BMJ Neurology Open最新文献

Background: Multiple sclerosis (MS) involves cortical injury, including cortical lesion (CL) development. Ibudilast treatment was found to slow progression of whole brain and cortical atrophy, but the effect of ibudilast on CLs is unknown. The present study aims to evaluate the treatment effect of ibudilast on CL development and whether the effect of ibudilast on brain atrophy is modified by CLs in primary-progressive MS (PPMS).

Methods: In this longitudinal study, we analysed data of 102 people with PPMS (ibudilast: n=49; placebo: n=53) from the Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis. CLs were identified on artificial intelligence-generated double inversion-recovery images created from T1 and T2 images at 3T MRI and rated at baseline and week 96. Atrophy was measured by cortical thickness and brain parenchymal fraction.

Results: CLs were detected in all participants with PPMS with a median count of 22 (11-34) in the ibudilast group and 28 (13-44) in the placebo group. At baseline, treatment groups did not differ in any brain volume measure or CL count. Higher CL counts at baseline were associated with higher CL formation during follow-up (B(95% CI)=0.20 (0.12 to 0.29), p<0.001), independent of ibudilast treatment.Change in CL count did not differ between treatment groups (mean difference (SD)=0.07 (0.29), p=0.364). Protective effect of ibudilast on cortical thickness was more prominent in subjects with greater CL formation, but this relationship was not observed with whole brain atrophy.

Conclusions: Ibudilast treatment does not affect CL development in PPMS. Its protective effect on cortical thinning is more prominent with greater CL formation.

Trial registration number: NCT01982942.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially disabling complication of the neurotoxic chemotherapies; however, its occurrence is often unpredictable. We aimed to determine whether serum levels of neurofilament light chain (sNfL) could predict the onset and severity of CIPN, and whether sNfL levels were associated with other clinical factors in people with cancer.

Methods: Adult patients (>18 years) prescribed at least four cycles of oxaliplatin, cisplatin, docetaxel or paclitaxel were clinically assessed and had blood taken for sNfL analysis at baseline and prior to each cycle. Peak sNfL was compared with clinical characteristics and Total Neuropathy Score-Clinical version (TNSc), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, V.4.03) and CIPN-Rasch-built Overall Disability Scale (CIPN-RODS). Individual patient trends in sNfL and TNSc were examined.

Results: 42 patients completed the study, with 36 receiving platinum agents and 6 receiving taxanes. Peak sNfL was higher with taxanes than with platinum agents (129.9 vs 31.0 pg/mL; p<0.0001). Higher peak sNfL was not associated with final TNSc, CTCAE or CIPN-RODS in patients receiving platinum agents. Using age-adjusted NfL z-scores, peak sNfL was associated with CIPN-RODS (rs=-0.45; p=0.012) and was higher in patients with a final CTCAE Grade of 2 compared with Grades 0-1 (p=0.015) but was not associated with final TNSc (rs=+0.37, p=0.050). In patients receiving platinum agents, higher peak sNfL was associated with death within 6 months of study entry (p=0.020). sNfL rose in conjunction with the increase in TNSc but did not precede clinical symptoms/signs of neuropathy in most patients.

Conclusion: Taxanes cause greater and sharper sNfL rises than platinum agents. Age-adjusted sNfL associates with neuropathy severity in platinum-treated patients; however, in most patients it is unable to detect early axonal damage before this is detectable with clinical examination.

Objective: Exercise-assistance strategies are useful in allowing mobility-impaired patients to access the benefits of exercise. This trial is the first of the Reviver device, which facilitates exercise via a novel strength and balance training mechanism. The objective was to examine the effect of a 12-week Reviver intervention on symptoms of Parkinsonism, and to pilot the randomised controlled trial design, including randomisation and acceptance of the exercise intervention.

Methods: This was a pilot, parallel-arm randomised controlled trial with assessor blinding. Participants (n=30: 22 with Parkinson's disease (PD) and 8 with atypical Parkinsonism conditions (AP)) were allocated to either experimental or control group. The experimental group received 24 sessions of 30 min on the Reviver over 12 weeks, the control group received their standard care. The Movement Disorders Society Unified Parkinson's Disease Rating Scale, and secondary outcomes (balance, gait, mobility, lower-body strength/coordination, tremor and grip strength) were acquired at endpoints the week prior to intervention commencement and the week after intervention termination. Recruitment progress, adherence to intervention, acceptability of intervention and adverse effects were also recorded.

