BMJ Neurology Open最新文献

Sjögren's disease (SjD) is a chronic autoimmune connective tissue disorder primarily affecting the salivary and lacrimal glands. Extra-glandular involvement may occur, sometimes preceding the diagnosis of SjD or in the absence of sicca symptoms, contributing to diagnostic delay. Central nervous system (CNS) manifestations have been reported in SjD, though establishing a causal relationship is challenging given possible overlapping neuroinflammatory and autoimmune aetiologies. We report two patients who presented with acute encephalitis and new-onset refractory status epilepticus (NORSE), in whom features supportive of primary SjD were subsequently identified. Both patients underwent extensive evaluation that excluded infectious causes, other systemic autoimmune connective tissue diseases and known autoantibody-mediated forms of autoimmune encephalitis. These cases highlight the importance of considering systemic autoimmune diseases in the evaluation of unexplained encephalitis and NORSE, and support the early use of immunotherapy when an immune-mediated pathology is suspected.

Background: Dysphagia is common in amyotrophic lateral sclerosis (ALS), contributing to malnutrition and accelerated disease progression. Although early nutritional intervention is recommended, the optimal timing for percutaneous endoscopic gastrostomy (PEG) placement remains uncertain. This study aimed to develop and validate simple prediction models, accessible via an online calculator, to identify ALS patients likely to require PEG within 6 months.

Methods: We conducted a retrospective cohort study including ALS patients followed at three Italian reference centres between February 2018 and October 2023. Predictors of PEG placement within 6 months were identified using univariate and multivariable binary logistic regression models. Prediction models were developed following Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines and underwent both internal and external validation.

Results: In the development cohort (n=263; median age 63.8 years), 138 patients (52.5%) underwent PEG within 6 months. Three models were developed: the Anamnestic Prediction Model, based on age, onset site and non-invasive ventilation (NIV), showed fair predictive performance. The Anamnestic and Functional Prediction Model, incorporating age, bulbar subscore of Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-r) and forced vital capacity (%), demonstrated strong predictive performance (Brier score: 0.1230), excellent discrimination (concordance index (c-index) 0.91) and good calibration (Hosmer-Lemeshow p=0.59). The Anamnestic and Nutritional Prediction Model, including age, onset site, NIV, body mass index and weight loss, showed good predictive performance (Brier score: 0.1719), discrimination (c-index 0.81) and calibration (Hosmer-Lemeshow p=0.48). These findings were confirmed in an external validation cohort of 116 ALS patients.

Conclusions: The prediction models provide accurate, easily implementable tools to predict PEG need within 6 months, enabling timely nutritional interventions that may improve outcomes and care quality in ALS.

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare genetic disorder impairing cerebral glucose transport, leading to variable neurological symptoms in which adult care remains underexplored. This study aims to characterise adult phenotypes, identify unmet needs and inform a person-centred care model.

Methods: 32 adults with genetically confirmed GLUT1DS were retrospectively evaluated at two centres in Milan, Italy. Clinical history, diagnostic data, treatment and follow-up information were systematically collected. 19 patients underwent extended assessments including cognitive, neuropsychiatric, sleep, adaptive functioning and quality of life evaluations. Nine also participated in psychological interviews.

Results: The cohort included 68.8% female (median age: 32 years). Median age at symptom onset was 2 years, with a diagnostic delay of 18 years. 62% of individuals received a diagnosis in adulthood, with 31% diagnosed only after their child was identified. Except for two cases, all exhibited in their clinical history typical GLUT1DS symptoms that were either unrecognised or too mild to prompt medical attention. Psychosocial health issues were identified in 42% of cases, with emotional disturbances affecting 53% and social life impairments in 42%; physical health concerns in 32%.

Conclusions: Diagnostic delay in adults with GLUT1DS is more likely due to limited clinical awareness than to atypical presentations. The most effective model of care for individuals with GLUT1DS might be multidisciplinary involving paediatric and adult neurologists, rehabilitation professionals, clinical psychologists, clinical nutritionists and dietitians to support motor, cognitive and emotional functioning, thereby promoting autonomy, improving quality of life and addressing challenges associated with ketogenic diet adherence.

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.