Journal of Neurology最新文献

Huntington's disease (HD) remains a devastating neurodegenerative disorder caused by CAG repeat expansion in the HTT gene. Biomarkers are urgently needed to facilitate more accurate evaluation of disease onset, progression, and response to interventions. Characteristic clinical features of the disease are secondary to neuronal dysfunction, and the eye provides a potential window to characterize these changes. In this review, we systematically evaluate clinical studies examining ocular abnormalities in HD, including oculomotor function and retinal anatomy assessed by optical coherence tomography. Findings indicate that while ocular abnormalities can be identified in HD, their clinical utility remains unclear. Further evaluation in large cohorts of gene-positive individuals followed longitudinally is required.

Parkinson's disease (PD) is the second most common neurodegenerative disease and the fastest-growing disability-causing neurological disorder worldwide. Based on the CPDR cohort from 19 clinical centers, we summarized the mortality information and characteristics of patients with PD, and analyzed the related factors affecting their survival. After a 6-year follow-up period, 562 of the 3,148 patients died, with a mortality rate of 3.03 deaths per 100 person-years, and a median survival time from disease onset of 23.33 years. The most common cause of death was cardiovascular disease, followed by cerebrovascular disease and respiratory disease. Older age at onset, carriers of GBA1 gene variants, type 2 diabetes, higher LEDD, late H&Y stage (especially H&Y stage 4 and H&Y stage 5), higher UPDRS part Ⅲ scores, a history of falls, depression, and cognitive dysfunction were associated with increased mortality. In contrast, undergoing deep brain stimulation (DBS) surgery and higher educational attainment was associated with a lower risk of death. Our findings contributed to further expanding the survival data of PD and advocated for early identification of high-risk patients for timely intervention to improve prognosis.

Background: Neuropathological examinations in spinocerebellar ataxia type 3 (SCA3) have demonstrated peripheral and autonomic nervous system degeneration, but the impact of associated symptoms on genetically affected individuals at different disease stages remains understudied.

Objective: To investigate the clinical burden of peripheral and autonomic nervous system involvement in SCA3 mutation carriers across the disease spectrum.

Methods: Forty SCA3 mutation carriers, including ten pre-ataxic individuals, completed questionnaires about muscle cramps, neuropathic pain, autonomic symptoms, activities of daily living, and quality of life, and underwent a standardized clinical examination of ataxia and neuropathy severity. Data were compared with 16 healthy controls.

Results: All but one of the ataxic and 60% of pre-ataxic individuals experienced muscle cramps at least weekly. Neuropathic pain was reported by 20% of pre-ataxic and 16.7% of ataxic mutation carriers, while the average number of autonomic symptoms in both groups was 2 and 4.7, respectively. Neuropathy severity scores were significantly higher in pre-ataxic and ataxic individuals than in healthy controls and associated with (i) worse self-reported functional status and (ii) clinician-reported ataxia severity. The number of autonomic symptoms was associated with patient-reported impairments in daily life and quality of life.

Conclusion: Clinical features of peripheral and autonomic nervous system degeneration are very common in SCA3, may already be observed in pre-ataxic individuals, and independently contribute to patient-reported disease burden and clinician-rated overall ataxia severity.

Fatigue is prevalent in the general population, but it is unclear whether aging is associated with increased fatigue. Here, we investigate the relationship between cognitive fatigue (CF, fatigue resulting from mental work) and two types of aging-chronological age and brain age-in 85 participants ranging in age from 20 to 84 years. Whereas chronological age is simply participants' absolute age, brain age is derived from a comparison of participants' brain morphology relative to a normative model. CF was induced using a working memory paradigm that participants repeatedly performed, reporting their instantaneous level of CF at baseline and after each successive block of the task. Chronological age was associated with a decrease in the CF reported at baseline (the intercept of a regression line fit to the CF ratings), whereas brain age was related to the rate at which fatigue was induced (the slope of the regression line fit to the CF ratings). Behaviorally, the decrease in CF as a function of chronological age was mirrored by a more liberal response bias, providing more evidence that response bias represents an objective behavioral index of CF. Additionally, areas of the insula showed a relationship between CF and chronological age, suggesting that the role of the insula may change across the lifespan. These results represent the first well-powered study to investigate the relationship between CF and chronological age as well as brain age and suggests that CF may be an important indicator of brain age across the lifespan.

Objective: To evaluate the feasibility, safety, and preliminary efficacy of a novel single-lead, dual-target deep brain stimulation (DBS) approach targeting the posterior subthalamic area (PSA) and subthalamic nucleus (STN) for dystonic tremor.

Methods: This retrospective pilot study reviewed outcomes of six consecutive patients with medically refractory dystonic tremor who underwent single-lead PSA-STN DBS at our center (June-December 2024). Clinical outcomes were assessed using the BFMDRS and FTMTRS scales. A formal blinded crossover assessment was performed in three patients to compare PSA-only, STN-only, and combined stimulation. Chronic settings were selected via patient-directed optimization.

Results: All six patients completed follow-up (100% retention) and achieved stable chronic stimulation programs. Five patients (83.3%) independently selected combined PSA + STN stimulation; one preferred STN-only. At LFU (6-12 months postoperatively), the mean BFMDRS-Motor score decreased by 78.1% and FTMTRS by 87.1%. The crossover assessment (n = 3) showed that combined stimulation outperformed single-target stimulation. No serious adverse events occurred. All efficacy analyses are exploratory.

