BMJ Neurology Open最新文献

Background and objectives: Cardioembolic stroke (CES) appears to be a rare cause of stroke (4%-9%) in people living with HIV (PLWH) in sub-Saharan Africa (SSA). However, due to limited access to diagnostic resources, this may be an underestimate. It is also unclear which cardiac pathologies are the major contributors to CES in this region. We sought to determine the prevalence and aetiology of CES in PLWH and to determine whether there are any differences compared with HIV negative stroke patients.

Methods: This cross-sectional study recruited PLWH with new-onset stroke at a quaternary-level hospital in Johannesburg, South Africa, from 2014 to 2017, and compared them to age-matched and sex-matched HIV negative stroke patients. Comprehensive investigations were performed to determine the underlying stroke aetiology, including electrocardiography, echocardiography, CT angiography and cerebrospinal fluid examination.

Results: 85 PLWH with ischaemic stroke were recruited and compared with 109 HIV negative controls. CES was identified in 17/85 (20.0%) of PLWH. These patients had more severe strokes than PLWH with non-CES (National Institutes of Health Stroke Scale score 14.9±6.7 vs 11.7±5.4, p=0.04). Cardiomyopathy was the predominant cardiac pathology in PLWH (76.4% vs 45.5% in HIV negative, p=0.04) while valvulopathy was more common in HIV negative patients (42.4% vs 11.8% in PLWH, p=0.03). Arrhythmia (n=1) and ischaemic heart disease (n=1) were uncommon in PLWH.

Conclusion: CES is underdiagnosed in SSA and is more severe than non-CES. The identification of cardiomyopathy as the predominant underlying cardiac pathology may assist to target resources towards its detection using accessible cost-effective biomarkers.

Background: Machine learning (ML) can differentiate papilloedema from normal optic discs using fundus photos. Currently, papilloedema severity is assessed using the descriptive, ordinal Frisén scale. We hypothesise that ML can quantify papilloedema and detect a treatment effect on papilloedema due to idiopathic intracranial hypertension.

Methods: We trained a convolutional neural network to assign a Frisén grade to fundus photos taken from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). We applied modified subject-based fivefold cross-validation to grade 2979 longitudinal images from 158 participants' study eyes (ie, the eye with the worst mean deviation) in the IIHTT. Compared with the human expert-determined grades, we hypothesise that ML-estimated grades can also demonstrate differential changes over time in the IIHTT study eyes between the treatment (acetazolamide (ACZ) plus diet) and placebo (diet only) groups.

Findings: The average ML-determined grade correlated strongly with the reference standard (r=0.76, p<0.001; mean absolute error=0.54). At the presentation, treatment groups had similar expert-determined and ML-determined Frisén grades. The average ML-determined grade for the ACZ group (1.7, 95% CI 1.5 to 1.8) was significantly lower (p=0.0003) than for the placebo group (2.3, 95% CI 2.0 to 2.5) at the 6-month trial outcome.

Interpretation: Supervised ML of fundus photos quantified the degree of papilloedema and changes over time reflecting the effects of ACZ. Given the increasing availability of fundus photography, neurologists will be able to use ML to quantify papilloedema on a continuous scale that incorporates the features of the Frisén grade to monitor interventions.

Background: Accurate outcome predictions for patients who had ischaemic stroke with successful reperfusion after endovascular thrombectomy (EVT) may improve patient treatment and care. Our study developed prediction models for key clinical outcomes in patients with successful reperfusion following EVT in an Australian population.

Methods: The study included all patients who had ischaemic stroke with occlusion in the proximal anterior cerebral circulation and successful reperfusion post-EVT over a 7-year period. Multivariable logistic regression and Cox regression models, incorporating bootstrap and multiple imputation techniques, were used to identify predictors and develop models for key clinical outcomes: 3-month poor functional status; 30-day, 1-year and 3-year mortality; survival time.

