Frontiers in Neurology最新文献

Epilepsy is a frequent complication observed among stroke survivors. Post-stroke epilepsy (PSE) is defined as the occurrence of at least two unprovoked seizures beyond 2 weeks of an acute stroke that are not due to any other identifiable cause. PSE constitutes a significant clinical concern in pediatric stroke patients, adversely affecting both short-term and long-term management outcomes. This systematic review aimed to identify patient-related, stroke-related, and seizure-related risk factors associated with the development of PSE in the pediatric population. We included all clinical studies that compared these variables between pediatric stroke patients who developed PSE and those who did not. Studies reporting potential predictors of PSE among children with stroke were incorporated into the analysis. A total of 16 studies comprising 3,198 patients were included. The pooled risk of PSE was 27.6%, with a 95% confidence interval ranging from 19.8 to 37.2% (p < 0.001). Statistically significant associations were observed between younger age at stroke onset (OR 0.838; 95% CI 0.796-0.883; p < 0.001), cortical involvement (OR 3.151; 95% CI 1.132-8.772; p = 0.028), middle cerebral artery involvement (OR 3.541; 95% CI 1.068-11.738; p = 0.039), and increased risk of PSE. Additionally, patients presenting with acute symptomatic seizures (HR 3.924; 95% CI 2.580-5.967; p < 0.001) and those experiencing prolonged acute symptomatic seizures (OR 4.7; 95% CI 2.286-9.662; p < 0.001) demonstrated a higher likelihood of developing PSE. Pediatric patients who are younger at stroke onset and exhibit cortical or middle cerebral artery involvement are at a substantially elevated risk for PSE. Furthermore, the presence of acute symptomatic seizures at stroke onset, particularly when prolonged, markedly increases the probability of subsequent PSE development.

CRISPR-Cas genome-editing technologies have emerged as powerful tools for precise DNA and RNA modulation, offering promising therapeutic strategies for neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This review critically evaluates current CRISPR/Cas applications in neurodegeneration, with emphasis on mechanistic insights, therapeutic outcomes, and translational feasibility. Preclinical and early translational studies demonstrate that CRISPR-Cas platforms can correct pathogenic mutations, suppress toxic gene expression, and restore neuronal function. Advanced modalities, including base and prime editing, CRISPRi/a, and RNA-targeting Cas systems, improve precision and reduce genomic damage, which is particularly advantageous in post-mitotic neurons. Emerging CRISPR-based diagnostics (e.g., SHERLOCK and DETECTR), AI-assisted sgRNA design, and machine-learning approaches for predicting off-target effects further enhance the safety, stratification, and monitoring of CRISPR therapeutics. In parallel, patient-derived brain organoids and assembloids provide scalable human-relevant platforms for mechanistic studies and preclinical validation. Despite this progress, major challenges remain, including efficient delivery across the blood-brain barrier, immune responses, long-term safety, and ethical and regulatory considerations. Overall, CRISPR-Cas technologies hold strong potential as disease-modifying interventions for neurodegenerative disorders, provided that advances in delivery systems, artificial intelligence integration, and regulatory oversight continue to evolve toward clinical translation.

Objective: This study aims to assess changes in the cross-sectional area of the tibial nerve in the disabled elderly.

Materials and methods: The study sample included 124 tibial nerves in 62 participants; 16 of which were disabled elderly patients (13 males, 3 females), with a mean age of 66.6, a mean height of 167.1 cm, a mean weight of 83.9 kg, and a mean BMI of 29.9. Twenty-three young controls (6 males, 17 females), a mean age of 48.4, a mean height of 154.9 cm, a mean weight of 79.8 kg, a mean BMI of 32.7, and 23 elderly non-disabled participants (13 males, 10 females), a mean age of 63.6, a mean height of 161.9 cm, a mean weight of 80.56 kg, and a mean BMI of 30.88.

Results: The mean CSA of the TN in the elderly disabled group was 28.5 mm². The mean CSA of the young control group's TN was 20.45 mm². The mean CSA of the TN in the elderly non-disabled group (both diabetic and non-diabetic) was 27.6 mm². The mean CSA of the TN in the elderly diabetic non-disabled group was 29.9 mm². The mean CSA of the TN in the elderly (non-diabetic) non-disabled group was 24.6 mm².

Conclusion: In conclusion, although our study suggests that nerve ultrasound could be a helpful tool for assessment of the tibial nerve in disabled elderly patients, disability status was not an independent predictor of tibial nerve CSA. Future studies with a larger sample size and a homogenous group are suggested.

Objective: The objective of the study was to evaluate the safety and efficacy of ocrelizumab (OCR) and rituximab (RTX) in multiple sclerosis.

