Journal of Neurology最新文献

Introduction: Optical coherence tomography (OCT) can detect neuroaxonal loss in multiple sclerosis (MS) patients, with thinning of the ganglion cell layer (GCL) reflecting neurodegeneration. Ofatumumab (OMB), a subcutaneous anti-CD20 monoclonal antibody, has demonstrated efficacy against inflammatory activity, though its neuroprotective potential is less established. This study aimed to assess longitudinal OCT changes in MS patients treated with OMB compared to those receiving non-anti-CD20 disease-modifying treatments (DMTs).

Methods: This longitudinal observational study included relapsing-remitting MS patients initiating Ofatumumab, with OCT and EDSS assessments at baseline and 24 months, compared with a retrospective control group on non-anti-CD20 DMTs. Eyes with prior optic neuritis were excluded. Longitudinal GCL thickness was analyzed using a nested linear mixed-effects model, including random intercepts for patients and eyes nested within patients and multivariate linear regression adjusting for baseline characteristics.

Results: We analyzed 85 eyes from 47 patients (OMB: 46 eyes; control: 39 eyes). Baseline GCL was lower in OMB patients, who also had longer disease duration and higher EDSS. Over 24 months, GCL remained stable in OMB patients (+ 0.28 µm/year; p = 0.06), while controls showed significant thinning (- 0.99 µm/year; p < 0.001). In the adjusted multivariate regression model including age, sex, baseline GCL, EDSS, and disease duration, treatment with OMB was independently associated with reduced GCL loss (β = 2.41 µm/year, 95% CI 1.38-3.43, p < 0.001).

Conclusions: OMB treatment was associated with significant retinal preservation, independent of baseline differences and confounders. These results suggest a potential neuroprotective effect of B-cell depletion in MS and support the utility of OCT as a sensitive biomarker for treatment monitoring.

Background: Amnestic mild cognitive impairment (aMCI) represents a prodromal stage of Alzheimer's disease and carries a high risk of progression to dementia. Disruptions in functional brain networks, synaptic degeneration, and tau pathology each serve as neural markers of cognitive decline in aMCI. In this study, we employed a multimodal neuroimaging approach to determine whether integrating these markers provides a more powerful explanation of cognitive deterioration than examining them individually.

Methods: Twenty-eight aMCI patients and 24 healthy controls underwent cognitive assessment, resting-state fMRI, ¹¹C-UCB-J PET (synaptic density), and ¹⁸F-MK-6240 PET (tau). Eighteen aMCI patients were reassessed after 2 years. Graph-theoretical measures of network topology were derived, and linear regression models were used to examine whether combining functional, synaptic, and tau markers improved prediction of cognitive decline in aMCI.

Results: Longitudinal changes in right hippocampal characteristic path length, synaptic density, and tau accumulation jointly predicted decline in delayed memory recall, achieving a higher predictive performance (adjusted R² = 0.753) than unimodal models (adjusted R² range: - 0.009-0.421), with reduced overfitting degree.

Conclusions: Multimodal neuroimaging integrating functional network topology, synaptic density, and tau burden improves prediction of memory decline in aMCI. These findings highlight complementary neural processes underlying progression and support multimodal imaging as a valuable approach for monitoring in prodromal Alzheimer's disease.