Results: A total of 978 patients were included in the analyses. Predictors associated with one or more poor outcomes include: older age (ORs for every 5-year increase: 1.22-1.40), higher premorbid functional modified Rankin Scale (ORs: 1.31-1.75), higher baseline National Institutes of Health Stroke Scale (ORs: 1.05-1.07) score, higher blood glucose (ORs: 1.08-1.19), larger core volume (ORs for every 10 mL increase: 1.10-1.22), pre-EVT thrombolytic therapy (ORs: 0.44-0.56), history of heart failure (outcome: 30-day mortality, OR=1.87), interhospital transfer (ORs: 1.42 to 1.53), non-rural/regional stroke onset (outcome: functional dependency, OR=0.64), longer onset-to-groin puncture time (outcome: 3-year mortality, OR=1.08) and atherosclerosis-caused stroke (outcome: functional dependency, OR=1.68). The models using these predictors demonstrated moderate predictive abilities (area under the receiver operating characteristic curve range: 0.752-0.796).

Conclusion: Our models using real-world predictors assessed at hospital admission showed satisfactory performance in predicting poor functional outcomes and short-term and long-term mortality for patients with successful reperfusion following EVT. These can be used to inform EVT treatment provision and consent.

Background: Ocrelizumab, a humanised anti-CD20 monoclonal, is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS). The long-term safety of B-cell depletion in RRMS, however, is uncertain and there are no data on dose reduction of ocrelizumab as a risk mitigation strategy. This study aimed to evaluate the effectiveness and safety of reducing ocrelizumab dose from 600 to 300 mg in patients with RRMS.

Method: Data were collected through the Townsville neurology service. Following the standard randomised controlled trial regimen of 600 mg every 6 months for 2 years, sequential patients consented to dose reduction to 300 mg every 6 months. Patients were included if they were diagnosed with RRMS and received at least one reduced dose of ocrelizumab. Relapse, disability progression, new MRI lesions, CD19⁺ cell counts and immunoglobulin concentrations were analysed.

Results: A total of 35 patients, treated with 177 full and 107 reduced doses, were included. The mean follow-up on reduced dose was 17 (1-31) months. We observed no relapses or new MRI activity in the cohort receiving the reduced dose, accompanied by persistent CD19+B cell depletion (≤0.05×10⁹/L). Mean IgG, IgA and IgM levels remained stable throughout the study. No new safety concerns arose.

Conclusions: In this single-centre observational study, dose reduction of ocrelizumab from 600 to 300 mg every 6 months after 2 years appeared to maintain efficacy in terms of new inflammatory disease activity. A randomised trial may be warranted to confirm this and explore the impact of dose reduction on long-term safety.

Background: Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation.

Methodology: Next-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias.

Results: We here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification.

Conclusion: Dystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.

Introduction: Recently, there have been a few reports of atypical post-coronavirus disease 2019 (COVID-19) myelopathy manifesting tract-specific lesions similar to those due to vitamin B₁₂ deficiency. However, the precise characteristics of imaging or clinical course remain not well understood.

Methods: A retrospective analysis of the clinical and imaging characteristics of four patients who were referred to our hospital with a unique post-COVID-19 myelopathy was performed.

Results: Four-to-six weeks following COVID-19 infection in the summer of 2023, four middle-aged men developed paraparesis, hypo/dysesthesia and bladder/bowel disturbance, suggesting myelopathy. Although spinal MRI showed no abnormalities in the early stages, tract-specific longitudinal lesions along the dorsal and lateral columns became apparent as the symptoms progressed. Owing to the lack of MRI findings at the early stage, all cases were challenging to diagnose. However, the patients remained partially responsive to aggressive immunosuppressive therapies, even in the advanced stage.

Discussion: We termed these tract-specific longitudinal lesions in the presented case series 'Grasshopper sign' because brain coronal and spine axial MRI findings looked like a grasshopper's antennae and face. Early identification of the characteristic MRI abnormality could allow for early intervention using intensive immunosuppressive therapy, which could improve patient outcomes.