Journal of Neurology最新文献

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.

Background: Nusinersen and risdiplam are approved disease-modifying therapies for adults with 5q-associated spinal muscular atrophy (SMA). To date, no direct comparison of the two treatments in adults has been conducted. Real-world cohorts of nusinersen and risdiplam differ in key baseline characteristics, such as motor function and disease severity, making direct comparison challenging. Nevertheless, such analyses are important for treatment decisions.

Methods: We conducted a single-center, prospective, matched-pair analysis of adult persons with SMA (pwSMA) treated with nusinersen or risdiplam between 2017 and 2025. Patients were matched 1:1 based on baseline motor scores (Hammersmith Functional Motor Scale-Expanded [HFMSE], Revised Upper Limb Module [RULM]) and adjusted for age and disease duration at treatment initiation. Motor function was assessed at baseline, 4-8, 10-14, 22-26, and 32-40 months after treatment initiation. Pairwise difference scores (Δ-values) were analyzed using non-parametric tests.

Results: From a cohort of 101 pwSMA (65 nusinersen, 36 risdiplam), 24 matched pairs (n = 48) were identified. Baseline demographic and clinical characteristics did not differ between groups. Over a maximum follow-up of nearly three years, no differences were observed in the trajectories of HFMSE or RULM scores between the nusinersen and risdiplam group. Within each group, motor function remained stable without significant decline.

Conclusions: In this first matched-pair comparison of nusinersen and risdiplam in adults with SMA, both treatments achieved similar stabilization of motor function over almost three years. Larger, multicenter studies are warranted to confirm these results and explore potential subgroup-specific treatment effects.

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic condition associated with an elevated risk of cognitive impairment, particularly in domains of executive function and attention, presenting a pattern distinct from Alzheimer's disease. This review synthesizes evidence from multimodal neuroimaging studies to characterize the cerebral alterations in COPD and frame them within the context of accelerated brain aging. Patients with COPD exhibit widespread structural brain changes, including reduced gray matter volume in cognitively critical regions, such as prefrontal cortex, cingulate gyrus, hippocampus, and basal ganglia. Concurrently, white matter damage is evident as microstructural abnormalities in tracts including the cingulum bundle and corona radiata, alongside white matter hyperintensities. These microstructural abnormalities are characterized by decreased fractional anisotropy and increased mean diffusivity. Furthermore, neurovascular uncoupling, indicated by an imbalanced ratio of cerebral blood flow to degree centrality in frontal-temporal areas, contributes to network inefficiency. These neuroimaging abnormalities are closely associated with deficits in executive function, attention, and visuospatial abilities. The underlying pathophysiology involves synergistic effects of systemic hypoxia, chronic inflammation, and neurovascular-coupling dysfunction, which collectively promote a cascade of brain injury resembling accelerated aging. Elucidating this unique neuropathological profile not only enhances the understanding of COPD-related cognitive decline but also highlights potential shared mechanisms with broader brain aging processes, offering insights for early diagnosis and targeted intervention strategies.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder for which current pharmacological treatments, while initially effective, often lead to long-term motor fluctuations and complications. Transcranial pulse stimulation (TPS) is a novel non-invasive neuromodulation technique that uses mechanical stimuli through shockwaves to induce neuroplasticity.

Methods: This open-label, single-arm pilot study enrolled 14 individuals with PD who received 12 TPS sessions over 4 weeks. Stimulation targeted motor and symptom-specific cortical regions. Outcomes were assessed across motor, non-motor domains, and EEG at baseline, after 3, 6, 9, and 12 sessions, and at 1-month follow-up.

Results: TPS produced significant and consistent improvements across different domains. After 12 TPS sessions, UPDRS total scores improved by 9.43 points (p < 0.001, Cohen's d = - 0.566), and UPDRS Part III improved by 4.93 points (p < 0.001, d = - 0.498). Non-motor symptom burden was reduced by 19.14 points (p = 0.014, d = - 0.754). Cognitive performance improved substantially, with a 7.28-point gain on the SCOPA-COG (p < 0.001, d = 1.161). Quality of life improved by 1.30 points on the PDQ-39 SI (p = 0.005, d = - 0.690), and depression symptoms by 3.43 points on the BDI-II (p = 0.008, d = - 0.644). Follow-up analyses demonstrated that all clinical effects were sustained one month after treatment.

Conclusion: TPS appears to induce clinically meaningful and lasting improvements across multiple domains in PD, accompanied by EEG changes that indicate enhanced neuroplasticity. However, due to the nature of this pilot open-label trial, these results should be interpreted as preliminary, hypothesis-generating findings that require confirmation in adequately sham-controlled randomized clinical trials.

Objectives: This study aimed to investigate four plasma markers, pTau231, sTREM2, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP), in relation to disease severity in a Korean cohort of progressive supranuclear palsy (PSP).

Methods: Baseline data from patients with probable PSP enrolled in the SCANPSP cohort (NCT05579301) were compared with those of age-matched healthy controls (HC). Four plasma markers measured using the Simoa method, clinical findings, and volumetric 3 T MRI were investigated.

