Frontiers in Neurology最新文献

Objective: This study aimed to develop and validate a predictive model that integrates audiological and psychometric variables to individually predict responses to sound therapy in tinnitus patients.

Methods: This study included 342 patients with chronic subjective tinnitus who received standardized sound therapy. They were randomly split into training (70%) and validation (30%) sets. Using the training set, feature selection was performed via Least absolute shrinkage and selection operator (LASSO) regression, and independent predictors were identified by multivariate logistic regression. The key variables were used to build the machine learning model, and the optimal model was determined based on the area under the receiver operating characteristic curve (AUC), calibration degree, and decision curve analysis (DCA) performance. A nomogram was created for visualization, and SHAP (SHapley Additive exPlanations) values were applied to interpret the model.

Results: A total of 342 patients were randomized into a training set (n = 239, 70%) and a validation set (n = 103, 30%). Multivariate logistic regression identified tinnitus duration, Tinnitus Functional Index (TFI) score, and Generalized Anxiety Disorder-7 (GAD-7) score as independent risk factors for treatment non-response, while previous treatment history, residual inhibition duration, uncomfortable loudness level, and Tinnitus Acceptance Questionnaire (TAQ) score were independent protective factors. Machine learning model comparisons revealed that the random forest model achieved the highest predictive performance (AUC = 0.870), outperforming support vector machine (0.801), K-nearest neighbors (0.812), and gradient boosting (0.807) models. The model also showed good calibration and provided a positive net benefit across a wide range of threshold probabilities on decision curve analysis. SHAP-based interpretability analysis confirmed the direction and magnitude of each feature's contribution, aligning with the multivariate regression results and enhancing the model's clinical plausibility.

Conclusion: In conclusion, the developed nomogram integrates audiological and psychometric variables to individually predict sound therapy outcomes in tinnitus patients. This model serves as a practical tool for optimizing patient selection and personalizing intervention strategies, which may ultimately improve clinical efficacy and resource allocation.

Background: Female hormone therapy [FHT, birth control treatment and postmenopausal hormone replacement therapy (HRT)] is not withheld from patients with cerebral cavernous malformations (CCM), notwithstanding the uncertainty surrounding the impact of these medications on the risk of intracranial hemorrhage (ICH). This study aimed to evaluate the impact of female hormone therapy on the risk of ICH or focal neurological deficit (FND) in patients with CCM.

Methods: The prospective institutional database was examined for all patients with CCM treated at our institution between 2006 and 2023. Inclusion criteria comprised patients with confirmed CCM diagnosis through radiological and/or histological examination, availability of baseline clinical characteristics, accessible medication history, and follow-up data. Patients were stratified based on their medical treatment regimen, which included female hormone therapy or no treatment. The study assessed the time-to-event probability and the number of events (ICH or FND) during the follow-up period.

Results: A total of 328 female patients with CCM were included in the final analysis. Among them, 56 patients (17.1%) were receiving female hormone therapy. Specifically, 37 patients (11.3%) were using birth control treatments and 19 patients (5.8%) were on HRT. The mean number of ICH per patient was 0.43 (SD 1.11) in the FHT group and 0.38 (SD 0.8) in the control group (p = 0.1), while the mean number of FND was 0.36 (SD 0.84) in the FHT group and 0.28 (SD 0.66) in the control group (p = 0.58). The time to first ICH was 1631.5 days (SD 2324.6) in the FHT group and 1161.4 days (SD 1650.8) in the control group (p = 0.35), while the time to first FND was 1601.0 days (SD 1934.1) in the FHT group and 1208.1 days (SD 1649.5) in the control group (p = 0.86).

Conclusion: The study shows that female patients with a diagnosis of cerebral cavernous malformation receiving female hormone therapy do not experience a significant higher likelihood of intracranial hemorrhage or focal neurological deficit. These findings indicate that, despite the observed tendency, female hormone therapy does not significantly alter the risk of these events in the observed female patients.

