Annals of Neurology最新文献

Objective: The objective of this study was to compare clinical features and prognosis of late-onset neuromyelitis optica spectrum disorder (LO-NMOSD, onset age ≥60 years) with adult-onset NMOSD (AO-NMOSD, onset age 18-59 years), and to provide insights for individualized management in elderly patients.

Methods: Data from 748 patients with NMOSD (diagnosed according to the 2015 International Panel for NMO Diagnosis criteria) in the China National Registry of Neuro-Inflammatory Diseases (CNRID) were analyzed. Patients were stratified into AO-NMOSD (18-59 years, n = 617) and LO-NMOSD (≥ 60 years, n = 131). Demographics, clinical manifestations, imaging, treatments, and outcomes were compared using appropriate statistical methods including Kaplan-Meier survival curves and Cox proportional hazards regression.

Results: LO-NMOSD showed distinct traits: a lower female predominance (76.34% vs 86.55%), higher transverse myelitis (TM) incidence at onset (57.36% vs 40.17%), elevated annualized relapse rate (ARR; 0.52 ± 0.03 vs 0.38 ± 0.01), and accelerated disability (median Expanded Disability Status Scale [EDSS] 4.75 vs 3.0). TM-predominant relapses (39 of 45, 86.67% in LO vs 96 of 148, 64.86% in AO) contributed significantly to disability. Kaplan-Meier analysis showed LO-NMOSD had a higher risk of relapse (hazard ratio [HR] = 1.932, 95% confidence interval [CI] = 1.427-2.615), disability (HR = 3.192, 95% CI = 1.932-5.274) and reaching visual acuity (VA) ≤20 of 30 (HR = 3.523, 95% CI = 1.585-7.828). Cox regression confirmed that onset age ≥60 years was an independent risk factor for relapse (HR = 2.05, 95% CI = 1.60-2.59), disability (HR = 3.16, 95% CI = 2.14-4.62), and reaching VA ≤20 of 30 (HR 3.26, 95% CI = 1.83-5.48).

Interpretation: LO-NMOSD is characterized by myelitis-predominance with recurrent spinal cord involvement, high risk of relapses, and severe disability. It thus underscores the need for heightened clinical attention, with rigorous monitoring that balance safety and efficacy for elderly patients with NMOSD. ANN NEUROL 2026.

Objective: Carpal tunnel syndrome (CTS) can drastically impair one's ability to work and interferes with activities of daily living. We recently demonstrated that, in rodents, conditioning electrical stimulation (CES) delivered to the nerve 7 days prior to surgery imparts a conditioning lesion-like effect by accelerating the rate of regeneration along the entire length of the nerve. The goal of this study is to test the hypothesis that CES could accelerate nerve regeneration and improve function in patients with moderate or severe CTS.

Methods: Using a double-blind randomized controlled study design, patients received surgery + CES or surgery + sham stimulation. They were evaluated at regular intervals for 12 months following intervention. Primary outcome was motor unit number estimation (MUNE), supplemented with secondary outcomes including motor and sensory nerve conduction studies, Semmes Weinstein Monofilaments, and Moberg Pick-Up Test.

Results: Sixty-four participants were randomized to either the treatment or control groups. There was no significant demographic or physiological difference at baseline between the groups. No major adverse event was found with treatment. Following intervention, there was significantly greater increase in MUNE of 62 ± 71 in the treatment group compared to 25 ± 66 in the controls after 12 months. In the treatment group, there was correspondingly better physiological and functional recovery and hand dexterity compared with the controls.

Interpretation: CES is a safe, feasible, and efficacious treatment to improve nerve reinnervation and functional outcomes in patients with moderate or severe CTS. This may open future possibilities for more effective treatment for other peripheral nerve injuries. ANN NEUROL 2026.

Objective: Cervical artery dissection (CeAD) may be limited to the extracranial extradural space or extend to the intradural space. Intradural extension can potentially increase the risk of stroke and subarachnoid hemorrhage. However, the factors associated with intradural extension and its impact on clinical outcome remain unclear.

Methods: This was a secondary analysis of the STOP-CAD observational, multi-center study. Patients with CeAD and intradural extension (CeADid) were compared with those with pure CeAD extradural dissections (CeADed) using multiple regression analyses.

