Journal of Neurology最新文献

Objective: This study aims to systematically evaluate the relationships and effects of different exercise modalities and exercise doses on the quality of life in patients with Parkinson's disease (PD).

Methods: Randomized controlled trials published from database inception to November 2025 were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library. The Cochrane Risk of Bias 2.0 (RoB 2.0) tool was used to assess the methodological quality of the included studies. Stata version 17.0 and R version 4.4.3 were used to analyze and compare the relationships and effects of different exercise modalities and exercise doses on quality of life in patients with PD.

Results: A total of 44 randomized controlled trials (RCTs), including 2,273 patients with PD, were analyzed. The network meta-analysis showed that aerobic exercise (AE) (SMD =  - 0.66; 95% CI: - 0.93 to - 0.39; P < 0.01), aerobic and resistance training (ART) (SMD =  - 0.71; 95% CI: - 1.09 to - 0.33; P < 0.01), mind-body exercise (MBE) (SMD =  - 0.73; 95% CI: - 1.04 to - 0.43; P < 0.01), and resistance training (RT) (SMD =  - 0.66; 95% CI: - 1.02 to - 0.29; P < 0.01) all significantly improved quality of life, whereas balance and resistance training (BRT) and stretching training (ST) showed no statistically significant effects. Cumulative ranking probabilities indicated that MBE had the highest probability of being the most effective intervention (80.6%), followed by ART (76.7%), AE (70.5%), and RT (69.7%), while ST (30.7%) and BRT (18.3%) ranked lower. Dose-response analysis revealed a nonlinear U-shaped relationship between total exercise dose and improvement in quality of life, with an optimal dose of 950 MET-min/week. The optimal doses varied across exercise modalities, ranging from 550 MET-min/week for MBE to 920 MET-min/week for AE.

Conclusions: Exercise interventions can significantly improve quality of life in patients with PD, with MBE demonstrating the greatest benefit. The U-shaped association between exercise dose and quality of life suggests that a moderate amount of exercise is most conducive to improving quality of life. This study provides evidence supporting non-pharmacological treatment strategies for PD and may inform the formulation of individualized exercise prescriptions.

Background: The optimal timing of surgery for aneurysmal subarachnoid hemorrhage (aSAH) remains controversial. This study aims to identify the optimal surgical window within 72 h of symptom onset.

Methods: Patients with aSAH who underwent surgical treatment within 72 h of onset were identified from the Chinese Multicenter Cerebral Aneurysm Database (2017-2020). Multivariable Cox and logistic regression models with restricted cubic splines (RCS) were used to assess associations between onset-to-treatment time and all-cause mortality and 2-year dependent survival, respectively.

Results: A total of 3560 patients with aSAH were included. During a mean follow-up of 30.9 ± 22.5 months, 521 deaths were recorded, yielding a 2-year mortality rate of 12.9%. The RCS analysis revealed a significant U-shaped relationship between onset-to-treatment time and all-cause mortality (χ² = 5.88, df = 1, P = 0.015), as well as a significant overall association (χ² = 6.73, df = 2, P = 0.035). The lowest risk of all-cause mortality was observed at 32.6 h after onset. A monotonically decreasing association was observed between onset-to-treatment time and 2-year dependent survival (χ² = 3.70, df = 1, P = 0.055). Specifically, the risk of 2-year dependent survival declined rapidly with treatment delay during the first 12 h after onset and plateaued at approximately 32.6 h.

Conclusion: The time from onset to treatment demonstrated a nonlinear (U-shaped) association with all-cause mortality and a linear association with 2-year dependent survival, with the lowest estimated mortality risk observed at approximately 32.6 h after onset.

Early detection and monitoring of neurodegenerative processes in persons with multiple sclerosis (PwMS) is currently a major challenge. Optical coherence tomography angiography (OCTA) is an emerging method to visualize retinal vascular architecture. However, its use has mainly been investigated in relapsing MS. We evaluated OCTA as a possible complementary method in progressive MS (PMS) in a monocentric, retrospective, cross-sectional study. Eyes with evidence of optic neuritis were excluded from analysis. OCTA images acquired using a Spectralis OCT (Heidelberg Engineering) were analyzed with an established deep learning-based segmentation algorithm. After rigorous quality control, 85 eyes of 62 PwPMS were compared with 64 eyes of 43 age and gender-matched healthy controls (HC). The vessel density in the superficial vascular complex (VD_SVC (%)) was reduced in PMS compared to HC (p = 0.018). VD_SVC correlated negatively with age in PwPMS and HC. Using a Johnson-Neyman analysis, we identified that the disease duration influences the VD_SVC in PMS individuals < 57.5 years of age. PwPMS with disease duration > 10 years had reduced VD_SVC compared to subjects with ≤ 5 years of disease duration (p = 0.049) (corrected for age). Clinical disability (EDSS) negatively correlated with VD_SVC in PwPMS (β = -0.487, p = 0.010). These results suggest that OCTA might be suitable to detect retinal vascular changes in PwPMS. One consequence could be structured and harmonized OCTA investigations as part of routine clinical practice. External validation and longitudinal studies are necessary to further elaborate OCTA´s potential in monitoring PwPMS.

