (FOG) and shuffling gait (SG) were significantly more prevalent in BSN mutation carriers (p = 0.03). Presence of BSN mutation correlated with an increased disease stage, an effect driven by FOG and SG (p = 0.012). Rare BSN mutations (MAF < 0.1%) clustered in the Bassoon C-terminal region (aa 3500-3800), at a threefold frequency than expected (p < 0.01), implying a hotspot. In silico analysis identified seven likely pathogenic variants (P171L, A852T, P988A, R1015H, R2561H, R3400W and L3561P). Predictive analyses implicated BSN in axonal transport, presynaptic proteostasis and neurotransmitter release in dopaminergic/cholinergic neurons. Our findings put forth BSN mutations as a potential genetic risk factor for PD-related motor and gait dysfunction, warranting further research in this respect.

Background and Aims: Challenges in stroke care exist at multiple levels. In India, medical colleges are crucial in connecting rural and tertiary care public health systems. Our study aims to implement a uniform stroke care pathway (USCP) and assess its sustainability. Methods: IMPETUS Stroke was a multicentric, prospective, multiphase, mixed method, quasi experimental implementation study conducted at 22 government funded medical colleges to examine the changes in a select set of stroke care related indicators over time. It included a pre-implementation phase (Phase-1), followed by an implementation phase (Phase-2) where residents and nursing officers and caregivers were trained and Phase 3, where the sustainability of the USCP was assessed. Results: Patient recruitment in each phase was n=2,018 (19.8%), n=2,179 (21.3%), and n=5,996 (58.8%). Mean age was 59-years and males were higher. Ischemic stroke constituted the largest proportion (60-62%) in all phases. In phase-2, a total of 2103 residents, 2199 nursing officers and 6038 caregivers were trained. Nine of the 22 sites (40%) established their first-ever stroke units. Key stroke care indicators improved from the phase-1 to phase-3: at admission, NCCT (69.6%, 78.1% and 77.0%), CT-angiograms (18.2%, 25.3% and 38.4%), NIHSS (20.3%, 23.7% and 33.1%), thrombolysis rates (39.2%, 65.8% and 70.7%) (p-trend<0.001). The average door-to-CT time significantly decreased (p-trend<0.001), in-hospital stroke management in select indicators improved significantly (p-trend<0.001), in-hospital mortality decreased from 19.4% to 13.5% (p-trend<0.001) and three-months good functional outcome (mRS:0-2) increased from 41.6% to 46.0% (p-trend<0.001) across the phases. Conclusion: The data presented holds significance in showing the effect of implementation in improving stroke services and patient outcomes.

Abstract Parkinson’s disease (PD) arises through disruption of multiple interconnected cellular processes, but the genetic contributions to these processes may differ across ancestries. We investigated functional convergence among genes harboring pathogenic or likely pathogenic (P/LP) variants and variants of uncertain significance (VUS) in a multicenter Indian cohort recruited through the Genetics of Parkinson’s Disease in India–Young-Onset Parkinson’s Disease project (GOPI-YOPD). The cohort included 668 participants (463 males-69.3%) with a mean age at motor onset of 39.4±8.8 years. P/LP variants and VUS identified through previously reported whole-exome or whole-genome sequencing were retained as separate evidential categories. The P/LP-associated gene set comprised 11 unique genes and the VUS-associated set comprised 40 unique genes. Separate STRING functional-enrichment analyses evaluated Gene Ontology Biological Process, Molecular Function and Cellular Component terms, KEGG pathways, WikiPathways and STRING local-network clusters. Terms meeting a Benjamini–Hochberg false-discovery-rate threshold of <0.05 were organized into eight non-mutually-exclusive ontology/pathway categories. Gene-to-pathway mappings were subsequently projected to individual participants to estimate pathway representation and examine clinical associations. At least one reportable P/LP variant or VUS was identified in 336/668 participants (50.3%): 35 had a P/LP variant alone, 282 had VUS alone and 19 had a P/LP variant together with VUS in one or more additional genes. The most frequently represented categories were mitochondrial organization (247/336, 73.5%), autophagy-related processes (228/336, 67.9%) and regulation of synaptic-vesicle transport (201/336, 59.8%). PRKN was the most frequent P/LP-associated gene, occurring in 29/54 P/LP carriers, followed by PLA2G6 and PINK1 . Lysosomal transport was represented exclusively by VUS-associated genes, particularly GBA1 , VPS13C and LRRK2 . Among P/LP carriers, additional VUS in distinct genes were not associated with age at onset (P = 0.81) or family history (52.6% versus 31.4%; P = 0.15). No pathway–phenotype association remained significant after correction for multiple testing. Genetic findings in this Indian cohort converged across an interconnected mitochondrial–autophagic–lysosomal–vesicular network, with different contributions from P/LP-associated and VUS-associated gene sets. This study provides the first pathway-resolved South Asian genetic profile and a framework for comparative studies across populations.

