BMJ Neurology Open最新文献

Background: Increased use of healthcare before multiple sclerosis (MS) onset indicates a prodromal phase. Data on the prodromal phase of paediatric-onset MS (PoMS) are sparse, especially regarding age-specific and sex-specific characteristics. The objective of this study was to examine healthcare use by age and sex before PoMS clinical onset.

Methods: Individuals with MS with symptom onset before age 18 were identified in the Swedish MS registry. Rates of hospitalisations, outpatient visits and prescriptions dispensed were compared with a matched non-MS cohort for up to 16 years before MS onset, categorised by age at onset (12-15 and 16-17 years) and sex.

Results: We included 233 PoMS and 1151 matched individuals. Compared with the matched cohort, females with PoMS exhibited higher annual rates of outpatient visits in the years preceding MS onset for neoplasms (rate ratios (RRs) 3.44-5.73) while males had higher rates for skin-related visits (RRs 6.00-11.00) and prescription dispensations for corticosteroids for dermatological use (year -1, RR 3.12; 95% CI 1.01 to 9.68). Older teenagers with MS had higher visit rates for neoplasms (RRs 3.98-8.70), while younger teenagers had higher nervous system-related visit rates (RRs 4.51-5.97) before MS onset.

Conclusions: Individuals with PoMS showed age-specific and sex-specific increases in healthcare use before symptom onset, including skin-related visits in males and neoplasm-related visits for females and 16-17 year-olds. These results can help guide our understanding of MS mechanisms and may aid in earlier detection of MS in the paediatric population.

Background: Functional movement disorders (FMDs) are commonly classified along canonical non-ataxic movement disorder patterns, creating a potential blind spot for frequently observed ataxia-like presentations. At the same time, normal diagnostic findings and episodic symptom variability in some cerebellar ataxias predispose to an incorrect FMD diagnosis.

Cases: We present three cases that illustrate pitfalls in the differential diagnosis of ataxia. First, a patient treated for presumed immune-mediated cerebellar ataxia was diagnosed with FMD based on clinical signs. Next, a patient with intermittent and inconsistent symptoms was diagnosed with FMD after extensive exclusionary workup, but was then found to have a novel type of spinocerebellar ataxia. The third patient had a genetically confirmed spinocerebellar ataxia but developed additional functional motor symptoms.

Conclusion: Differentiating cerebellar ataxias from FMDs and recognising mixed presentations is essential. Enhanced clinical awareness and systematic diagnostic evaluation are crucial to avoid misdiagnosis and ensure optimal treatment.

Introduction: Targeting progressive multiple sclerosis (MS) addresses the current single biggest unmet need in the MS therapeutic landscape and anti-Epstein-Barr virus (EBV) therapy potentially strikes at the root cause. The SpironolacTone and famciclOvir in the treatment of Progressive MS to prevent disability progression (STOP-MS) trial has been developed to assess anti-EBV therapies in the treatment of progressive MS.

Methods and analysis: STOP-MS is a multi-arm, multi-stage, randomised, double-blind, placebo-controlled trial testing spironolactone and famciclovir to prevent disability progression in MS. Australians with progressive forms of MS, aged 25 to 70 years with established disability, are eligible. Recruitment commenced in March 2025 and the first participant was enrolled on 15 April 2025. The sample size for STOP-MS is 150 in stage 1 and 300 in stage 2. In stage 1, the composite primary outcome measures will be reduction of EBV DNA in saliva and serum EBV nuclear antigen-1 antibody titres. Minimum criteria for consideration of progression to stage 2 will be a 10% reduction in the composite outcome measure. In stage 2, the primary outcome measure will be 6-month confirmed disability progression analysed using Cox-proportional hazards.

Trial registration number: The STOP-MS trial has been acknowledged by the Therapeutics Goods Administration under the Clinical Trial Notification scheme (CT-2023-CTN-03 505-1) and is registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623000849695).

Background: Anti-gamma-aminobutyric acid B receptor (GABA-B R) encephalitis is an uncommon autoimmune disorder typically presenting with seizures, memory impairment and a frequent paraneoplastic association with small cell lung carcinoma. Although GABA-B Rs are expressed in cardiac tissue, extracerebral manifestations have rarely been described.

Case presentation: A 65-year-old man presented with status epilepticus. Cerebrospinal fluid (CSF) analysis revealed mild lymphocytic pleocytosis and type 3 oligoclonal bands. Anti-GABA-B R antibodies were detected in serum and CSF, confirming the diagnosis of autoimmune encephalitis. The patient improved after high-dose intravenous corticosteroids but died unexpectedly during recovery. Autopsy revealed perivascular CD3-positive lymphocytic infiltration in the brain and meninges, consistent with autoimmune encephalitis, and metastatic neuroendocrine carcinoma compatible with a pulmonary primary. Notably, CD3-positive lymphocytic infiltration was also found within myocardial fibres, consistent with lymphocytic myocarditis.

