Frontiers in Neurology最新文献

Background: Migraine is a leading cause of disability worldwide, yet national-level epidemiological data are often lacking, hindering public health planning. This study aimed to provide the first comprehensive, population-based assessment of migraine epidemiology, comorbidity burden, and preventive treatment patterns in Israel.

Methods: We conducted a retrospective cohort study using electronic health records from Clalit Health Services (CHS), which insures over 50% of the Israeli population. 4,614,331 adults were included in the analysis. Patients with migraine were identified between 2000 and 2023 using physician-recorded ICD-9 codes or dispensed triptan prescription. Patients with migraine were matched 1:2 with non-migraine controls to assess comorbidities. We calculated point prevalence, annual incidence, and analyzed the preventive treatment landscape before and after the introduction of calcitonin gene related peptide (CGRP)-related migraine-specific preventive treatments.

Results: The study included 356,441 patients with migraine and 4,257,890 controls. Migraine disproportionately affected females (75.8%) and younger adults (mean age 30.7 ± 13.2 years). Observed prevalence was lower than global estimates across most age strata. Incidence peaked among women aged 18-24 at 7.5 cases per 1,000 individuals. Patients with migraine carried a substantial comorbidity burden compared with age- and sex-matched controls. The highest adjusted odds ratios (ORs) were observed for chronic pain and psychiatric diseases (ORs for low back pain 2.67, fibromyalgia 2.42, endometriosis 1.86, anxiety 2.02, and depression 1.81). Vascular and metabolic conditions (hypertension, dyslipidemia, atrial fibrillation, and cerebrovascular disease) were more frequent, and stroke risk was significantly elevated. A negative association was found with diabetes. The proportion of patients who used preventive medication was low (9.6 and 8.8%, in 2018 and 2022 respectively) and did not increase after the introduction of migraine-specific treatments. Preventive use was most common in young adults (18-24 age group) and middle-aged adults (45-54 age group).

Conclusion: This large national population-based study reveals a high comorbidity burden among patients with migraine and suggests significant underdiagnosis compared to global benchmarks. The use of preventive treatment remained strikingly low, including novel migraine-specific therapies. These findings underscore the need for improved migraine recognition, integrated multidisciplinary care, and policy-level strategies to reduce the burden of this disabling condition.

Introduction: Mild traumatic brain injury (mTBI) is a heterogeneous condition with long-term sequelae, yet diagnosis in the chronic stage remains limited by reliance on acute criteria and subjective reports. Objective biomarkers are needed, as current blood-based markers show diagnostic value primarily in the acute and subacute phases. Resting-state EEG (RS-EEG) can capture large-scale network disruptions through functional connectivity (FC) and microstate analysis, but its role in chronic mTBI is unclear.

Methods: We tested whether RS-EEG features distinguish chronic mTBI from controls and predict symptom burden. This observational case-control study included 44 participants (18 chronic mTBI, 26 controls). Source-reconstructed EEG was analyzed for spectral power, microstate metrics, and FC using the Multivariate Interaction Measure (MIM). Elastic Net and XGBoost models classified injury status and predicted symptom severity, with feature robustness evaluated across full and reduced electrode montages.

Results: Participants with mTBI showed no group differences in spectral power or microstate metrics but demonstrated significantly elevated FC across theta, beta, gamma, and broadband frequencies. Connectivity increases were stable across reduced montages and persisted up to 8 years post-injury. Classification models using MIM achieved AUCs of 0.79-0.89 for injury status and 0.82-0.87 for symptom severity, outperforming demographic models. Resting-state EEG FC provides a sensitive biomarker of chronic mTBI, distinguishing cases from controls and correlating with symptom severity.

Discussion: The persistence of network alterations years after injury suggests lasting changes in brain activity associated with chronic symptom burden. These findings support the use of RS-EEG-derived FC as a noninvasive and scalable biomarker of chronic mTBI.