BACKGROUND:The choice of the fourth drug in anti-tubercular therapy for adults with tuberculous meningitis (TBM) remains uncertain. This trial compared the effectiveness and safety of ethambutol (ETM) versus streptomycin (STM) during the intensive phase. METHODS:This is an investigator-initiated, single-center, open-label, randomized controlled trial conducted during October 2020-June 2025. The study was stopped early because of slow recruitment. Patients were randomized to receive either STM (15 mg/kg intramuscular daily; ~90 injections) with isoniazid (H) 5 mg/kg (~300 mg/d), rifampicin (R) 10 mg/kg (~600 mg/d), and pyrazinamide (Z) 25 mg/kg (~1500 mg/d), or ETM (15 mg/kg orally daily) with HRZ for 6 months, followed by RH for 12 months in both arms. Primary outcome was mortality at 6 months. Secondary outcomes included in-hospital mortality and neurologic disability at 3 and 6 months. The disability was assessed using the modified Rankin Scale (mRS) as good (mRS ≤ 2) or poor (mRS > 2). Adverse events were noted. RESULTS:Of 131 patients screened, 49 were excluded. The results therefore are based on 82 patients. The two arms were matched for baseline characteristics. At 6 months, 26 patients had died: 12/42 (28.6%) in the STM arm and 14/40 (35%) in the ETM arm (hazard ratio: 0.78; 95% confidence interval: 0.36-1.70; P = 0.54). In intention-to-treat analysis, there were no differences in in-hospital mortality and disability at 3 and 6 months. Two patients each developed ototoxicity and vision loss in the STM and the ETM arm, respectively. CONCLUSIONS:In adults with TBM, there was no difference in mortality or disability at 6 months between ETM and STM arms, but the study may lack statistical power to detect a difference.The trial was registered in the Clinical Trials Registry of India, CTRI/2020/07/026423 (registered on: 7 July 2020). Key messages What is already known on this topic: The choice of the fourth drug in anti-tubercular therapy (ATT) for adults with tuberculous meningitis (TBM) remains uncertain. Despite extensive use, direct comparisons of ethambutol (ETM) versus streptomycin (STM) in TBM through randomized controlled trials are lacking. What this study adds: In adults with TBM, there was no difference in mortality or disability at 6 months between ETM- or STM-based ATT regimens during the intensive phase. How this study might affect research, practice, or policy: The safety profile of both drugs was comparable; hence, the choice of fourth drug may instead be guided by safety and feasibility.

Background and Objectives: Restless leg syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs, often accompanied by unpleasant sensations such as tingling, crawling, or aching. Symptoms typically worsen during periods of rest or inactivity, particularly in the evening or at night. This scoping review aimed to synthesize the existing literature on the efficacy of cannabis and cannabinoids in alleviating symptoms associated with RLS. Methods: A comprehensive search of electronic databases—including PubMed, Embase, Scopus, Cochrane Library, Google Scholar, ClinicalKey, and ClinicalTrials.gov—was conducted from database inception to April 30, 2025. Various keywords related to cannabis, cannabinoids, and RLS were used to identify relevant clinical studies. Results: A total of 5,370 records were identified, of which seven studies met the inclusion criteria for final review. The evidence suggests that cannabis or cannabidiol may improve or prevent RLS symptoms. Conclusions: Current evidence indicates that cannabis, in various forms, may alleviate or prevent symptoms of RLS through multiple mechanisms. However, the existing literature is limited to case reports, cross-sectional surveys, and post hoc analyses. In the absence of high-quality randomized controlled trials, the evidence is insufficient to support clinical recommendations at this time.