Background: Gastrointestinal dysfunction (GID) is increasingly recognized in neurocritical care, but disease-specific epidemiology, associated clinical factors, and outcomes in aneurysmal subarachnoid hemorrhage (aSAH) remain insufficiently characterized. We aimed to quantify the prevalence of GID in patients with aSAH, identify its clinical associations, and evaluate its prognostic implications.

Methods: We conducted a 15-year retrospective cohort study involving consecutive adults with aSAH who were admitted to the neurological intensive care unit (NICU) at West China Hospital (24 October 2009-29 June 2024). GID was defined pragmatically as the presence of the following symptoms/signs: gastric residual volume [GRV] ≥ 500 mL on any calendar day after enteral nutrition initiation, gastrointestinal bleeding, or Bristol-defined diarrhea. GID occurrence was modeled using Fine-Gray competing-risk analysis (with in-hospital death as the competing event). In-hospital mortality was analyzed using multivariable logistic regression. Thirty-day survival was described by Kaplan-Meier (KM) curves.

Results: Among the 994 patients with aSAH, GID occurred in 44.8% (445/994). Compared to non-GID patients, those with GID had higher admission heart rates and temperature levels, along with a greater proportion having a Hunt-Hess (HH) score ≥4 (43% vs. 20%, p < 0.001). Patients with GID had significantly longer ICU (18.5 ± 14.8 vs. 6.2 ± 5.7 days) and hospital stays (26.5 ± 20.5 vs. 12.7 ± 8.4 days) and higher in-hospital mortality (37% vs. 22%, p < 0.001). The GID group also had higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (1576.76 ± 3237.84 vs. 1251.52 ± 2673.15, p = 0.023), C-reactive protein (CRP) (62.64 ± 69.30 vs. 39.84 ± 56.95, p < 0.001), interleukin-6 (IL-6) (136.03 ± 355.40 vs. 77.64 ± 182.79, p < 0.001), and procalcitonin (PCT) (1.07 ± 5.71 vs. 0.56 ± 2.88, p < 0.001). In the multivariable Fine-Gray competing-risk analysis, nasojejunal tube use, arrhythmia, target temperature management, HH ≥ 4, and GI drug exposure were associated with a higher subdistribution hazard of GID. KM curves showed lower unadjusted 30-day survival in the GID group (log-rank p < 0.0001). GID was not independently associated with in-hospital mortality in multivariable analyses.

Conclusion: In aSAH, GID is common and correlates with neurological severity, autonomic dysregulation, systemic inflammation, and resource use. Although GID is not independently associated with mortality after adjustment, it identifies a high-risk subgroup and supports early, structured gastrointestinal supportive strategies in neurocritical care.

Background: The monocyte-to-albumin ratio (MAR) integrates systemic inflammation and nutritional status derived from routine laboratory data. We assessed whether the admission MAR is associated with 3-month functional outcomes following acute ischemic stroke (AIS).

Methods: We conducted a single-center, retrospective cohort study of consecutive adults with AIS admitted within 3 days of symptom onset (October 2023-March 2024). MAR was calculated from the admission monocyte counts and serum albumin levels. The primary outcome was poor 3-month functional status, defined as a modified Rankin Scale (mRS) score ≥3. Associations between MAR and outcomes were examined using multivariable logistic regression (with and without adjustment), smooth curve fitting, and prespecified subgroup analyses (sex, age, smoking status, drinking status, hypertension, diabetes status, eGFR, and TOAST subtype).

Results: Among 395 patients (mean age 66.2 years; 34.7% female), 59 (14.9%) had poor outcomes. A higher admission MAR independently predicted poor outcomes: per 1-unit increase, the adjusted odds ratio (OR) was 1.13 (95% CI 1.07-1.20; p < 0.001). Compared with the low tertile, patients with the high tertile had significantly greater odds (OR 3.21; 95% CI 1.25-8.20) with a linear trend (P for trend = 0.006). Smooth curve fitting demonstrated a largely monotonic increase in risk across the observed MAR range. Associations were consistent across subgroups with no significant interactions (all interactions p > 0.05). With respect to the TOAST subtype, the MAR remained significant for large-artery atherosclerosis (OR 1.10; 95% CI 1.02-1.20) and small-artery occlusion (OR 1.23; 95% CI 1.07-1.42), but not for cardioembolism.