Heat therapy (HT) has been shown to improve peripheral blood glucose regulation in some populations, yet its effects on brain glucose metabolism remain largely unexplored. The chronic benefits of HT may arise in part from upregulation of heat-shock proteins (HSPs). These proteins play a crucial role in the stress response and modulate diverse processes such as proteostasis and cell signaling pathways, including that of insulin signaling. Understanding the impact of HT on both peripheral and central glucose metabolism, including the effects of varying temperatures, is essential for elucidating potential mechanisms underlying its brain benefits. The Feasibility of Improving Glycemia to prevent Alzheimer's Disease (FIGHT-AD) study is a randomized controlled trial that aims to investigate changes in blood and brain glucose regulation following 10 weeks of HT. Specifically, we will examine the peripheral biomarker responses to warm and hot HT and assess how these responses relate to brain metabolic changes in both treatment groups. This trial will be the first to quantify the effect of HT on cerebral glucose metabolism in individuals at metabolic risk for Alzheimer's Disease (AD). The FIGHT-AD trial will provide critical data to inform the design of future clinical trials targeting metabolic and brain health through HT.

Clinical trial registration: clinicaltrials.gov, identifier NCT06023407.

Background: Intracranial and/or extracranial atherosclerotic stenosis is a common etiology of acute ischemic stroke (AIS). This study aimed to evaluate the impact of intracranial or extracranial atherosclerotic stenosis on early neurological deterioration (END), hemorrhagic transformation (HT) and 90-day clinical outcomes in patients receiving intravenous thrombolysis.

Methods: We retrospectively enrolled patients with AIS who received intravenous alteplase (0.9 mg/kg) at the First Affiliated Hospital of Kunming Medical University between February 2019 and August 2022. Data on demographics, stroke risk factors, laboratory results, and neuroimaging findings were collected. Atherosclerotic stenosis (AS) was defined as >50% intracranial or extracranial arteries. Logistic regression was performed to identify independent predictors of clinical outcomes. END was defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale (NIHSS) score within 24 h after stroke onset. HT was defined as any newly detected intracranial hemorrhage on follow-up cranial CT performed within 7 days after symptom onset.

Results: A total of 185 AIS patients receiving intravenous thrombolysis were included in this study, with 88 (47.6%) in the IEAS group and 97 (52.4%) in the non-stenosis group. There was no significant association between the incidence of END and the presence of IEAS. Multivariable regression analysis revealed that baseline NIHSS was an independent risk factor for HT (OR = 1.120, 95% CI 1.038-1.209, p = 0.003), 90-day poor clinical outcome (OR = 1.198, 95% CI 1.105-1.298, p = 0.001) and 90-day death (OR = 1.384, 95% CI 1.179-1.625, p = 0.001). Although IEAS was not significantly associated with the incidence of END or HT, it was significantly correlated with 90-day poor clinical outcome (OR = 1.350, 95% CI 1.108-1.644, p = 0.003).

Conclusions: In this cohort, IEAS was not associated with END or HT but emerged as an independent predictor of poor 90-day functional outcome after intravenous thrombolysis for AIS.

Background: The expression of p53 protein is closely related to tumor prognosis and plays an important role in patients with pituitary neuroendocrine tumors (PitNETs). However, its evaluation currently relies on postoperative histopathological analysis. Developing a non-invasive method to predict p53 overexpression preoperatively may help support clinical judgment and facilitate individualized treatment strategies.

Methods: Clinical and imaging data from 186 patients with pathologically confirmed PitNETs were retrospectively collected. The cohort was divided into training and testing sets using stratified random sampling. Radiomic features were extracted from MRI sequences, and feature selection was performed using the intraclass correlation coefficient (ICC) and least absolute shrinkage and selection operator (LASSO). A radiomics score was calculated, and univariate and multivariate logistic regression analyses were used to identify independent clinical risk factors. A combined nomogram model incorporating clinical and radiomic features was constructed. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), precision-recall (PR) curve, calibration curve, and decision curve analysis (DCA).

Results: Four radiomic features and two clinical features were selected for model development. Age (odds ratio [OR] = 0.97, 95% confidence interval [CI]: 0.94-0.99, p = 0.01) and suprasellar invasion (OR = 0.47, 95% CI: 0.25-0.89, p = 0.02) were identified as independent predictors of p53 positivity. The combined clinical-radiomic model achieved good predictive performance with an AUC of 0.77 in the validation set, demonstrating favorable discrimination, calibration, and clinical utility.

