ABSTRACTAimsTo summarize the anatomo‐electro‐clinical characteristics of parietal lobe epilepsy (PLE) subgroups using unsupervised cluster analysis.MethodsThis retrospective cohort study included patients with drug‐resistant PLE with seizure freedom after surgery and evaluated scalp video‐electroencephalography (EEG) recordings from three epilepsy centers. Hierarchical cluster analysis associated interictal/ictal patterns and initial ictal semiology with anatomical subgroups.ResultsWe analyzed 79 interictal EEG, 141 ictal EEG, and 141 semiological patterns in 47 patients. Cluster analysis associated interictal and ictal discharges from lateral superior parietal lobule epilepsy with centroparietal region distributions on scalp EEG, whereas discharges from other subgroups involved broader regions. Cluster heatmaps of the initial ictal semiology showed: Chapeau de gendarme, affective phenomena, and forced eye deviation in intraparietal sulcus; contralateral limb tonic/clonic or akinetic, affective phenomena, and visual illusions in SPL‐lateral; Chapeau de gendarme, behavioral arrest, and vestibular in parieto‐occipital sulcus; behavioral arrest in angular gyrus; distal gestural automatisms and cephalic sensations in posterior cingulate; body‐perception illusion and contralateral versive in supramarginal gyrus; contralateral facial tonic/clonic in parietal operculum.ConclusionPLE subgroups exhibited distinct scalp EEG features and ictal semiology, reflecting unique propagation networks and highlighting the importance of detailed video‐EEG for identifying the epileptogenic zone and guiding intracranial electrode placement.

ABSTRACTBackgroundDepression is associated with adverse effects in patients with autoimmune hepatitis (AIH). However, the underlying mechanism remains unclear. This study explores the impact of depression and related intestinal microbiota on immune‐mediated hepatitis.MethodsWe assessed depression in 260 AIH patients receiving 2‐year standardized treatment and 173 healthy controls. In mice, depressive‐like behaviors were induced by chronic unpredictable mild stress (CUMS), and immune‐mediated hepatitis was induced by intravenous injection of concanavalin A (ConA). Fecal microbiota transplantation (FMT) was performed using samples from patients with major depressive disorder (MDD) and controls.ResultsDepression was common in patients with AIH (106/260, 40.8%) and was associated with cirrhosis. Compared with nondepressed AIH patients, those with depression showed exacerbated intestinal barrier dysfunction and hepatic NLR family pyrin domain containing 3 (NLRP3) inflammasome overactivation. In the ConA‐induced hepatitis model, CUMS exposure aggravated these abnormalities, which were then attenuated by mirtazapine. Furthermore, mice colonized with MDD microbiota exhibited greater intestinal barrier disruption and hepatic NLRP3 inflammasome overactivation than those colonized with control microbiota. Notably, gut‐derived Lactococcus formosensis, isolated from the livers of MDD microbiota‐colonized mice, could translocate to the liver and induce hepatic NLRP3 inflammasome overactivation. In addition, vaccination against L. formosensis prevented translocation and alleviated liver injury in monocolonized mice.ConclusionDepression aggravates immune‐mediated hepatitis through disruption of intestinal barrier integrity and overactivation of hepatic NLRP3 inflammasome. Gut‐derived L. formosensis could translocate to the liver and induce liver injury in mice. This study provides the necessity of screening for depression in patients with AIH.

ABSTRACTBackgroundPost‐stroke cognitive impairment (PSCI) is a common yet frequently overlooked complication that adversely affects recovery and long‐term outcomes in stroke survivors. Early identification of individuals at risk is essential for timely cognitive rehabilitation.ObjectiveThis study aimed to investigate the association between carotid atherosclerosis indicators—specifically, carotid plaque burden and degree of carotid artery stenosis—and the occurrence of PSCI in patients with mild acute ischemic stroke (AIS), using carotid ultrasound as a cost‐effective, widely accessible diagnostic modality.MethodsA prospective cohort of 181 patients diagnosed with AIS within 7 days of onset was enrolled. Baseline demographics, clinical characteristics, and carotid ultrasound parameters were collected. PSCI was assessed at 6 months using the Montreal Cognitive Assessment (MoCA). Binary logistic regression was used to identify independent predictors of PSCI. The predictive accuracy of individual and combined markers was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsAmong 181 participants, 75 (41.4%) were diagnosed with PSCI at the 6‐month follow‐up. Multivariate analysis revealed that the carotid plaque Crouse score (OR = 1.157, 95% CI: 1.055–1.269) and severe carotid artery stenosis (OR = 3.733, 95% CI: 1.582–8.811) were independently associated with PSCI. ROC analysis demonstrated modest predictive performance for the Crouse score (AUC = 0.667) and stenosis (AUC = 0.596), while a multivariable model incorporating clinical and ultrasound parameters achieved an AUC of 0.818 (95% CI: 0.758–0.877). Significant between‐group differences were observed in AVLT‐I, AVLT‐II, VFT, TMT‐B, CDT, and MoCA subdomains (p < 0.05).ConclusionCarotid plaque burden and severe carotid stenosis are independently associated with the development of PSCI in patients with mild AIS. Carotid ultrasound, combined with clinical risk factors, may provide a practical approach for early identification and risk stratification of PSCI.Trial Registration: Chinese Clinical Trial Registry (ChiCTR1900022675); URL: https://www.chictr.org.cn/