Results: This study included 68 patients with PSP and 30 HC. Group level difference were found in NFL, correlating with the PSP-rating scale (r = 0.48, p = 2.0·10^-4) and global cognitive scores (r = -0.34, p = 0.0061 for Mini-Mental Status Exam: r = -0.32, p = 0.0088 for Montreal Cognitive Assessment). Intercorrelations between NFL, pTau231, and GFAP were observed in patients with PSP but no intercorrelations in HC. The combination of pTau231, NFL, and GFAP yielded the highest ability to distinguish the PSP-Richarson syndrome (PSP-RS) from the PSP-subcortical, with an area under the curve of 0.80. The gray matter voxel-wise correlation of whole patient data showed that NFL correlated with third ventricle enlargement and frontal/cingulate atrophy, whereas sTREM2 correlated with third ventricle and thalamic volumes. White matter analyses revealed that the supplementary motor area and vermis correlated with NFL in whole PSP. In PSP-RS group, the superior frontal gyrus was associated with NFL, and the cerebellar crus with sTREM2.

Conclusion: This study demonstrated the feasibility of using four plasma markers simultaneously to determine PSP disease severity. To verify these findings, longitudinal analyses are necessary.

Plasma phosphorylated-tau (p-tau) biomarkers show high performance as first-in-line tests in the evaluation of patients with cognitive symptoms and have also found utility in clinical trials for anti-amyloid drug therapies for Alzheimer's disease (AD). Plasma p-tau212 is a novel blood biomarker that can discriminate cognitively unimpaired (CU) and subjective cognitive decline patients from mild cognitive impairment (MCI)-AD and AD dementia patients in clinical cohorts. Using Simoa technology, we evaluated plasma p-tau212 for its ability to detect emerging amyloid-beta (Aβ) pathology in CU individuals with brain amyloidosis from CSF Aβ42/40 ratio (n = 317) or Aβ PET scans (n = 277). We benchmarked plasma p-tau212 against p-tau181, p-tau217, and p-tau231 by comparing their accuracies and fold changes for detecting brain amyloidosis. Our results showed that all the plasma p-tau biomarkers are increased in the CU CSF Aβ + participants, with the highest median fold change observed for plasma p-tau212. Discrimination performance of the biomarkers to differentiate amyloid PET-positive from amyloid PET-negative participants differed between plasma p-tau biomarkers, being higher for plasma p-tau217 and p-tau212 compared to plasma p-tau181 and p-tau231. Furthermore, plasma p-tau212 was elevated in participants with low Aβ burden (CSF Aβ-positive, amyloid PET-negative), supporting its potential as a cost-effective, easily implemented biomarker for trial recruitment in early stages. Its further increase in Aβ PET-positive participants suggests additional utility for monitoring anti-amyloid therapies.

Multiple system atrophy (MSA) is an adult onset progressive, sporadic neurodegenerative disorder. Individuals with MSA display a range of symptoms, including autonomic dysfunction, Parkinsonian features, and cerebellar impairment. Although symptomatic treatments can improve patients' quality of life, their effects are often temporary and do not alter disease progression or address its pathogenic causes. MSA patients undergo a prodromal phase that precedes the gradual onset of neuropathological changes. Therefore, understanding the early pathological events is essential for unraveling the disease's mechanisms and developing therapies to slow down its progression. Over the past five years, significant progress has been made in understanding the pathogenesis of MSA. Key findings in the epidemiology and genetics of the disease have highlighted a central role of α-synuclein (α-Syn) in the development of MSA. Numerous preclinical and clinical studies highlighted novel aspects of α-Syn aggregation, neuroinflammation, neurotrophic support, and mitochondrial dysfunction. This review covers both the traditional understanding and recent developments in MSA pathogenesis and provides an overview of related clinical trials, offering insights for future research directions in MSA.

Background: Highly effective disease-modifying therapies (HEDMTs) for relapsing multiple sclerosis (RMS) have changed the landscape of MS treatment. However, their discontinuation may potentially result in recrudescence of the disease activity. We aimed to investigate the effectiveness of Rituximab (RTX) in RMS patients who discontinued HEDMTs because of efficacy or safety reasons.

Methods: This observational study analyzed data of RMS patients treated with RTX who discontinued natalizumab [NTZ]; fingolimod [FTY], alemtuzumab [ALM], cladribine [CLD], cyclophosphamide [CYC], and mitoxantrone [MIT]), followed by the MS centers contributing to the Italian Multiple Sclerosis and Related Disorders Register. Disability progression (progression independent from relapse activity [PIRA] and from MRI activity [PIRMA]) and disease activity (annualized relapse rate [ARR], relapse-associated worsening [RAW]) were compared at pre-baseline (last evaluation during HEDMTs), at baseline (at the time of RTX initiation; ± 3 months), at 12 ± 3 (T12), and at 24 ± 3 months (T24) after RTX initiation.

Results: Out of 68,621 RMS patients, 599 were treated with RTX. Of them, 362 (119 [67.6%] females, mean age of 44.2 ± 11.6 years) were finally enrolled. A total of 176 (48.6%) patients were previously treated with NTZ, 160 (44.2%) with FTY, 11 (3%) with ALM, 10 (2.8%) with CLD and 5 (1.4%) with CYC-MIT. After RTX initiation, in the NTZ, and CYC-MIT groups, disability outcomes remained stable over the time. In the FTY, ALM and CLD groups, RAW, PIRA, and PIRMA significantly reduced after 2 years of treatment with RTX. Cox analysis showed that higher EDSS before starting HEDMTs and at pre-baseline were associated to higher risk of PIRA, while factors predicting higher risk of PIRMA were older age at RTX initiation and EDSS before starting HEDMTs.

Discussion: RTX potentially represents a rescue therapy for those patients requiring the discontinuation of highly active drugs and more vulnerable to relapse or disease progression.