Conclusion: The proposed MRI-based radiomics model, integrating clinical and imaging features, enables non-invasive preoperative prediction of p53 overexpression in PitNETs. This approach offers a promising tool for individualized risk stratification and personalized treatment planning in neurosurgical practice.

Background: While the significance of inflammation in Parkinson's disease (PD) pathogenesis has been established, the relevance of emerging hematological markers such as the systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) to this disorder requires further investigation.

Methods: Whole blood were collected and analysed for the measured parameters from 222 Parkinson's disease (PD) patients and 298 healthy controls (HCs), All PD patients undergoing comprehensive neuropsychological assessment. Partial correlation analysis was used to evaluate the correlation between SII, SIRI and PD severity, after adjusting for age. Logistic regression models were constructed to evaluate the associations of these inflammatory indices with PD risk, while receiver operating characteristic (ROC) analysis assessed their diagnostic performance.

Results: The SII and SIRI were substantially higher in patients with PD than in HCs. Both the SII and SIRI were positively correlated with Hoehn and Yahr staging scale (H&Y), Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS-I, UPDRS-II, and UPDRS-III scores. Conversely, the SII exhibited a negative relationship with Mini-Mental State Examination (MMSE) scores. A binary logistic regression model demonstrated that the SII [odds ratio (OR), 1.601; 95% confidence interval (CI) 1.484-1.828, p < 0.001] and SIRI (OR, 1.487; 95% CI, 1.319-1.609, p < 0.001) were independent factors for PD. The area under the curve (AUC) values for the SII, SIRI, and SII & SIRI for PD were 0.750, 0.700, and 0.785, respectively.

Conclusion: Our findings support the potential utility of elevated SII and SIRI as biomarkers for assessing PD severity.

Traumatic brain injury (TBI) unfolds through a well-defined chronology-hyperacute excitotoxic and inflammasome bursts, acute apoptotic and blood-brain-barrier failure, and subacute neurovascular remodeling-that no single-pathway drug can adequately cover. Recombinant erythropoietin (EPO) limits secondary damage in animals, yet its erythropoietic drive and thrombotic liability have stalled clinical adoption. This review integrates structural biology, pharmacology and translational data on four engineered EPO derivatives-carbamylated EPO, asialo-EPO, darbepoetin alfa and the helix-B surface peptide (HBSP/cibinetide)-that decouple cytoprotection from red-cell stimulation. We first outline how specific modifications (carbamylation, desialylation, hyper-glycosylation or helix truncation) bias EPOR signaling toward PI3K-AKT and away from JAK2-STAT5. We then match each derivative to its optimal injury window. Meta-analyses of randomized trials suggest a possible trend toward lower short-term mortality without a consistent functional benefit or thrombotic signal. By integrating molecular mechanisms, experimental findings, and early clinical observations, this review outlines hypotheses and future trial frameworks for phase-targeted, erythropoietin-based neuroprotection. Further controlled studies are required to establish safety, efficacy, and optimal therapeutic timing before translation to routine clinical use.

Gaucher disease 2 (GD2) is a rare and rapidly progressive neuropathic lysosomal storage disorder with an average survival of 11-19 months. To date, no approved therapy is available, but the variant-dependent pharmacological chaperone ambroxol (ABX) has emerged as a promising off-label therapy. This long-term observational study encompasses 2 GD2 patients treated with high-dose ABX from the age of 4 and 1 months, respectively, in addition to enzyme replacement therapy (ERT). Previously published data of patient 1 demonstrated a significant increase in β-glucocerebrosidase activity in ABX-treated patient fibroblasts alongside nearly age-appropriate neurocognitive and motor development after 3 years of ABX therapy. Follow-up assessments at the present age of 6.5 years continued to show normal neurocognitive development. Glucosylsphingosine (Lyso-GL1) levels in cerebrospinal fluid (CSF) remained significantly decreased compared to pre-treatment levels. In patient 2, ABX-treated fibroblasts exhibited a slight increase in β-glucocerebrosidase activity. Nevertheless, Lyso-GL1 levels in CSF showed a notable decrease compared to baseline. Neurocognitive and motor function assessments at 40 months of age indicated a moderate to severe developmental delay, yet continuous developmental progress. These interim findings contribute to the mounting evidence supporting ABX as a variant-dependent treatment for GD2 patients.