Methods: This was a retrospective single-centre study. Ocrelizumab- and rituximab-treated patients were identified through the multiple sclerosis (MS) registry maintained at Aga Khan University Hospital Nairobi (AKUHN), Kenya. Adult patients aged 18-65 years old who fulfilled the McDonald 2017 diagnosis criteria and received treatment with either rituximab or ocrelizumab between January 2016 and June 2025 were retrospectively evaluated. Data collected at baseline included age, gender, first symptoms, disease duration since onset, MS phenotype, treatment duration, previous therapies, reasons for switching to anti-CD 20 (cluster of differentiation) therapy, date of start of anti-CD 20 therapy, and adverse events. Disease activity was evaluated both clinically and through magnetic resonance imaging (MRI).

Results: A total of 67 patients (male:female, 14:53) received anti-CD 20 therapy, with the majority having relapsing-remitting MS (RRMS) (5277.6%), while the rest had progressive MS. Patients were treated with either ocrelizumab 600 mg or rituximab 1,000 mg administered intravenously (IV) every 6 months. After 1 year, the cumulative relapse rate dropped, with the number of patients having clinical relapse events reduced from 48 to 7. Overall, 40 patients had stable MRI findings, 7 had new MRI lesions, and 20 did not have follow-up scans. No infusion-related adverse events or life-threatening infections were reported with the administration of anti-CD 20 therapy, and no case of malignancy or progressive multifocal encephalopathy was detected.

Conclusion: This retrospective, single-centre study provides real-world data on B-cell-depleting therapies in an African MS cohort. Ocrelizumab and rituximab appear to be safe, well-tolerated, and effective therapeutic options for people living with MS.

Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Mobilization is defined as the application of assisted movement and physical therapy to hospitalized patients, including progressive exercise and ambulation programs. While early mobilization in the intensive care unit (ICU) has been shown to be a safe and effective intervention to improve patient outcomes in the general ICU cohort, there is currently limited evidence specific to patients with acute TBI. The aim of this service evaluation was to identify current mobilization activity and functional outcomes in patients admitted to the ICU at our institution following an acute TBI.

Methods: A single-center retrospective service evaluation was performed for all patients, over 16 years-old, admitted to the ICU at our institution (a Level 1 major trauma center) with an acute TBI between January 2022 and November 2024. Patient demographics, ICU admission details, TBI severity (based on the Glasgow Coma Scale [GCS]) and functional outcomes were extracted. Mobilization outcomes included the timing of the commencement of mobilization (defined as sitting on the edge of the bed or better) and mobilization status, defined using the Manchester Mobility Scale (MMS).

Results: The service evaluation included 353 patients, of whom 56.0% had severe TBI (GCS: 3-7). Mobilization was achieved in ICU for 53.0% of patients, with a further 18.1% first mobilized on a hospital ward post-ICU discharge. The first mobilization occurred at a median of 11 days (interquartile range: 6-18) after ICU admission. In patients surviving to ICU discharge, 28.9% had an MMS of 1 (bed-based exercises) at this time, with only 9.1% achieving an MMS of 7 (mobilizing 30 meters or more). Analysis by TBI severity found a significant decline in in-hospital mobilization rates with increasing TBI severity (90.7% vs. 58.4% for mild vs. severe TBI; p < 0.001), with a corresponding increase in the time to the first mobilization (median: 6 vs. 13 days for mild vs. severe TBI; p < 0.001).

Conclusion: Acute TBI patients admitted to the ICU at our institution had low rates of mobilization and achieved low levels of mobility at ICU discharge. This service evaluation highlights the need for prospective studies into early mobilization practices in the neurotrauma ICU.

Introduction: Traumatic brain injury (TBI) and epilepsy are significant health concerns among the veteran population, but the links between mild TBI and cognitive and behavioral changes in epilepsy have been little explored. This study leveraged natural language processing of medical records and chart review to assess the prevalence and patterns of cognitive and behavioral symptoms in post-9/11 veterans with epilepsy, with and without history of mild TBI. The study objective was to identify distinct neurobehavioral phenotypes, and then explore their socio-demographic factors, comorbidities, and phenotypes.

Methods: We conducted a detailed chart review using NLP to extract cognitive dysfunction indicators that were categorized into seven Research Domain Criteria domains. Employing Uniform Manifold Approximation and Projection for clustering and dimensionality reduction.

Results: By clustering individuals on behavioral and cognitive concepts in medical notes, this study extends beyond traditional diagnostic classifications, revealing a cognitive and behavioral phenotype of veterans. Veterans with post traumatic epilepsy often demonstrate significant cognitive risk profiles associated with RDoC domains, particularly in domains related to cognitive function and arousal/regulatory systems. Both veterans with TBI before Epilepsy post traumatic epilepsy and those with epilepsy preceding TBI displayed greater cognitive and behavioral burden compared to veteran with TBI only. Notably, epilepsy preceding TBI were found more often clustering in high behavioral risk profiles. This group with epilepsy preceding TBI was associated with, including dysfunction in the RDoC domains related to negative valence systems (44.4%), arousal/regulatory systems (37.0%), and interpersonal trauma.

