Journal of Neurology最新文献

Amyotrophic lateral sclerosis (ALS) is more prevalent in males than in females. However, it is unclear whether the difference in sex ratio is observed similarly in sporadic compared to familial ALS. Here, we conducted a systematic review to investigate the differences in sex ratio between familial and sporadic ALS. Following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines, this study searched Ovid MEDLINE, Embase, Emcare, SCOPUS and Cochrane databases. We used a random-effects meta-analysis to estimate sex ratios in a total of 9269 ALS patients (4135 female, 5134 male) across 20 included studies. We confirmed that ALS is more prevalent in males than in females (sex ratio: 1.25 (95%CI 1.14-1.37). However, when we stratified the analyses, the sex ratio was only different in sporadic ALS. Male-to-female ratios were 1.29 (95% CI 1.16-1.42) for sporadic ALS and 1.05 (95% CI 0.93-1.18) for familial ALS. A further analysis showed a pooled risk ratio of 1.07 (95% CI 1.00-1.15), indicating a 7% higher likelihood of males being diagnosed with sporadic rather than familial ALS. These findings highlight the importance of considering sex-specific factors in ALS research and clinical practice.

Background: Neurological disorders, a leading cause of global disability, often cause debilitating dizziness and imbalance. While subjective symptoms are well-documented, the actual prevalence of vestibulo-ocular reflex (VOR) dysfunction in patients with central nervous system (CNS) damage remains unclear due to inconsistent primary studies. This research aims to determine the prevalence of VOR gain dysfunction, as measured by the video Head Impulse Test (vHIT), across neurological disorders.

Methods: Our systematic review searched MEDLINE, CENTRAL, CINAHL, Scopus, ClinicalTrials.gov, and the WHO ICTRP for original articles from 2009 to September 2025. The JBI Checklist for prevalence studies was used to assess the methodological quality, and descriptive analyses were performed, followed by a meta-analysis of proportions using a random-intercept logistic regression model.

Results: We included 48 studies, of which three reported on the same or overlapping samples. Thus, 45 unique studies (1604 participants, 792 females, mean age 56) were described. A meta-analysis of 33 studies (1129 participants) found an overall prevalence of vestibular dysfunction of 48% (95% CI 31-67%). Given the high heterogeneity, we performed subgroup analyses by condition. We found a pooled prevalence of 98% for CANVAS, 73% for ataxia, 44% for Parkinson's disease, 59% for multiple sclerosis, 15% for traumatic brain injury, 5% for multiple system atrophy, and 77% for superficial siderosis.

Conclusion: Isolated semicircular canal dysfunctions, as documented using vHIT, are prevalent in neurological disorders. Future research must elucidate their etiology and diagnostic potential, utilizing comprehensive vestibular assessments. Eventually, these findings should be translated into improved, evidence-based rehabilitation strategies.

Prospero registration: CRD42024575542.

Spinal muscular atrophy (SMA) is a rare inherited disorder that results in skeletal muscle wasting and weakness with a varying degree of severity. Pregnancy is associated with several changes in respiratory muscle function and respiratory physiology, which can compromise breathing leading to complications during pregnancy and delivery. Pregnant women with SMA are therefore considered to be a high-risk obstetric group. Due to the rare nature of the condition, it is infrequently encountered in pregnancy and this highlights the clinical importance of reporting this current case series. We report, in this retrospective case series, the outcomes of eight pregnancies in six women living with SMA, including, to our knowledge, the first reported successful pregnancy in a woman with SMA type-1, managed in our tertiary multi-professional and multi-speciality centre. All pregnancies, over an 18-year period, resulted in healthy live births between 30 and 39 weeks of gestation, six were pre-term (before 37 weeks gestation) and two were term. Although there were no maternal deaths, four women had a deterioration in respiratory function during the second trimester. All, but one returned to their pre-pregnancy state by three months postpartum. One had an obstetric-related post-partum complication and returned to pre-pregnancy baseline by the first year postpartum. Our case series, of a rare neuromuscular condition in pregnancy, strongly supports that appropriate multi-professional and multi-speciality care for pregnant women living with SMA enhances the outcome for both mother and baby. Indeed, two of our women had the confidence to proceed with a second pregnancy, both of which concluded in good outcomes.