Conclusion: This single-lead, dual-target PSA-STN DBS approach demonstrates feasibility and preliminary efficacy for dystonic tremor. Prospective controlled trials are warranted.

Background: Data on cognition in adult patients with myelin oligodendrocyte glycoprotein antibody-associated disease (pwMOGAD) are scarce.

Objective: To examine cognitive function in pwMOGAD and assess relative risks (RR) for cognitive impairment (CImp) in pwMOGAD relative to healthy controls (HC), aquaporin 4-immunoglobulin G positive neuromyelitis optica spectrum disorders (pwAQP4+NMOSD), and double-seronegative NMOSD (pwdsNMOSD) compared to HC.

Methods: Data derived from a cohort with neuroimmunological disorders. Cognitive performance was assessed using Rao's brief repeatable battery of neuropsychological tests, compared to HC using confounder-adjusted linear regressions. CImp was defined as performing two standard deviations below the HC mean in any subtest. RR for CImp was calculated using generalized linear models.

Results: We evaluated cognitive performance of 21 pwMOGAD and 25 HC. CImp was additionally determined in 43 pwAQP4+NMOSD and 15 pwdsNMOSD. PwMOGAD performed worse on Selective Reminding Test, and the symbol digit modalities test compared to HC. Adjusted RR for CImp were 1.9 (95% CI 0.9-4.1) in pwMOGAD, 1.9 (95% CI 1.0-3.9) in pwAQP4+NMOSD and 2.1 (95% CI 0.9-4.6) in pwdsNMOSD.

Conclusion: pwMOGAD performed worse in information processing speed, verbal learning, storage and retrieval compared to HC. RR for CImp in pwMOGAD compared to HC was similar to that estimated for pwAQP4+NMOSD and pwdsNMOSD.

Background: Spinal cord injuries and disorders (SCI/D) have been reported by some studies to correlate with increased risk of ischemic cerebral stroke. However, the reports are sparse, conflicting, generally lacked SCI/D-specific analysis, and commonly had small sample sizes.

Objective: To determine whether SCI/D are a risk factor for ischemic stroke and evaluate for underlying SCI/D-related stroke risk correlations.

Methods: Using a retrospective design aimed to capture a large sample with SCI/D, first-ever stroke incidence was estimated by Poisson regression models for US Veterans with and without SCI/D during fiscal years 2017-2021 using US Veterans Health Administration and Medicare utilization data. Models were adjusted for Veteran characteristics, common stroke risk factors, and prescriptions for stroke-prophylactic medications.

Results: Analyses included 560,314 Veterans, including 12,450 with SCI/D. Adjusting for person-days, age, sex, smoking, diabetes, hypertension, atrial fibrillation, race, ethnicity, and stroke-prophylactic medications, Veterans with SCI/D had a 19% higher stroke incidence compared to controls [incidence rate ratio (IRR) 1.19, 95%CI: 1.11-1.28]. Compared to controls, stroke incidence was 50% and 31% higher with high and low tetraplegia, respectively [IRR 1.50, 95%CI: 1.17-1.92 and IRR 1.31, 95%CI: 1.02-1.67], and markedly higher for younger Veterans with SCI/D (ages < 40 years) [IRR 2.25, 95%CI: 1.24-4.08]. Relative to controls, stroke incidence was 36% higher with non-traumatic SCI/D [IRR 1.36, 95%CI: 1.24-1.49], but not with traumatic spinal cord injury [IRR 1.05, 95%CI: 0.95-1.17].

Conclusion: SCI/D are a risk factor for ischemic stroke in US Veterans, especially for Veterans with tetraplegia, non-traumatic SCI/D, and younger age.

Background: Early reperfusion (ER) following intravenous thrombolysis improves outcomes in large vessel occlusion stroke (LVOS). Tenecteplase (TNK) has been associated with higher ER rates than alteplase (TPA), but findings across studies remain inconsistent, possibly due to limited adjustment for thrombus burden, characteristics, and collateral status. We compared TNK and TPA in a real-world cohort incorporating imaging-based assessment of thrombus and collateral status.

Methods: We retrospectively analyzed consecutive anterior circulation LVOS patients who received intravenous thrombolysis prior to thrombectomy at two U.S. comprehensive stroke centers (2020-2024). ER was defined as eTICI ≥ 2b50 on initial angiography or confirmed recanalization in clinically improving patients who did not undergo thrombectomy. Imaging review included clot burden score, thrombus length, thrombus permeability, and collateral status (Tan scale). Multivariable logistic regression identified predictors of ER. Ordinal logistic regression assessed the association between ER and 90-day modified Rankin Scale (mRS) shift.

Results: Among 299 patients (TNK 201, TPA 98), ER occurred in 60 (20.1%). ER was more frequent with TNK than TPA (24.4% vs 11.2%, p = 0.008). TNK was independently associated with ER (adjusted OR 2.54, 95% CI 1.19-5.42). Additional predictors included thrombus permeability (aOR 3.30, 95% CI 1.73-6.30) and lower NIHSS (aOR 0.94 per point, 95% CI 0.89-0.98), while tandem occlusion reduced ER likelihood (aOR 0.18, 95% CI 0.05-0.62). ER independently predicted better 90-day mRS (aOR 2.09, 95% CI 1.21-3.60).

Conclusions: Tenecteplase achieved superior early reperfusion compared to alteplase after accounting for clot burden, thrombus features, and collateral status, reinforcing its clinical advantage in LVOS thrombolysis.