Mutations in the superoxide dismutase 1 (SOD1) gene are a predominant, genetic cause of amyotrophic lateral sclerosis (ALS). Given the marked variability in SOD1 variant prevalence and clinical manifestations across global populations, this study aimed to characterize the genetic and clinical profile of SOD1-associated ALS (SOD1-ALS) in a large cohort of Indian patients. Whole-exome sequencing (WES) was performed for the retrospective cohort, along with comprehensive bioinformatic analyses and interpretation of genetic variants. Data were analyzed using descriptive statistics and Kaplan-Meier survival analysis to assess clinical and survival outcomes. Among 765 individuals who underwent WES, 37 probands (4.8%) from 33 families were identified with SOD1-ALS, representing a substantial 24.2% of familial ALS (fALS) cases. Patients showed a male preponderance (1.64:1) with a mean age at onset of 41.9 ± 13.1 years. Analysis revealed 23 distinct pathogenic/likely pathogenic SOD1 variants, including four novel variants. Remarkably, a high frequency of homozygous variants (6 patients) were observed in the cohort, which were associated with earlier disease onset. Most patients presented with a lower limb onset (67.6%) and a lower motor neuron phenotype. Survival was noted to be prolonged in carriers of H47R, V88M, and I152N variants, while those with juvenile onset showed reduced survival. In conclusion, this study provides the first comprehensive characterization of SOD1-ALS in the Indian population, revealing a distinct genetic profile with a unique spectrum of SOD1 variants and a higher prevalence of homozygous cases. These detailed genotype-phenotype correlations contribute significantly to the genetic etiology of ALS.

Background: Continuous EEG (cEEG) monitoring is critical for detecting seizures in hospitalized patients, but optimal durations of EEG monitoring remain unclear, particularly after a seizure has been detected on monitoring.

Methods: We conducted survival analysis on 117 patients with electrographic or electroclinical seizures who underwent cEEG at the University of Wisconsin Hospital (UWH) between 2018 and 2022. Time from the end of seizure-to-seizure recurrence or cEEG termination was analyzed using Cox regression.

Results: In univariate analysis, status epilepticus (SE) was the only clinical feature significantly associated with increased risk of seizure recurrence (P = 0.022). The estimated EEG duration required to reduce seizure recurrence risk below 5% was 36.8 h in patients with SE and 21.2 h in those without SE. Numerous other clinical variables, including coma, antiseizure medications addition, use of anesthetic infusions, history of epilepsy, and epileptiform discharges, were not significant.

Conclusion: Our findings support current clinical practices of at least 24 h of EEG monitoring following seizure cessation and highlight that patients with a history of status epilepticus may require longer monitoring. These data reinforce the value of individualized, risk-based approaches to EEG monitoring strategies.

Background: Deep brain stimulation (DBS) is an effective treatment for motor symptoms in Parkinson's disease (PD). However, its effects on non-motor symptoms (NMS) have been rarely assessed due to inconsistencies in evaluation methods used in different studies. This meta-analysis aimed to assess the effects of DBS on NMS in PD using studies that employed consistent, standardized evaluation tools.

Methods: A systematic review was conducted following the PRISMA guidelines. Longitudinal studies published between 2007 and 2024 were included if they evaluated bilateral DBS using identical NMS scales with involvement of at least six studies per tool. Assessment tools included the Beck Depression Inventory (BDI and BDI-II), the Hamilton Depression Rating Scale (HAMD), the Apathy Evaluation Scale (AES), the Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), the Non-Motor Symptoms Scale (NMSS), the Mini-Mental State Examination (MMSE), and the Parkinson's Disease Questionnaire-39 (PDQ-39).

Results: Notably, 57 studies involving 3,200 patients were included. DBS significantly improved NMS, including depression (SMD:-0.19 to -0.35), sleep quality (PDSS SMD: 0.68; ESS SMD: - 0.32), and overall NMS (SMD: - 0.62). Moreover, quality-of-life was significantly improved (SMD: - 0.71), except in the communication domain. Although the levodopa equivalent daily dose (LEDD) was reduced by 49.2%, no significant correlation was found between LEDD reduction and quality-of-life improvement.

Conclusion: DBS could provide significant improvements in key NMS of PD, independent of reductions in LEDD. These findings revealed the direct neuromodulatory effects of DBS and highlighted its role in personalized treatment planning, particularly for patients with prominent depressive symptoms or sleep disturbances.