Discussion: These findings highlight the complex interplay between TBI and Epilepsy in shaping long term cognitive/behavioral challenges and point to the need for targeted clinical management, personalized treatment approaches, and refined therapeutic strategies to maximize the quality of life for affected veterans.

Microembolic signals (MES) detected by transcranial Doppler (TCD) provide real-time information on ongoing embolic activity in patients with ischemic stroke and transient ischemic attack. MES have been associated with stroke recurrence and high-risk conditions including large-artery atherosclerosis, atrial fibrillation, moyamoya disease, cancer-related stroke, and complex aortic arch plaques. Despite its clinical value, conventional TCD is limited by operator dependency, suboptimal acoustic windows, and limited ability to discriminate embolus characteristics. Recent advances in artificial intelligence (AI), including machine learning algorithms and robotic-assisted TCD systems, offer automated and reproducible MES detection, improved artifact rejection, and advanced signal interpretation. This mini-review summarizes the clinical relevance of MES, the main limitations of conventional TCD, and current and emerging applications of AI to MES detection, highlighting future perspectives for stroke risk stratification and personalized secondary prevention.

Background: Sepsis-associated encephalopathy (SAE), a devastating complication of sepsis, lacks specific biomarkers and clear pathophysiological understanding, particularly regarding the gut-brain axis. While gut dysbiosis is implicated in SAE, the underlying mechanisms remain elusive.

Methods: This study employed an integrated multiomics approach (16S rDNA and fecal miRNA sequencing) to dissect the gut microenvironment in SAE patients (n = 10) compared to sepsis patients without encephalopathy (SP, n = 20).

Results: Although α- and β-diversity indices showed no significant differences, distinct compositional shifts in the gut microbiota were observed in SAE patients, characterized by increased abundance of Neisseria, Haemophilus, Lautropia, Enterococcus, Parabacteroides, and decreased Fusobacterium, Phocaeicola, Bacteroides, among others. Concurrently, 12 fecal miRNAs were differentially expressed (DE) in SAE, with 11 upregulated (e.g., miR-106a-5p, miR-181a-5p, miR-223-5p, miR-30e-3p) and 1 downregulated (miR-222-3p). Crucially, correlation network analysis revealed significant interactions between 10 DE miRNAs and 15 bacterial genera, establishing a complex gut microbiota-miRNA interplay in SAE. Machine learning (LASSO and elastic net regression) identified miR-30e-3p and miR-223-5p as the most promising combined diagnostic biomarkers, achieving an area under the curve (AUC) of 0.893. Functional exploration via ceRNA network analysis indicated miR-30e-3p targets inflammation and apoptosis-related genes (e.g., IL1B, RPS6KB1, AKT1), while miR-223-5p primarily targets immune-regulatory genes (e.g., IGF1, AR). Experimental validation confirmed significantly elevated serum IL-1β levels in SAE patients (p < 0.001), supporting the predicted inflammatory pathway.

Conclusion: This study provides the first evidence of a fecal miRNA-gut microbiota interaction network in SAE pathogenesis, highlighting miR-30e-3p and miR-223-5p as pivotal mediators and potential diagnostic/therapeutic targets.

Objective: This study aimed to assess the utility of lumbar lamina and ligamentum flavum boundaries as anatomical landmarks for the precise localization and resection of lumbar intraspinal schwannomas using a minimally invasive tubular approach.

Methods: We conducted a retrospective analysis of 17 patients who underwent surgical resection between September 2021 and September 2023. Preoperative imaging was used to determine the optimal lamina landmarks relative to the tumor's poles or midpoint. The boundaries or specific sites of the ligamentum flavum subsequently guided the precise drilling of the bone window. We recorded intraoperative parameters, including retractor inclination angle, operative time, and blood loss. Patient outcomes were assessed during a two-year follow-up using the Oswestry Disability Index (ODI), MRI to evaluate resection, and X-ray to assess spinal stability.

Results: All tumors were successfully resected without neurological complications. The mean operative time was 119.7 ± 14.7 min, mean blood loss was 47.1 ± 11.9 mL, and the mean retractor angle was 6.3 ± 2.5°. After a mean follow-up of 30.9 ± 1.6 months, ODI scores showed significant improvement, decreasing from 31.5 ± 5.4% to 14.9 ± 3.4%. Postoperative MRI confirmed gross-total resection in all cases, and X-rays revealed no spinal instability.

Conclusion: The boundaries of the lumbar lamina and ligamentum flavum are reliable and effective anatomical landmarks. Utilizing these landmarks facilitates precise, minimally invasive resection and is correlated with favorable short-term outcomes.