Results: For the PD cohort, lower-body strength/coordination (5× Sit-To-Stand; b(95% CI)=-3.02 (-5.16 to -0.89), p=0.013), gait (self-selected walking speed; b=12.48 (2.18 to 22.78), p=0.029, stride length; b=9.75 (0.99 to 18.52), p=0.043) and backward walking speed (b=14.25 (1.93 to 26.57), p=0.038) were improved by the intervention. No significant effect of intervention on the outcome variables was found in the AP cohort. No serious adverse events were recorded. Median adherence to treatment was 95.8%.

Interpretation: This pilot trial indicates that the Reviver is a safe and well-tolerated exercise-assistance intervention. The Reviver showed some indications of benefit in our secondary measures for PD participants, but not in our primary outcome. This was a small sample, short duration pilot study, and further studies with larger samples and higher exercise volume are warranted to fully assess the safety and efficacy of the device.

Background: Primary central nervous system T-cell lymphoma (PCNSTL) is an exceptionally rare central nervous system lymphoma with limited clinical data. We present a large case review series of PCNSTL to summarise the clinical characteristics of this disease.

Methods: This study integrated 4 new cases of PCNSTL from our centre with 132 previously reported cases identified through a systematic search of PubMed, Cochrane Library and Web of Science databases.

Results: A total of 136 PCNSTL cases were identified, with a median age of 41 years (range 2-89 years), and a male-to-female ratio of 1.8:1. Peripheral T-cell lymphoma-not otherwise specified was the most prevalent pathological subtype. Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK+ALCL) predominated in men relative to the various subtypes. The cerebral hemispheres are the most frequent anatomical region involved (71.3%), followed by cerebellum (16.2%), basal ganglia (14.7%), brainstem (14.7%), meninges (11.8%) and corpus callosum (2.9%). Meningeal involvement was observed in nearly 50% of ALCL cases. Histopathologically, 31.8% of tumour cells (29/91) were small cell-dominated, 79.2% of the cases presented angiocentric growth pattern (57/72), and half of cases had a positive finding of cerebrospinal fluid (CSF) flow cytometry (7/14).

Conclusions: PCNSTL has a male predilection, particularly in ALK+ALCL. PCNSTL shows reduced basal ganglia and corpus callosum involvement relative to primary central nervous system B-cell lymphoma, but displays heightened meningeal tropism, especially in ALCL cases. Histopathological examination typically reveals prominent perivascular lymphocytic cuffing in PCNSTL. CSF flow cytometry could be considered a preferred method for a definite diagnosis of PCNSTL when brain biopsy is not possible.

Objectives: For people living with HIV (PLWH) and tuberculous meningitis (TBM), current studies on risk stratification and poor prognosis lack a clear optimal threshold. To address this gap, this study aims to identify an optimal immunological threshold for risk stratification and explore predictors of poor prognosis in this population.

Methods: We conducted a multicentre cross-sectional study enrolling PLWH with TBM from hospitals across eight provinces of China between January 2018 and December 2020. We extracted the demographic and clinical data, discharge outcomes, Medical Research Council staging and CD4⁺ T-lymphocyte count on admission. CD4 thresholds were determined using restricted cubic splines with knots at quintiles. Multivariable logistic regression of risk factors derived adjusted ORs with 95% CIs.

Results: A total of 201 participants were included in the study. Of these, 173 (86.1%) improved with treatment. Restricted cubic spline analysis identified CD4⁺ T-lymphocyte count <50 cells/µL as the optimal threshold for predicting poor TBM outcomes; the median CD4⁺ count was significantly lower in patients who deteriorated (40 cells/µL) than in those who improved (69 cells/µL). Multivariable logistic regression confirmed CD4⁺ T-lymphocyte count <50 cells/µL and elevated blood urea nitrogen (BUN) as independent risk factors for adverse outcomes.

Conclusions: In PLWH with TBM, a CD4⁺ T-cell count below 50 cells/µL defines a critical stratification threshold for clinical risk classification, with elevated BUN serving as an additional prognostic marker. These findings support the prioritisation of severely immunocompromised patients for targeted management and further mechanistic studies.

Pompe disease is a rare, inherited metabolic disorder characterised by lysosomal acid alpha-glucosidase deficiency. The disease is classified into infantile-onset and late-onset forms and is treated with enzyme replacement therapy. Currently, there are no standardised clinical management guidelines for Pompe disease in the UK. An expert panel of nine healthcare professionals with expertise in caring for patients with Pompe disease was convened. A review of the literature was performed for an overview of the available evidence and to identify gaps. This was used to develop survey questions for the steering committee to answer based on their clinical experience. Statements were drafted based on answers and voted on anonymously by the experts before being discussed during two meetings to reach consensus. Consensus was reached on how to diagnose Pompe disease in adult and paediatric patients, evaluations to assess disease progression and treatment effect and long-term management. These are the first UK-specific guidelines describing clinical management of Pompe disease.

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.