Journal of Neurology最新文献

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.

Background and aims: Guillain-Barré Syndrome (GBS) refers to a group of acute inflammatory polyradiculopathies characterized by a diffuse inflammatory attack on the peripheral nervous system, often triggered by a preceding infection. Despite significant progress in both diagnosis and treatment, only a few prognostic systems and useful biomarker have been proposed. In this study, we propose galectin-3 (Gal-3), a novel serum molecule identified expressed by Schwann cells and macrophages, as a potential biomarker with both prognostic and diagnostic significance in patients with GBS.

Methods: Serum levels of Gal-3 and neurofilament light chain (NfL) were measured using the Simple Plex cartridge-based immunoassay on the Ella platform (ProteinSimple, San Jose, CA, USA) in serum samples from a cohort of patients with GBS (n = 19) and in a validation cohort of healthy control subjects (n = 13). We also collected data on clinical history and patient outcomes to assess the potential utility of Gal-3 as a diagnostic and predictive biomarker.

Results: Gal-3 levels were significantly higher in patients with GBS (median: 7041 pg/mL; IQR: 5576-8561) compared to healthy controls (median: 5030 pg/mL; IQR: 3877-5998; p < 0.05). Within the GBS cohort, Gal-3 levels were significantly elevated in patients with the axonal variant compared to those with the acute inflammatory demyelinating polyneuropathy (AIDP) variant (median: 8561 pg/mL vs. median: 5998 pg/mL, p < 0.05). A positive correlation was observed between serum Gal-3 levels and NfL levels (ρ = 0.47; p < 0.05). In multivariate logistic regression, log-transformed Gal-3 remained significantly associated with the axonal variant of GBS after adjustment for age at sampling, presence of diarrhea, GBS Disability Score at admission, and log-transformed NfL (β = 3.5, OR = 33, p = 0.048). In ROC curve analysis, Gal-3 demonstrated good discriminatory performance between axonal GBS and AIDP (AUC = 0.84), outperforming NfL (AUC = 0.76). Gal-3 threshold of 6457.5 pg/mL was identified, yielding 100% sensitivity and 61.5% specificity for distinguishing axonal GBS, whereas an NfL threshold of 177.5 pg/mL achieved 83% sensitivity and 84% specificity.

Conclusion: In our cohort, Gal-3 was associated with both diagnostic and prognostic features in patients with GBS. These findings suggest that Gal-3 may serve as a potential biomarker for differentiating axonal subtypes within the GBS spectrum. However, further in vitro and in vivo studies are required to elucidate the cellular source and pathophysiological role of Gal-3 in acute inflammatory polyneuropathies, as well as to evaluate its feasibility and clinical applicability as a biomarker in GBS.

Objective: To investigate the differences in clinical characteristics, laboratory parameters, and radiological findings between patients with complete and incomplete recovery of isolated abducens nerve palsy (IANP).

Methods: We retrospectively analyzed 107 patients diagnosed with IANP from 3 centers. Individuals with other cranial nerve involvement or neurological deficits were excluded. Data on demographics, clinical features, laboratory results, and imaging findings were collected and analyzed.

Results: Among 107 patients, 66 achieved complete recovery, while 41 had incomplete recovery. Analysis of clinical characteristics showed that the distribution pattern of the side of palsy (left, right, or bilateral, P = 0.018), etiology (P = 0.019) and preceding infection (P = 0.044) were significantly correlated with poor outcomes. Analysis laboratory results revealed that higher erythropoietin (EPO) levels were also significant associated with incomplete recovery (OR = 1.126, 95% CI 1.026-1.236, P = 0.013), while imaging findings and cerebrospinal fluid (CSF) parameters showed no significant association with recovery outcomes. Multivariate analysis identified four factors were associated with incomplete recovery: preceding infection (OR = 8.690, 95% CI 1.219-61.946, P = 0.031), trauma history (OR = 13.389, 95% CI 1.257-142.604, P = 0.032), time of symptom onset (OR = 1.033, 95% CI 1.002-1.064, P = 0.035), and EPO levels (OR = 1.139, 95% CI 1.035-1.253, P = 0.008).

Conclusions: Preceding infection, trauma history, time of symptom onset, and EPO levels were identified as predictors of incomplete recovery in IANP patients, while imaging findings and CSF parameters showed no significant association with recovery outcomes. These findings provide new clinical insights by guiding prognostic assessment (e.g., preceding infection history and monitoring EPO levels) and highlighting modifiable (e.g., prompt medical intervention) and non-modifiable (e.g., trauma history) factors that personalized management strategies for IANP patients.