Conclusions: This case broadens the recognised spectrum of anti-GABA-B R encephalitis and raises the possibility of cardiac involvement in this disorder. The presence of GABA-B Rs in cardiomyocytes offers a potential link between receptor autoimmunity and myocardial inflammation. Although causality cannot be established, these findings suggest that cardiac monitoring may be advisable in patients with anti-GABA-B R encephalitis, particularly in paraneoplastic contexts.

Background: Health literacy (HL) is a key determinant of health outcomes, especially in chronic neurological diseases such as multiple sclerosis (MS). Insufficient HL may impair the ability of patients to manage their condition, reduce treatment adherence and increase the use of healthcare.

Objective: To identify factors influencing HL among individuals with MS and to explore its association with illness perception and medication-related behaviours.

Methods: Between April and September 2023, we consecutively enrolled 330 patients with MS from a single outpatient clinic. We included individuals aged 18-65 years with functional literacy, and we did not exclude participants based on MS subtype, education level, disability status or treatment characteristics. We assessed HL using the Newest Vital Sign, cognition using the Montreal Cognitive Assessment (MoCA), emotional status using the Hospital Anxiety and Depression Scale, and illness perception using the Brief Illness Perception Questionnaire (BIP-Q). We also evaluated self-reported medication adherence and perceived treatment benefits. After excluding 11 participants with incomplete data, we analysed 319 complete responses in accordance with Strengthening the Reporting of Observational Studies in Epidemiology guidelines.

Results: Overall, 49.7% of participants demonstrated adequate HL. The HL correlated positively with MoCA scores and education (path coefficients: 0.117, 0.114) and negatively with disease duration, age and depression (-0.023,-0.029, -0.085). HL was positively associated with illness perception (BIP-Q coefficient: 1.558). The model explained 35.6% of the variance in HL and 5.7% in illness perception (R²=0.356; 0.057).

Conclusion: Our findings suggest that routine HL assessment and targeted educational interventions may enhance understanding, adherence and informed decision-making, ultimately improving disease management and outcomes in MS.

Epilepsy is a chronic, neurological disorder that affects 65 million people worldwide. Two-thirds are estimated to become seizure free with anti-seizure medications (ASMs), while one-third will ultimately develop drug-resistant epilepsy (DRE). Although >30 ASMs are now available, treatment outcomes among all epilepsies do not appear to have improved. There is a paucity of prognostic evidence specific to focal epilepsies, despite focal epilepsy being one of the most common forms of epilepsy and an independent risk factor for developing DRE. Accurate prognostication has largely been limited by variable definitions of treatment response in the literature. Use of the current International League Against Epilepsy treatment response definitions in research studies and clinical practice may improve the quality of prognostic evidence, as well as help identify important phenotypes of treatment responsiveness. This is particularly important as pharmacological treatments for epilepsy continue to expand without clear evidence we are improving outcomes.

Objective: Intravenous thrombolysis is an effective method in treating acute ischaemic stroke, with several studies reporting improved outcomes and reduced mortality rates. However, there are limited data on whether thrombolysis is effective in treating different ischaemic stroke subtypes in the Middle East and North African region.

Methods: Data of cortical and lacunar patients who received intravenous thrombolysis from the Qatar Stroke Registry were retrospectively analysed from April 2014 to January 2025. Patients were matched 1:2 for age and admission National Institute of Health Stroke Scale (NIHSS).

Results: Patients with cortical stroke who received recombinant tissue-type plasminogen activator (rt-PA) had a significantly lower proportion of a poor clinical outcome at 90 days (modified Rankin Scale (mRS) score of 3-6; 41.5% vs 50.5%, p=0.002), significantly lower NIHSS score at discharge (NIHSS score >10: 23.0% vs 33.9%, p<0.001), significantly lower proportion of mortality at 90 days (4.7% vs 8.2%, p=0.02) and significantly shorter length of stay (5.2 days vs 6.0 days, p=0.01) compared with controls. In terms of outcomes for patients with lacunar stroke, there were no significant differences compared with controls for their mRS score at 90 days (p=0.054), NIHSS score at discharge (p=0.21), mortality at 90 days (p=0.67) and length of stay (p=0.34). A multivariate conditional logistic regression model revealed that high admission NIHSS score (>10) was a significant predictor of a poor functional outcome at 90 days for cortical stroke post rt-PA (p<0.001), whereas for lacunar stroke, both high admission NIHSS score (>10) and symptom onset of >3 hours were identified as significant predictors of a poor functional outcome at 90 days post rt-PA (p=0.01 for both). History of diabetes mellitus and hypertension were also significant predictors of poor clinical outcome at 90 days, but this was only observed for cortical stroke (p<0.001 and p=0.003).

Conclusion: In this study, intravenous thrombolysis yielded significant clinical outcomes for patients with cortical stroke but not patients with lacunar stroke.