Eculizumab as C5 complement protein inhibitor has been approved for the maintenance treatment of neuromyelitis optica spectrum disorder (NMOSD). However, evidence regarding its efficacy in the acute phase remain limited. This study enrolled six patients with aquaporin-4 (AQP4)-IgG-seropositive neuromyelitis optica, including five cases of optic neuritis and one case of long-segment transverse myelitis. These patients exhibited no or partial symptomatic improvement following glucocorticoid pulse therapy, and two patient experienced further deterioration. Subsequently, eculizumab was added to the treatment regimen, and all patients achieved rapid symptom improvement without adverse events reported post-infusion. The addition of eculizumab to glucocorticoid therapy during the acute phase may significantly ameliorate symptoms in AQP4-IgG-positive NMOSD patients with rapid onset of action and favorable safety profile. This may provide a new treatment option for patients with poor response to glucocorticoids in the acute phase, while mitigating glucocorticoid-related adverse effects to a certain degree.

Objective: To evaluate the real-world effectiveness and safety of eculizumab in patients with AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) and to identify predictors of disability outcomes.

Methods: This multinational, retrospective cohort study analyzed data from 46 patients across 26 centers. The outcomes included the annualized relapse rate (ARR), relapse-free status, change in expanded disability status scale (EDSS) scores, and adverse events. To identify predictors of EDSS improvement or worsening, patients were stratified into subgroups (improved vs. stable/worsened) at each follow-up time point and compared based on demographic, clinical, and radiological variables.

Results: This retrospective cohort study included 46 patients with AQP4-IgG-positive NMOSD from 26 centers, followed for a mean of 27.3 months. The mean ARR significantly decreased from 1.1 in the 2 years pre-treatment to 0.1 during eculizumab therapy. The relapse-free rate increased from 6.5% pre-treatment to 80.4%. Mean EDSS scores improved from 4.2 at baseline to 3.6 at 24 months. The presence of area postrema syndrome was associated with a favorable prognosis, while the presence of spinal attacks was associated with a poor prognosis at 12 months. Adverse events occurred in 7 patients (18.9%), leading to permanent discontinuation in only two.

Conclusion: Eculizumab demonstrated robust real-world effectiveness in reducing relapse rates and stabilizing disability, with an acceptable safety profile. Clinical outcomes may be influenced by attack phenotype, underscoring the importance of early intervention.

Introduction: Patients undergoing radiotherapy for cancer usually have several other comorbidities and are taking various medications. Both of these factors can affect the individual radiation sensitivity of normal tissue. We therefore studied persons with epilepsy (PWE) to determine whether they had altered radiation sensitivity.

Material and methods: Blood samples were collected from 105 adult patients with epilepsy and compared to those of healthy individuals and oncological patients. The samples were irradiated ex vivo and analyzed by 3-color fluorescence in situ hybridization. In each patient, aberrations were analyzed in 200 metaphases of chromosomes 1, 2, and 4 and scored as breaks. Radiosensitivity was determined by mean breaks per metaphase (B/M) and compared to both healthy donors and oncologic patients.

Results: Radiosensitivity (B/M) of the PWE (n = 105, B/M: 0.478) was clearly increased compared to healthy individuals (n = 209, B/M: 0.420) and oncological patients (rectal patients and breast cancer patients, n = 319, B/M = 0.442). Antiseizure medications tended to increase radiation sensitivity. The use of perampanel (0.505 B/M; p = 0.081) and lacosamide (0.521 B/M; p = 0.014) led to a clear increase in radiation sensitivity. Male PWE (0.502B/M, p = 0.004) were distinctly radiosensitive which may be potentially explained by the fact that women were recommended to take high doses of folic acid according to German guidelines at the time of the study. Factors like seizure frequency, epilepsy duration, polytherapy and comedication did not contribute to increased radiosensitivity.

Conclusion: PWE were clearly increased radiosensitive compared to healthy individuals and oncological patients. Male PWEs were found to be more sensitive than female PWEs. This may be due to their higher intake of folic acid, a substance which can protect against radiation.

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.