Results: Of 4,023 patients with CeAD, 534 (13.3%) had CeADid. In comparison to patients with CeADed, those with CeADid more often had clinical overt stroke or transient ischemic attack (TIA) at presentation, acute infarcts on imaging, a vertebral artery affected, and severe stenosis of the involved vessel (p < 0.001 for all). In contrast, carotid involvement and complete occlusions were more frequent in patients with CeADed (p < 0.001 for both). CeADid was associated with a shift in the distribution of scores on the modified Rankin Scale (mRS) toward worse functional outcome (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.62-0.92) but the odds for favorable outcomes (mRS = 0-2) did not differ between the groups after appropriate adjustments on multivariate analysis. CeADid was independently associated with higher mortality at 180 days on multivariate analysis (adjusted OR = 2.84, 95% CI = 1.50-5.38).

Interpretation: CeADid is associated with more severe clinical presentation, a shift toward less favorable outcomes, and higher mortality rates. These findings suggest that CeADid may represent a high-risk type of CeAD. ANN NEUROL 2026.

Objective: The evidence regarding adherence to dietary patterns and Parkinson's disease (PD) risk is inconsistent. Because of the long prodromal PD phase, reverse causation represents a major threat to investigations of diet in relation to PD. We examined whether adherence to the Mediterranean (MED) and Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diets is associated with PD incidence, while considering reverse causation, in a large cohort of women with a 25-year follow-up.

Methods: Participants from the E3N (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale) study were prospectively followed-up from 1993 to 2018. PD diagnoses were validated using medical records and drug claim databases. Baseline MED and MIND scores were computed using a validated food questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression models. Exposures were lagged by 5 years in main analyses and longer lags in sensitivity analyses. We performed age-stratified analyses and adjusted for prodromal symptoms.

Results: Analyses (5-year-lag) are based on 71,542 women (845 PD patients). Higher adherence to MED and MIND diets was not associated with PD overall, but was associated with lower PD incidence in women <71 years old (MED, HR_{high vs. low+medium} = 0.76 [0.58-1.00], p-Age × MED interaction = 0.038; MIND, HR_{high vs. low+medium} = 0.75 [0.58-0.97], p-Age × MIND interaction = 0.035). Legumes and high unsaturated to saturated fat ratio had the strongest contribution for the MED diet, while beans and olive oil had the strongest contribution for the MIND diet. Results were consistent after adjustment for constipation/depression and in analyses with lags up to 20 years.

Interpretation: Adherence to the MED and MIND diets was associated with lower PD incidence <71 years in women. These findings are important for planning preventative interventions. ANN NEUROL 2026.

Objective: The objective of this study was to determine whether missing individual doses of anti-seizure medications (ASMs) elevate short-term seizure risk in people with drug-resistant epilepsy.

Methods: In a prospective, community-based cohort, adults with drug-resistant epilepsy (≥ 3 seizures/month) or their caregivers recorded seizures and ASM intake with smartphone applications for 10 months each. Individual level analysis modeled the relationships between ASM adherence with seizure occurrence, as well as with a simplified seizure forecast via a 90-day moving average ("Napkin method"). Group-level analysis with a mixed-effects model was performed to examine the relationship between ASM adherence and simplified forecasts, while controlling for differences in individual seizure frequency via random effects.

Results: Twenty-seven participants (median age = 29 years) contributed 7,853 person-days. Individual analysis showed that only a small (n = 2) number of participants had a weak relationship between ASM adherence with seizure occurrence. Group-level analysis showed that seizure occurrence was highly linked to the Napkin method, but not ASM adherence.

Interpretation: Among individuals with frequent, drug-resistant epilepsy, occasional missed ASM doses did not measurably raise immediate seizure risk. Whereas sustained nonadherence remains a clinical concern, clinicians may reassure patients that infrequent brief lapses are unlikely to trigger seizures acutely, yet they should continue emphasizing overall adherence for long-term seizure control. ANN NEUROL 2026.

The risk allele rs10191329*A is associated with disease severity and brain atrophy in people with multiple sclerosis (MS). We investigated the association of rs10191329 with age-related brain atrophy in a population-based cohort using 10,308 magnetic resonance imaging (MRI) scans of 4,815 participants aged ≥ 45 years without MS in cross-sectional and longitudinal analyses. We observed associations between the rs10191329*A allele and lower total brain volume and gray matter volume in middle-aged (< 55 years of age), but not in older participants. These data suggest that rs10191329*A contributes to earlier onset of atrophy in the general population, and that mediating mechanisms of accelerated neurodegeneration extend beyond MS. ANN NEUROL 2026.