INTRODUCTION:Decompressive craniotomy or craniectomy (DC) is used to treat refractory intracranial hypertension in severe traumatic brain injury and malignant stroke. Heart rate variability (HRV) and blood pressure variability (BPV) may capture autonomic dysfunction and hemodynamic instability in this setting, but their role remains uncertain. This scoping review maps the evidence on HRV, BPV, and related hemodynamic variability in DC patients. METHODS:We conducted a scoping review in accordance with PRISMA-ScR guidelines. MEDLINE, Embase, Cochrane CENTRAL, CINAHL, and Web of Science were searched from inception to June 2025 for studies of any design reporting temporal variability in heart rate or blood pressure in patients undergoing DC. At least two reviewers independently screened records. Findings were summarized descriptively in tables and narrative, stratified by HRV and BPV metrics. RESULTS:Twenty-three studies were included, comprising three randomized controlled trials, one randomized clinical study, and nineteen observational cohorts or case series (five of these were abstracts), with 1765 participants. Most studies enrolled adults with severe traumatic brain injury; a smaller number included malignant middle cerebral artery or other malignant anterior circulation infarction and mixed traumatic and vascular pathologies. Three studies reported formal HRV indices or baroreflex sensitivity, and two studies quantified BPV using statistics such as standard deviation or coefficient of variation; several others evaluated blood pressure instability. HRV was consistently depressed early after DC, and lower time and frequency domain indices were associated with higher mortality and unfavourable long-term neurological outcomes, while higher HRV correlated with better recovery. Higher early postoperative systolic BPV after hemicraniectomy independently predicted worse three-month functional outcomes. Randomized trials showed that ketamine-propofol anesthesia and stepwise decompression reduced intraoperative or early postoperative blood pressure swings without compromising surgical conditions. CONCLUSION:Existing evidence, although limited and heterogeneous, suggests that reduced HRV and increased BPV are associated with worse outcomes in patients undergoing DC. Depressed HRV indices and large BP fluctuations appear to have prognostic value, whereas interventions that stabilize hemodynamics seem to improve early physiological outcomes. Future studies should standardize HRV/BPV measurements, validate these metrics prospectively, and test whether targeting hemodynamic variability can improve neurological outcomes after DC.

Abstract Systemic autoimmune diseases (SAIDs) result from immunological disturbances resulting in multisystem involvement, including the nervous system. These disorders include common diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE) and rare disorders like Behçet’s disease and celiac disease. With the basal ganglia and cerebellum being a common target, movement disorders are reported in several SAIDs. Although the exact pathophysiology is not clear, immune-mediated involvement and inflammatory lesions in the basal ganglia and cerebellum appear to be likely causes for movement disorders in these illnesses. While chorea is the most common movement disorder in SLE and antiphospholipid syndrome, parkinsonism is common in primary Sjögren’s syndrome, and ataxia in neuro-Behçet’s disease and celiac disease. In accordance with the implicated pathophysiology, these disorders often involve immunomodulation, and hence, it is important to suspect and diagnose early.

Neurodegeneration with brain iron accumulation (NBIA) comprises rare genetic neurological disorders typified by pathological iron deposition in basal ganglia. Sleep disturbances remain under-recognized despite involvement of sleep regulating brain areas in NBIA. This multicentre case-control study compares sleep disturbances in genetically-confirmed NBIA patients with age- and gender-matched healthy controls (HC). Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Insomnia Severity Index (ISI), International Restless Legs Syndrome (RLS) study group criteria, Rapid Eye Movement (REM) Sleep Behaviour Disorder Single-Question Screen (RBD1Q), Berlin’s questionnaire were used to assess the risk for poor quality of sleep, excessive daytime sleepiness (EDS), insomnia, RLS, dream-enactment behaviour, and obstructive sleep apnea (OSA), respectively. Four genetically-confirmed NBIA patients (Pantothenase Kinasse-Associated Neurodegeneration = 1, Phospholipase A2-associated neurodegeneration = 2, Mitochondrial membrane protein-associated neurodgeneration = 1) and 24 HCs were included. The median age at presentation was 26.5 years, and median illness duration was 78 months. Dystonia (100

Abstract Prion disorders are rare neurodegenerative disorders resulting from proteinaceous infectious particles and are universally fatal. It can be sporadic, genetic, or acquired. Globally, sporadic Creutzfeldt-Jakob disease is the most commonly reported prion disorder, as well as in India. To delineate the Indian perspective, this study identified and analyzed Indian studies on Prion disorders using the PubMed and Scopus databases. Several Indian case reports and case series suggest a higher prevalence of prion disorders than expected. These disorders commonly affect individuals in the sixth decade of life or later. They are accompanied by rapidly progressive dementia and movement disorders in the form of myoclonus, ataxia, and parkinsonism. The diffusion-weighted sequence of brain magnetic resonance imaging has the highest sensitivity for confirming suspected prion disorders. Short-interval periodic complexes in electroencephalograms are a supportive feature for diagnosing these disorders. Although brain biopsy is the gold standard for their diagnosis, to date, this approach has been performed in <50 Indian cases. Although the results of real-time quaking-induced conversion are comparable to those of histopathological diagnosis, it is not available in India. A pan-India prion disorder registry should be established for the extensive evaluation and systematic collection of data on prion disorders.