Objective: Our study aimed to determine the prevalence and clinical phenotypes of JAK2 pathogenic mutation carriers in the CNSR-III ischemic stroke (IS) cohort, and to develop a pre-test genetic screening model for identifying high-risk individuals.

Methods: We performed retrospective characterization of JAK2 pathogenic variants using targeted sequencing data in the CNSR-III cohort. Clinical and laboratory characteristics of JAK2 V617F mutation carriers and non-carriers were tested in a logistic regression model to identify key features. V617F screening score was developed to predict positive JAK2 V617F test results.

Results: 46 cases (0.4%, 46/10428) harbored the JAK2 V617F-exclusive mutation. Mutation carriers manifested significantly inferior functional outcomes following stroke relative to non-carriers (adjusted OR 2.74[1.07, 6.49]). Significant predictors of mutation status comprised elevated platelet count (PLT, OR 1.02[1.02, 1.03]), increased hemoglobin concentrations (HGB, OR 1.06 [1.04, 1.08]), and a reduced burden of traditional stroke risk factors, such as history of hypertension (OR 0.24[0.11, 0.52]), smoking history (OR 0.08[0.02, 0.24]), and body mass index (BMI, OR 0.8[0.75, 0.97]). We constructed the JAK2 V617F screening score, which efficiently discriminated between carriers and non-carriers (area under the ROC curve, AUC 0.98), achieving sensitivity of 85%, specificity of 94%, and accuracy of 94% for a cut-off score of 3 points. Internal validation confirmed robust performance, with a consistent AUC of 0.98.

Conclusions: Despite low prevalence (0.4%), JAK2 V617F mutation represents a clinically actionable stroke subtype with distinct pathophysiology. The prediction model offers a precision medicine approach, potentially reducing the need for comprehensive genetic testing.

Background: The hyperdense sinus sign (HDSS) is a readily identifiable non-contrast CT marker of acute thrombus in cerebral venous sinus thrombosis (CVST). We aimed to characterize HDSS associated features and prognostic significance.

Methods: Data from prospective multicenter CVST registries was analysed. HDSS was defined as attenuation > 70 Hounsfield units within a thrombosed venous structure. Baseline characteristics and outcomes were compared between patients with and without HDSS on admission CT. Multivariable logistic regression identified independent predictors of Excellent-Functional-Outcome (mRS 0-1) and remote seizures.

Results: Among 465 patients (mean age 41.9 ± 18.4 years; 64.3% female), 178 (38.3%) exhibited HDSS. Patients with HDSS had higher rates of oral contraceptives use (28% vs 18%, p = 0.009), seizures at presentation (23% vs 14%, p = 0.015), superior sagittal (45% vs 35%, p = 0.028) and transverse sinus involvement (78% vs 67%, p = 0.01), deep venous thrombosis (8% vs 2%, p = 0.003), cortical vein thrombosis (19% vs 9%, p = 0.004), and multisite occlusion (34% vs 22%, p = 0.002). Parenchymal lesions were more common in HDSS patients, including intracerebral hemorrhage (27% vs 13%, p < 0.001) and venous infarction (22% vs 11%, p = 0.004). On day-90, HDSS was associated with lower Excellent-Functional-Outcome rates (71% vs 82%, p = 0.022), higher rates of remote seizures (9% vs 3%, p = 0.001), and similar recanalization rates. HDSS independently predicted reduced odds of Excellent-Functional-Outcome (OR = 0.491 [0.261-0.926], p = 0.028) and increased remote seizures (OR = 2.693 [1.057-6.861], p = 0.038).

Conclusions: HDSS identifies a CVST subgroup with more extensive thrombosis, greater parenchymal injury, and poorer outcomes, supporting its utility in early risk stratification.

Background: Gradual worsening in relapsing-remitting MS (RRMS) may precede the formal transition to secondary progressive MS (SPMS). We aimed to quantify self-reported gradual worsening, assess concordance with clinically recorded subtype, and identify baseline predictors of discordance.

