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A quantitative disorder-phenotype atlas of inherited metabolic disorders reveals shared symptom spaces and group-specific hotspots

PubMed - neurological misdiagnosis Published 14 Oct 2026 Relevancy: 49%

CONCLUSIONS: This first-generation knowledgebase-level atlas quantifies reported disorder-level phenotype architecture rather than patient-level prevalence or natural history. It provides a scalable framework for phenotype standardization, diagnostic navigation, targeted curation, and future integration of age, variants, treatment, and real-world evidence.

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Functional outcome after ischaemic stroke and intracerebral haemorrhage from two national cohorts

Journal of Neurology, Neurosurgery & Psychiatry - Online First Published 13 Oct 2026 Relevancy: 42%

WHAT IS ALREADY KNOWN ON THIS TOPIC It is widely assumed that outcome is worse after intracerebral haemorrhage (ICH) compared with acute ischaemic stroke (AIS), but there is a lack of contemporary data to confirm or refute this assumption or explain any differences. WHAT THIS STUDY ADDS In this large observational study pooling individual data of 111 038 patients from two national stroke registries from high-income countries with universal healthcare access, ICH was associated with poorer outcome at 3 months compared with AIS (adjusted OR for favourable functional outcome: 0.42, 95% CI 0.39 to 0.45, p<0.001). The association was only partly mediated by higher baseline stroke severity and the availability of recanalisation therapies for AIS. Half of the effect remains unexplained by measures of stroke severity and is potentially attributable to overall care limitations in patients with ICH. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY This study highlights key differences in outcomes...

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Cerebrospinal fluid haemoglobin as a monitoring biomarker for secondary brain injury after aneurysmal subarachnoid haemorrhage: prospective international multicentre validation study (HeMoVal)

JNNP - Current Issue Published 13 Oct 2026 Relevancy: 43%

WHAT IS ALREADY KNOWN ON THIS TOPIC Preclinical animal models link cell-free haemoglobin in cerebrospinal fluid (CSF-Hb) to secondary brain injury after aneurysmal subarachnoid haemorrhage (SAH-SBI). A single-centre study reported strong associations between daily external ventricular drain (EVD)-derived CSF-Hb levels and SAH-SBI, and suggested a strong predictive potential (area under the curve 0.89). CSF-Hb monitoring has therefore been proposed as a bedside biomarker, but it has not undergone multicentre validation. WHAT THIS STUDY ADDS In a preregistered multicentre cohort of 366 patients from eight neurosurgical centres, once-daily EVD-derived CSF-Hb measurements showed poor same-day discrimination for SAH-SBI (area under the curve 0.59) and substantial between-centre heterogeneity. In a post-hoc exploratory analysis, higher CSF methaemoglobin was associated with SAH-SBI; higher acute-phase CSF-Hb was related to chronic hydrocephalus and a worse 3 month functional outcome. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY These...

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Durable fluoropolymer drug-eluting stent versus bare-metal stent for the prevention of intracranial in-stent restenosis

JNNP - Current Issue Published 13 Oct 2026 Relevancy: 15%

WHAT IS ALREADY KNOWN ON THIS TOPIC Although drug-eluting stents (DES) reduce the risk of in-stent restenosis (ISR) compared with bare-metal stents (BMS) in symptomatic intracranial atherosclerotic stenosis (ICAS), the reported 1-year ISR rate (9.5%) of current intracranial DES remains higher than that reported in coronary practice (2.5%–4.9%). WHAT THIS STUDY ADDS In this multicentre randomised trial of 156 patients with symptomatic ICAS, durable fluoropolymer DES significantly reduced the 1-year ISR rate to 2.9% versus 27.9% with BMS, achieving the lowest ISR rate reported in an intracranial DES randomised trial to date. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY Durable fluoropolymer DES may be a promising device option for reducing ISR and providing a rationale for future randomised controlled trials comparing endovascular treatment with aggressive medical management in high-risk ICAS. Introduction Intracranial atherosclerotic stenosis (ICAS) is a leading...