Background: The weekend warrior (WW) exercise pattern, where individuals accumulate the recommended 150-min moderate-to-vigorous physical activity (MVPA) over 1-2 days, has become a popular alternative to daily physical activity routines. This study investigates the association of WW and other leisure-time physical activity patterns with the risk of neurological diseases, specifically sleep disorders, migraines, and epilepsy.

Methods: This study includes data from 93,684 participants, obtained from the UK Biobank. MVPA patterns were categorized into inactive, regularly active, and WW groups. Cox proportional hazards models, restricted cubic splines (RCS), and Kaplan-Meier curves were used to assess the impact of exercise patterns on the risk of neurological diseases.

Results: Both the WW and regularly active groups exhibited significantly lower risks for sleep disorders, migraine, and epilepsy than the inactive group. In the fully adjusted analyses, weekend warrior activity was associated with a 16.8% lower risk of sleep disorders, a 23.9% lower risk of migraine, and a 25.3% lower risk of epilepsy compared with inactivity. The results of RCS curves for these disorders further supported these findings.

Conclusions: The WW pattern offers similar benefits to daily exercise in reducing the risk of neurological disorders, particularly sleep disorders, migraine, and epilepsy. This finding suggests that WW activity may be a practical and flexible approach to disease prevention in modern societies.

Background: Focal hand dystonia (FHD) is a task-specific movement disorder characterized by involuntary muscle contractions during skilled hand use. Impaired intracortical inhibition is a core feature of FHD, yet its relationship to functional brain activity during motor tasks remains poorly understood. This study combined transcranial magnetic stimulation (TMS) and functional MRI (fMRI) to investigate the relationship between intracortical inhibition, as measured by the cortical silent period (cSP), and task-based brain activation in individuals with FHD.

Methods: Sixteen individuals with FHD and 18 age-matched healthy controls completed cSP assessments and fMRI. Participants performed self-paced finger tapping with each hand separately. For FHD participants with left-hand symptoms (n = 4), left-right labels were flipped during analysis so that right-hand data represented the symptomatic hand and left-hand data represented the non-symptomatic hand across all participants. We analyzed activation in sensorimotor regions and tested voxel-wise correlations between cSP duration and BOLD responses.

Results: FHD participants demonstrated greater activation in the inferior parietal lobule (IPL) within the posterior parietal cortex (PPC) during both right- and left-hand finger tapping. Notably, during left-finger tapping (non-symptomatic hand), cSP duration positively correlated with cerebellar activation, suggesting altered integration of inhibitory circuits during motor execution. No such correlations were found during right-finger tapping (symptomatic hand) or for control participants.

Conclusion: These findings suggest that individuals with FHD may selectively recruit cerebellar sensorimotor circuits to modulate inhibition during movement of the non-symptomatic hand, though this pattern was not observed during movement of the symptomatic hand. The cerebellum may play a central role in adaptive motor control in FHD. Future work should leverage symptom-inducing tasks and alternative inhibitory markers to further clarify these mechanisms.

Background: In a clinically-heterogeneous disease such as ALS, it is crucial to identify early disease changes that impair real-world functioning. The lack of consensus across clinical approaches, coupled with the subjectiveness of their evaluation, impedes our understanding of disease processes underlying early and advanced disease. This study presents neuroimaging as a potential supplementary approach that provides objectivity to the identification and evaluation of disease stage-specific ALS subgroups.

Methods: Cerebral functional connectivity and its association with clinical function was evaluated in 174 ALS patients and 165 healthy controls enrolled in the Canadian ALS Neuroimaging Consortium (CALSNIC). Participants were subgrouped using two approaches: (1) a data-driven hierarchical clustering of cerebral activation and 2) contemporary clinical criteria. The data-driven approach utilized data from resting-state functional magnetic resonance imaging. The clinical approach utilized three clinical subgrouping methods - two derived from trial enrollment criteria for the drugs Riluzole and Edaravone, and the third on the median disease progression rate of the patient sample.