Background: Perimenopausal women frequently experience insomnia and negative emotions due to hormonal fluctuations. Acupuncture, a traditional Chinese therapy, has attracted significant interest for its potential to regulate endocrine function and alleviate insomnia. Despite this, no systematic review has hitherto evaluated the efficacy of acupuncture on insomnia and negative emotions in perimenopausal women. This network meta-analysis was conducted to assess the therapeutic effects of acupuncture on these conditions, thereby generating robust clinical evidence to inform evidence-based practice and guide future research directions.

Methods: A systematic literature search was performed in multiple databases, such as PubMed, Web of Science, Medline, Scopus, Wanfang, CNKI, VIP Database, and CBM, covering all records from inception through November 2025. The primary outcome was measured using the Pittsburgh Sleep Quality Index (PSQI), while secondary outcomes were evaluated through various depression and anxiety scales, including the Kupperman Menopausal Index, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Beck Depression Inventory, and Beck Anxiety Inventory.

Results: According to the network meta-analysis, the top three interventions identified for the improvement of PSQI scores were, in order: routine acupuncture combined with auricular acupuncture; auricular acupuncture combined with Western medicine; and routine acupuncture combined with Pentatonic therapy. Seven interventions demonstrated significant effects compared to SH (P < 0.05). Regarding negative moods, balance acupuncture combined with Xiaoyao powder, routine acupuncture combined with pentatonic therapy, and abdominal acupuncture combined with sedative prescription and western medicine ranked highest (P < 0.05).

Conclusion: This network meta-analysis suggests that routine acupuncture combined with auricular acupuncture may be an effective intervention treatment for treating insomnia in perimenopausal women. Furthermore, balanced acupuncture combined with Xiaoyao powder may have a positive effect in alleviating negative emotions.

Background: Mild non-disabling ischemic stroke (MNDIS) is increasingly treated with intravenous thrombolysis, yet a substantial proportion of patients still experience poor functional outcomes, and robust tools for individualized risk prediction are lacking.

Methods: In this retrospective cohort study, we analyzed 713 consecutive MNDIS patients who received intravenous thrombolysis within 4.5 h of symptom onset at an advanced stroke center between January 1, 2022 and December 31, 2024. Poor outcome was defined as a 90-day modified Rankin Scale (mRS) score ≥2. Candidate predictors, including demographic, clinical, laboratory, hemodynamic and imaging variables, were first screened by univariable analysis and then entered into a stepwise multivariable logistic regression model (entry p < 0.05, removal p > 0.10). A nomogram incorporating independent predictors was constructed in R, and its performance was evaluated using receiver operating characteristic (ROC) analysis, bootstrap calibration, and decision curve analysis.

Results: Of the 713 patients, 91 (12.8%) had poor 90-day outcomes (mRS 2-6) and 622 (87.2%) had good outcomes (mRS 0-1). Admission NIHSS score (OR 1.37; 95% CI 1.10-1.72), 24-h NIHSS score (OR 1.78; 95% CI 1.52-2.10), diastolic blood pressure (OR 1.02 per mmHg; 95% CI 1.00-1.05), and coronary heart disease (OR 1.88; 95% CI 1.05-3.35) were independently associated with poor outcome. The resulting nomogram showed good discrimination (AUC 0.835; 95% CI 0.805-0.861; sensitivity 71.4%; specificity 84.1%), excellent calibration (bootstrap mean absolute error 0.014), and provided positive net clinical benefit across a wide range of risk thresholds (0.03-0.89).

Conclusion: Admission and 24-h NIHSS scores, diastolic blood pressure, and coronary heart disease are key predictors of poor 90-day outcomes after thrombolysis in patients with MNDIS. The derived nomogram offers accurate, well-calibrated, and clinically useful individualized risk estimation, and may assist clinicians in early post-thrombolysis risk stratification and tailoring the intensity of monitoring and follow-up.