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Age and treatment class modify inflammatory risk after disease-modifying therapy discontinuation in older people with MS

JNNP - Current Issue Published 13 Oct 2026 Relevancy: 53%

WHAT IS ALREADY KNOWN ON THIS TOPIC Discontinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS) can be followed by inflammatory reactivation, even in older patients, but the age threshold at which this risk becomes substantially attenuated remains unclear. WHAT THIS STUDY ADDS In this propensity score-matched, prospective cohort of people with MS aged ≥50 years, inflammatory outcomes after DMT discontinuation vary by age and treatment mechanism, with attenuation of risk in individuals aged >60 years and among those discontinuing anti-CD20 therapies. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY Age and treatment mechanism may help inform individualised risk stratification when considering DMT discontinuation in older people with MS. Introduction The proportion of older people with multiple sclerosis (MS) is steadily increasing,1 likely due to better prognosis,2 advances in disease-modifying therapies (DMTs) and expanded access...

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Comparative effectiveness of ofatumumab and ocrelizumab in relapsing multiple sclerosis: a target trial emulation using multinational registry data

JNNP - Current Issue Published 13 Oct 2026 Relevancy: 46%

WHAT IS ALREADY KNOWN ON THIS TOPIC Ofatumumab and ocrelizumab are widely used high-efficacy anti-CD20 therapies for relapsing multiple sclerosis, but direct comparative evidence is limited. Prior observational studies have generally reported similar effectiveness between the two treatments, with low relapse rates and no clear differences in disability outcomes. WHAT THIS STUDY ADDS In this large real-world cohort, both therapies showed high effectiveness, but small differences were observed: ocrelizumab was associated with lower relapse rates, whereas ofatumumab was associated with a lower risk of disability progression. Absolute differences were significant but very small. Findings were consistent across sensitivity analyses. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY Our findings highlight the clinical equivalence of ocrelizumab and ofatumumab. However, the small but significant divergence between relapse and disability outcomes between these drugs could be due to differences in administration frequency or drug availability,...

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HLA-dependent association between EBNA1 antibody levels and disability progression in multiple sclerosis

JNNP - Current Issue Published 13 Oct 2026 Relevancy: 56%

WHAT IS ALREADY KNOWN ON THIS TOPIC Epstein-Barr virus (EBV) is strongly implicated in multiple sclerosis (MS) susceptibility, but the relevance of EBV-related immune responses for disability progression after disease onset remains unclear. Previous studies of EBV antibodies and MS course have shown inconsistent findings and have rarely considered modification by HLA genotype. WHAT THIS STUDY ADDS In this population-based cohort study, higher EBNA1 antibody levels were associated with a lower risk of disability progression, with the strongest inverse association observed among individuals carrying both HLA-DRB1*15:01 and HLA-A *02:01. The findings suggest that the association between EBV-related antibody responses and MS progression may vary according to host immunogenetic background. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY The results support more genetically stratified approaches in studies of biomarkers and disease progression in MS and suggest that EBV-related immune markers should not be...

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Global epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis

JNNP - Current Issue Published 13 Oct 2026 Relevancy: 60%

WHAT IS ALREADY KNOWN ON THIS TOPIC Global systematic reviews of amyotrophic lateral sclerosis (ALS) epidemiology exist, but evolving demographic patterns and updated diagnostic criteria necessitate updated disease burden estimates. WHAT THIS STUDY ADDS This study provides updated pooled global estimates of ALS incidence, prevalence and mortality and confirms substantial heterogeneity in ALS disease burden across demographic, temporal, geographical and socioeconomic dimensions. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY These findings highlight multifaceted disease disparities attributable to genetic, environmental and socioeconomic factors, supporting healthcare policy making, optimised resource allocation and ongoing ALS research. Introduction Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by progressive muscle weakness and atrophy, resulting from the degeneration of motor neurons in the cerebral cortex, brainstem and spinal cord.1 2 ALS is the most prevalent motor neuron disease...

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Associations of self-reported and objectively measured physical activity and amyotrophic lateral sclerosis risk

JNNP - Current Issue Published 13 Oct 2026 Relevancy: 35%

WHAT IS ALREADY KNOWN ON THIS TOPIC Multiple studies have linked strenuous exercise to higher ALS risk in highly selected populations, such as specific athlete groups, but several population-based studies failed to find a positive association between physical activity and ALS risk, and some have even found an inverse association. Moreover, although intervention to prevent ALS is most feasible in carriers of ALS-associated genetic variants, only one study investigated the effect of physical activity on ALS risk in this group, using retrospective analysis in 17 C9ORF72 expansion carriers. WHAT THIS STUDY ADDS This study incorporates data from a large population-based prospective cohort of 384 836 individuals to add to a growing body of evidence that higher physical activity levels in the general population are associated with a lower risk of ALS. This study incorporates both subjectively reported and objective device measurements of physical activity in investigating...

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