Conclusion: The admission MAR is independently and positively associated with poor 3-month functional outcomes after AIS. MAR is a promising tool for early risk assessment when it is integrated with established predictors.

Background: The co-occurrence of Alzheimer's disease and related dementias (ADRD) with hyperlipidemia represents a growing public health burden amid population aging. Although both conditions have been independently linked to increased morbidity and mortality, national trends in ADRD-related mortality involving hyperlipidemia remain poorly characterized.

Methods: We conducted a retrospective, population-based study using mortality data from the U.S. Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) from 1999 to 2020. Deaths with co-listed International Classification of Diseases, Tenth Revision codes for ADRD and hyperlipidemia were identified. Age-standardized mortality rates (ASMR) were calculated per 100,000 persons using the 2000 U.S. standard population. Joinpoint regression was employed to estimate annual percentage change (APC) and average annual percentage change (AAPC) with 95% confidence intervals (CI).

Results: Between 1999 and 2020, the number of deaths related to ADRD with hyperlipidemia increased from 519 to 21,969, with the ASMR rising from 0.19 to 5.32 per 100,000 (AAPC: 15.25%; 95% CI: 14.37-17.31). A sharp rise in mortality was observed after 2018 across nearly all subgroups. Males had a steeper increase than females (AAPC: 16.31% vs. 14.97%). Non-Hispanic Black individuals had the highest ASMR in 2020 (5.53 per 100,000), while Asian/Pacific Islanders had the most rapid increase (AAPC: 21.80%). Regionally, the South showed the highest burden, while the Northeast exhibited the fastest growth (AAPC: 17.77%). Rural areas had a higher ASMR than metropolitan areas (6.29 vs. 5.09 per 100,000), with comparable upward trends. Notably, individuals aged ≥85 years accounted for over half of all deaths by 2020 and exhibited the highest age-specific mortality rates.

Conclusion: ADRD-related mortality involving hyperlipidemia has significantly risen in the U.S. over two decades, with notable disparities across demographics and geography, underscoring the need for public-health relevance and coordination to be evaluated in future analytic studies targeting cardiometabolic and cognitive health in high-risk populations.

Background: Low back pain and radiculopathy due to lumbar intervertebral disc herniation are prevalent conditions, significantly impacting quality of life and imposing substantial socioeconomic burdens globally. In Korea, these conditions are frequently managed within traditional Korean medicine clinics, demonstrating high patient preference for such interventions. However, rigorous clinical evidence on the effectiveness, cost-effectiveness, and safety of individual traditional Korean medicine therapies remains insufficient, particularly for older adult populations where surgical risks are elevated. This highlights a critical need for research into conservative treatment approaches, especially pragmatic randomized controlled trials that reflect real-world clinical practice.

Methods: This pragmatic randomized controlled trial will be a two-arm parallel study designed to evaluate the effectiveness and safety of herbal medicine therapy for low back pain and radiculopathy resulting from lumbar intervertebral disc herniation. Seventy-four eligible adult participants, aged 19 years or older, with magnetic resonance imaging or computed tomography confirmed disc bulging or worse and a Numeric Rating Scale score for radiating pain between three and six, will be randomly assigned to either the herbal medicine strategy treatment group or a usual traditional Korean medicine treatment group that excludes herbal medicine. The primary outcomes will be changes in the Numeric Rating Scale for radiating pain and the Oswestry Disability Index at week seven. Secondary outcomes will include various pain, disability, quality of life, and economic evaluation measures assessed at multiple time points up to 26 weeks. Safety will be continuously monitored through adverse event reporting, laboratory tests, and vital signs. Statistical analysis will primarily use intention-to-treat and per-protocol populations, employing linear mixed models for efficacy endpoints and chi-squared or Fisher's exact tests for safety data. Non-inferiority testing will be performed if superiority is not established.