Results: Each subgrouping approach identified two patient subgroups with different symptom durations, disease progression rates, and cognitive/motor/lung functions - albeit with differences across approaches. The data-driven approach identified greater spatial extents of cerebral connectivity alterations compared to the clinical approaches.

Conclusion: Observations of clinical and cerebral connectivity differences were specific to the stratification approach. Given the ability of the data-driven approach to identify alterations in both clinical and cerebral function corresponding to disease stage, this approach presents a potential biomarker for patient stratification, clinical trial enrichment, disease and therapeutic monitoring.

Background: While atrial fibrillation is the leading cause of cardioembolic stroke in elderly patients, the underlying cardiac substrate often remains unidentified. Transthyretin cardiac amyloidosis (ATTR-CA), a treatable cardiomyopathy affecting predominantly elderly males, causes atrial fibrillation and carries high thromboembolic risk but remains largely unrecognized among stroke physicians. With disease-modifying therapies now available, identifying ATTR-CA as a cause of cardioembolic stroke has become increasingly important.

Methods: To determine ATTR-CA prevalence and identify clinical indicators enabling systematic screening for this underdiagnosed cardiomyopathy, we performed a single-center retrospective cohort study of 143 consecutive patients with cardioembolic stroke among 430 ischemic stroke admissions. Patients with clinical suspicion underwent ⁹⁹ᵐTc-pyrophosphate scintigraphy for ATTR-CA diagnosis.

Results: ATTR-CA was diagnosed in 14/143 patients (9.8%; 95% confidence interval: 5.4-16.0%). Notably, 50% of patients were newly diagnosed with ATTR-CA following stroke presentation. Compared with non-CA patients (n = 129), ATTR-CA patients demonstrated: male predominance (79% vs. 49%, p = 0.048), two-fold higher levels of troponin T (median 0.058 vs. 0.029 ng/mL, p = 0.035), characteristic biventricular hypertrophy, reduced left ventricular ejection fraction, and elevated E/e' ratio. Musculoskeletal manifestations, including spinal stenosis (57%), carpal tunnel syndrome (57%), and Popeye sign (75%), were highly prevalent.

Conclusions: ATTR-CA was found in nearly 10% of elderly patients with cardioembolic stroke, with half remaining undiagnosed until stroke presentation. Cardiac hypertrophy, elevated troponin levels, and musculoskeletal manifestations provide practical screening indicators for stroke physicians. Given the availability of disease-modifying therapies, these findings emphasize the importance of systematic ATTR-CA screening in cardioembolic stroke populations.

Background: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder, with age at onset (AAO) influenced by genetic and environmental factors. This study aimed to (i) examine temporal trends in PD AAO over the past four decades in a large tertiary care cohort; and (ii) identify independent associations between AAO and a comprehensive set of demographics, cardiovascular/dysmetabolic, lifestyle, and environmental variables.

Methods: We conducted a retrospective observational study of 13,220 individuals diagnosed with PD between 1998 and 2024 at a tertiary referral center in Italy, excluding genetically confirmed cases. Demographic, clinical, and exposure data were collected via questionnaires and interviews. Temporal trends in AAO were analysed in relation to national population ageing. Independent predictors of AAO were identified using multivariable linear regression with cross-validation and multiple imputation. Age- and sex-stratified analyses were also performed.

Results: AAO increased over time in parallel with demographic ageing (R² = 0.94), without evidence of additional temporal acceleration (P = 0.852). An earlier AAO was independently associated with a positive family history of PD (β = -2.96, P < 0.0001), pollutant exposure (β = -3.50, P < 0.0001), and higher education level (β = -0.52, P < 0.0001). In contrast, type 2 diabetes mellitus (β =  + 2.63, P < 0.0001) and hypertension (β =  + 2.24, P < 0.0001) were associated with later onset. Among women, later menarche was linked to delayed AAO (β =  + 0.60, P < 0.0001).

Conclusions: While demographic ageing largely accounts for the temporal increase in AAO, modifiable exposures, particularly cardiovascular/dysmetabolic comorbidities and environmental toxins, can significantly influence disease timing, though causal interpretation is limited by accumulation bias.