Background: Fluid biomarkers are emerging for diagnosis and monitoring in neurology. Epilepsy remains an exception, despite seizures being known to result in inflammation and altered levels of several brain proteins. We aimed to identify candidate biomarkers through a comprehensive proteomic analysis of proteins associated with brain disease or inflammation.

Methods: Cross-sectional analysis of plasma from adult participants in the PREDICT biobank study in Västra Götaland, Sweden. Participants aged 18-50 with epilepsy and seizures (n=88) were compared with those with epilepsy who had been seizure-free (n=88) for >1 year using four OlinkExplore384 panels, analysing 1447 proteins.

Results: Two machine-learning models, one linear and one non-linear, identified protein expression differences through feature selection, resulting in 51 unique proteins between the models. Twenty-three proteins were considered differentially expressed after false discovery rate adjustment (p≤0.05), including neurofilament light and several cytokines. Protein-protein interaction (PPI) analysis identified clusters among 51 unique proteins, with the largest clusters primarily associated with inflammatory processes. In addition, machine learning-independent gene set enrichment analysis identified 34 gene sets, mainly related to immune and inflammatory processes, that were also enriched in participants with seizures.

Conclusions: Persons with epilepsy and seizures had different plasma protein profiles compared with those seizure-free, primarily suggesting altered inflammatory/immune processes. This fits well with growing evidence of inflammation as a key process in epilepsy. In addition to new therapeutic targets, immune processes need further exploration as candidate biomarkers for monitoring of treatment response in epilepsy.

Background: Ocular myasthenia gravis (oMG), characterised by ptosis and diplopia, may progress to generalised MG (gMG). Thymectomy is established for seropositive gMG, but its role in oMG remains unclear. Robotic-assisted thoracoscopic surgery (RATS) offers minimally invasive advantages, yet outcomes in oMG are understudied. This case series describes the outcomes of seven patients at University College London Hospitals (UCLH) (2019-2025) undergoing robotic thymectomy for oMG.

Methods: We describe seven oMG patients undergoing robotic thymectomy at UCLH (2019-2025), focusing on improvement in daily life using the MG activities of daily living (MG-ADL) score and medication reduction.

Results: Patients showed significant pyridostigmine reduction (mean decrease: 246 mg) and improved MG-ADL scores (mean=4.00 to 0.57) with no major complications. No patients progressed to gMG.

Conclusion: We saw robotic thymectomy (RATS) reduce pyridostigmine dependence and improve quality of life (MG-ADL) in the seven oMG patients, with no complications. These cases demonstrated successful cases of RATS as a transformative, minimally invasive option for early MG. While thymectomy may reduce the risk of generalisation, further multicentre studies are needed. Careful patient selection remains critical, but RATS may expand feasibility in oMG.

Introduction: People with multiple sclerosis (pwMS) receiving B-cell depleting disease-modifying therapy (BCD-DMT) are vulnerable to severe COVID-19. Data on vaccine immunogenicity in this patient group are incomplete. In the context of the rapid evolution of SARS-CoV-2 2020-22, we compared vaccine responses in pwMS and healthy vaccinated adults (HVA) after three doses of messenger RNA vaccine encoding Ancestral SARS-CoV-2 Spike.

Methods: In this prospective observational cohort study, we collected serum from 226 pwMS prevaccine and postvaccine and quantified neutralising antibody titres (nAbT) in a high-throughput live virus assay against SARS-CoV-2 Ancestral, Alpha, Delta, Omicron BA.1, BA.2 and BA.5. We compared nAbT in pwMS and HVA, matched by age, sex, vaccine type, number of doses and time since exposure, using Wilcoxon signed-rank and χ² tests. We further investigated nAbT vaccine response in pwMS on BCD-DMTs or non-depleting DMTs.

Results: Prior to third vaccination, nAbTs against nearly all variants tested were significantly lower (p<0.05) in pwMS taking BCD therapy than those in HVA or B-cell replete pwMS, and were not significantly boosted following vaccination. In contrast, B-cell replete pwMS versus HVAs exhibited equivalent prevaccination nAbTs against all variants, which were comparably boosted against most variants following vaccination. Consequently, differences in nAbTs against all variants tested were further magnified between B-cell replete and B-cell depleted pwMS post-third vaccination. Across the entire cohort, there were no COVID-19 hospitalisations or deaths. Notably, sera collected prior to the pandemic from pwMS demonstrated pre-existing, pan-coronavirus neutralising activity against seasonal HCoV-OC43 and SARS-CoV-2 variants.

Conclusions: PwMS taking BCD therapy have limited antibody boosting following repeated COVID-19 vaccination. However, the absence of severe outcomes in pwMS, despite reduced immunogenicity, suggests a lower threshold for effective protection than previously reported. These findings support more nuanced risk stratification in clinical policy.