Conclusion: This pragmatic randomized controlled trial aims to provide robust clinical evidence on the effectiveness, safety, and cost-effectiveness of herbal medicine therapy for lumbar intervertebral disc herniation, particularly in comparison to other traditional Korean medicine interventions. The findings are expected to contribute significantly to developing evidence-based guidelines and optimizing treatment strategies for this prevalent condition, addressing an urgent healthcare need and improving patient outcomes.

Introduction: Spinal cord injury (SCI) is a severe condition characterized by neuroinflammation and oxidative stress, which hinder neurological recovery. Polyethylene glycol (PEG) has shown multiple therapeutic benefits in SCI, such as repairing axonal membranes, improving the post-injury microenvironment, preventing nerve fiber degeneration, and inhibiting spinal cord vacuolation and scar formation. Based on these properties, PEG is regarded as a potential fusogen capable of promoting functional recovery after SCI. This study aimed to further investigate the effects of PEG on SCI and elucidate its underlying molecular mechanisms using a mouse spinal cord total transection model.

Methods: A mouse model of complete spinal cord transection was established to evaluate the therapeutic potential of PEG. Motor function recovery was assessed using the Basso Mouse Scale (BMS) and footprint analysis. Oxidative stress levels were measured via superoxide dismutase (SOD) and malondialdehyde (MDA) assay kits, while inflammatory cytokine expression was analyzed using enzyme-linked immunosorbent assay (ELISA). Histopathological examination was performed to evaluate axonal and myelin preservation and cystic vacuole formation. Immunofluorescence staining was used to observe axonal regeneration and neuroprotection. Additionally, electrophysiological tests were conducted to assess the recovery of nerve conduction.

Results: Mice treated with PEG showed significantly improved BMS scores at 7, 14, and 28 days post-injury compared to the untreated SCI group, indicating enhanced motor function recovery. Biochemical assays revealed that PEG markedly reduced oxidative stress and suppressed the expression of pro-inflammatory cytokines during the early phase of SCI. Histopathological analysis demonstrated that PEG treatment protected spinal cord axons and myelin tissue and significantly reduced the formation of cystic vacuoles. Immunofluorescence results indicated that PEG exerted neuroprotective effects and promoted axonal regeneration after SCI. Electrophysiological assessments further confirmed improved recovery of nerve conduction in PEG-treated mice.

Discussion: The findings of this study demonstrate that PEG, as a fusogen, exhibits significant neuroprotective and regenerative effects when applied immediately after SCI. PEG not only attenuated oxidative stress and neuroinflammation but also preserved axonal integrity, promoted myelin protection, and enhanced functional recovery. These results suggest that early application of PEG represents an innovative and promising therapeutic strategy for SCI, warranting further investigation into its long-term efficacy and potential clinical translation.

Background: Aerobic exercise, as a non-pharmacological intervention, has been widely recognized for its potential benefits on cognitive function in individuals with mild cognitive impairment (MCI). However, systematic evidence regarding its effects on other critical health domains, such as sleep quality and quality of life, remains limited. Moreover, previous meta-analyses have typically included a relatively small number of randomized controlled trials (RCTs), which may constrain the generalizability and objectivity of their findings.

Objective: This study aimed to evaluate the effects of aerobic exercise on cognitive function, sleep quality, and quality of life in older adults with MCI, and to identify key exercise prescription parameters based on the FITT principle (frequency, intensity, time, and type).

Results: A total of 26 randomized controlled trials involving 2,085 individuals with MCI were included. The meta-analysis revealed that aerobic exercise had a statistically significant positive effect on global cognitive function (SMD = 0.81, 95% CI: 0.58-1.05, p < 0.00001) and quality of life (SMD = 1.26, 95% CI: 0.70-1.82, p < 0.00001). However, no significant improvement was observed in sleep quality (SMD = 0.07, 95% CI: -1.79-1.93, p = 0.94). Subgroup analysis further indicated that interventions conducted four times per week, lasting more than 50 min per session, at moderate intensity, and primarily involving walking were most effective in improving cognitive function.