Methods: We included 1640 participants with incident RRMS from a population-based study (2005-2019). A 2021 follow-up survey captured patient-reported gradual worsening. Clinical data, including Expanded Disability Status Scale (EDSS) scores and SPMS classification, were obtained from the Swedish MS registry. Discordance with clinically recorded subtype was modeled using logistic regression stratified by subtype. Time to EDSS 3 and EDSS 4 were summarized with Kaplan-Meier estimates within subtype by self-reported worsening, and secondary Cox proportional hazards models were fitted stratified by subtype with self-reported worsening as the exposure.

Results: Among participants classified as RRMS, 24% reported gradual worsening, while 23% of those classified as SPMS did not. Kaplan-Meier curves showed clear within-subtype separation by self-reported worsening, consistent with higher hazards of reaching EDSS 3 and EDSS 4 among those reporting worsening. In RRMS, older age and higher baseline EDSS were associated with self-reported gradual worsening despite RRMS classification. In SPMS, self-reported worsening preceded clinical classification by 4.1 years.

Conclusions: Patient-reported gradual worsening aligns with disability accumulation and may help identify progression earlier than subtype reclassification, supporting integration of structured patient reports into routine monitoring.

The diagnostic approach to subjects with early-onset dementia (EOD) is often challenging due to the broader range of possible etiologies as compared to late-onset dementia cases. Pathogenic variants in CSF1R gene have been increasingly reported in subjects with EOD, mostly clinically mimicking behavioral variant of frontotemporal dementia (bvFTD). Here we screened for variants in CSF1R gene in a large cohort of dementia patients consecutively referred for genetic analysis to an Italian tertiary center between 2005 and 2024 (n = 2163). Sequence of CSF1R gene was determined with next-generation sequencing through either a dedicated panel or whole-exome sequencing. Pathogenic variants or variants of uncertain significance with higher evidence of pathogenicity were found in four participants (one female); three of these were not previously reported. Clinical data were collected, including brain magnetic resonance imaging and neuropsychological assessment. Cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) protein were measured. A family history of dementia was present in one subject. Mean age at onset was 51.5. Seizures were the presenting symptom in two cases and later appeared in other two. Two subjects presented with behavioral disturbances, resembling early bvFTD. Neuropsychological assessment revealed executive and language impairment in most cases. Anterior-predominant atrophy, symmetric white-matter involvement, and serpentine calcifications were the most common imaging abnormalities. High CSF NfL levels were found in all cases, with two of them showing markedly elevated values. CSF1R-related disease should be considered in EOD subjects, especially those presenting with executive/language deficits, seizures, white matter involvement, and markedly elevated CSF NfL levels.

Background: Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS).

Methods: We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18-39 years), transition onset (40-49 years), LOMS (50-59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions.

Results: Among 81,236 patients, 5.2% had LOMS and 1% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93).

Conclusion: LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.

Aims: Rivaroxaban has been approved for the primary prevention of stroke with non-valvular atrial fibrillation caused by one or more risk factors. However, the optimal antithrombotic therapy for secondary prevention of stroke in atrial fibrillation (AF) with ischemic stroke/transient ischemic attack (TIA) had been uncertain. We compared the safety and efficacy of novel oral anticoagulants. (NOACs) and Warfarin in treating AF with ischemic stroke.

Methods: Seven databases were searched from inception up to December 2024 for studies comparing NOACs and Warfarin in AF with ischemic stroke. 7 randomized controlled trials (RCTs) and 9 cohort studies with 128,808 patients were included. A random-effects model or fix effects model was used.

Results: Pooled results showed that the NOACs are superior to Warfarin in the prevention of stroke or systemic embolism (RR 0.90, 95%CI [0.82,1.0], P = 0.04) and all-cause mortality (RR 0.83, 95%CI [0.76,0.92], P = 0.0003). As well as NOACs has lower risk in total bleeding (RR 0.79, 95%CI [0.76,0.83], P < 0.00001), fatal bleeding (RR0.64, 95% CI [0.54,0.76], P < 0.00001), hemorrhagic stroke (RR0.50, 95%CI [0.43,0.58], P < 0.00001), and intracranial bleeding (RR 0.49, 95%CI [0.36,0.65], P < 0.00001) than Warfarin.

Conclusion: In the secondary prevention with AF related to ischemic stroke, NOACs showed potential advantages over Warfarin in the incidence of stroke or systemic embolism, all-cause mortality, total bleeding, fatal bleeding, hemorrhagic stroke, and intracranial bleeding.