Conclusion: The findings of this study demonstrate that aerobic exercise may significantly improve cognitive function and quality of life in older adults with MCI, with enhanced effects observed when intervention parameters are optimized.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024495979, Unique Identifier: CRD42024495979.

Introduction: Accurate segmentation of brain regions in magnetic resonance imaging (MRI) is essential for diagnosing and managing neurological diseases. FreeSurfer is a widely used tool for brain MRI segmentation, but its limitations in speed and usability pose challenges in clinical practice. Neurophet AQUA, an advanced automated segmentation tool, aims to overcome these challenges by offering rapid and reliable segmentation. This study evaluates two segmentation pipelines: (1) a T1-based brain region segmentation pipeline, comparing the performance and reliability of Neurophet AQUA and FreeSurfer v7.3.2 using the standard recon-all pipeline in segmenting gray matter, white matter, and subcortical structures; and (2) a T2-FLAIR-based white matter lesion segmentation pipeline of Neurophet AQUA, assessing the detection of white matter hyperintensities (WMH).

Methods: Four main datasets were used. For the T1-based segmentation pipeline, the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset was used to compare the segmentation results of Neurophet AQUA and FreeSurfer, with quality assessed by expert evaluation. The MarkVCID dataset was used to evaluate the scan-rescan repeatability and inter-scanner reproducibility of Neurophet AQUA. For the T2-FLAIR-based pipeline, WMH segmentation performance was assessed using 2D and 3D FLAIR sequences from the ADNI dataset by comparing the segmentations to ground truth (GT) labels and calculating Dice similarity coefficients (DSC).

Results: Segmentation quality and reliability showed that Neurophet AQUA and FreeSurfer achieved comparable performance in most regions, with no significant differences. However, Neurophet AQUA had significantly faster processing time. In intracranial volume (ICV) measurements, Neurophet AQUA showed better repeatability than FreeSurfer in both rescans (ICC: 0.999 vs. 0.991) and inter-scanner settings (ICC: 0.983 vs. 0.866). AQUA also demonstrated consistent WMH segmentation across 2D and 3D FLAIR images.

Conclusion: Neurophet AQUA demonstrated high segmentation accuracy and excellent repeatability in rescanned measurements, as well as exploratory evidence of inter-scanner reproducibility on T1-weighted MRI, showing comparable performance to established tools such as FreeSurfer. It also showed consistent WMH segmentation across FLAIR types. Neurophet AQUA is highly suitable for clinical applications that require accurate analysis, high repeatability and reproducibility, and rapid brain MRI processing, making it particularly well-suited for multicenter research studies.

Background: Despite successful mechanical thrombectomy (MT), futile reperfusion (FR) remains a major challenge in acute ischemic stroke (AIS). While post-MT hyperdense areas (HDAs) on non-contrast computed tomography (CT) are associated with reperfusion injury, the differential effects of anatomical HDA subtypes-deep intraparenchymal (DIH) versus subarachnoid/cortical (SCH)-on FR risk are unclear.

Methods: We retrospectively analyzed 864 AIS patients undergoing MT (2017-2023). HDAs detected within 0.5 h post-MT were classified as DIH or SCH. Propensity score matching (PSM) balanced baseline confounders (1:1 DIH: SCH). Risk factors for FR were analyzed using a multivariate logistic regression analysis in the PSM cohort.

Results: After PSM, 116 patients in the DIH group were matched with 116 patients in the SCH group. In total, 91 patients (78.5%) in the SCH group and 72 patients (62.1%) in the DIH group suffered FR (p = 0.006). A multivariate analysis showed that SCH significantly increased the risk of FR (OR: 3.103, 95%CI: 1.425-6.759, p = 0.004), indicating that patients with SCH have a 3.103 times higher risk of FR than patients with DIH.

Conclusion: Anatomical HDA subtypes differentially predict FR risk, with SCH portending a worse prognosis. This subtype classification enables early risk stratification and may guide personalized post-MT management.