ABSTRACTBackgroundAcute subdural hematoma (ASDH) is a severe complication of traumatic brain injury, with high mortality and disability. Spontaneous hematoma resolution is an important determinant of functional recovery, but the biological mechanisms underlying this process remain poorly understood. Coagulopathy, common in ASDH, may influence hematoma dynamics, but its causal role remains uncertain.MethodsWe conducted a two‐sample Mendelian randomization (MR) study to investigate the causal effects of coagulation traits on hematoma resolution. Genetic instruments for fibrinogen isoforms, coagulation factors VIII, XI, V, VII, natural anticoagulants, and platelet traits were obtained from large genome‐wide association studies. Due to the absence of ASDH‐specific GWAS data, we used genetic susceptibility to intracerebral hemorrhage (ICH) and poststroke functional outcome as indirect proxies for hematoma persistence and clearance. We acknowledge that these proxies cannot fully capture the unique pathophysiology of ASDH, but they represent pragmatic, biologically relevant surrogates. Causal estimates were obtained using inverse‐variance weighted MR with robust sensitivity analyses.ResultsGenetically higher fibrinogen γ' levels were associated with increased odds of hematoma resolution (OR 1.25, 95% CI 1.10–1.42). Higher factor VIII and XI levels were associated with reduced odds of Resolution (OR 0.82, 95% CI 0.72–0.94; OR 0.88, 95% CI 0.78–1.00). Secondary analyses using poststroke functional outcome yielded similar patterns but did not reach statistical significance (OR ~1.10, p = 0.15).ConclusionsOur findings provide genetic evidence suggesting coagulation pathways, particularly fibrinogen γ' and factors VIII and XI, may influence hematoma resolution in ASDH. However, due to the indirect nature of the proxies used, these results should be considered hypothesis‐generating and require further validation in ASDH‐specific cohorts.

ABSTRACTBackgroundPrevious studies have reported functional alterations in the brains of patients with rhegmatogenous retinal detachment (RRD). However, it remains largely unclear whether RRD affects hemispheric specialization and interhemispheric coordination, and how these alterations relate to underlying gene expression patterns and neurotransmitter receptor distributions.MethodsWe employed the Autonomy Index (AI) and Connectivity between Functionally Homotopic Voxels (CFH) to quantify alterations in hemispheric specialization and interhemispheric cooperation in patients with RRD. Transcriptome–neuroimaging spatial correlation analysis was performed by integrating gene expression data from the Allen Human Brain Atlas (AHBA) to identify genes associated with AI and CFH alterations. Enrichment and protein–protein interaction analyses were conducted to characterize the biological processes and molecular features of these genes. Furthermore, we explored the spatial associations between AI/CFH abnormalities and neurotransmitter receptor distributions. Finally, a support vector machine (SVM) classifier combined with Shapley additive explanations (SHAP) was implemented to distinguish RRD patients from healthy controls (HCs) and to determine the most discriminative brain regions.ResultsRRD patients exhibited significant alterations in AI and CFH within the frontal lobe, occipital lobe, and thalamus. Transcriptome–neuroimaging integration revealed gene sets closely associated with these abnormalities. These genes were primarily enriched in key biological processes including synaptic signaling, sensory organ development, Notch signaling, and structural neuroplasticity. The spatial pattern of CFH changes showed strong alignment with the regional distributions of multiple neurotransmitter systems, particularly serotonergic, dopaminergic, glutamatergic, and cholinergic pathways. Finally, the SVM–SHAP classification framework identified CFH in the right thalamus as the most discriminative feature for differentiating RRD patients from HCs.ConclusionThese findings deepen our neurobiological understanding of RRD‐induced brain functional remodeling and provide theoretical support and a methodological foundation for developing central intervention strategies and potential discriminative imaging tools for retinal diseases.

ABSTRACTAimsThis study aimed to investigate the association between autonomic activity, assessed by 24‐hour heart rate variability (HRV), and the development of perihematomal edema (PHE) as well as 3‐month functional outcomes following intracerebral hemorrhage (ICH).MethodsWe retrospectively included patients with ICH who underwent 24‐hour electrocardiographic (ECG) monitoring within 14 days of onset from a prospective cohort. HRV parameters were calculated from ECG data. A poor functional outcome at 3 months was defined as a modified Rankin Scale (mRS) score ≥ 3. PHE volume was measured on 7‐day computed tomography scans using 3D Slicer software, and adverse PHE was defined as relative PHE (edema volume/hematoma volume) ≥ 2. Univariate and multivariate logistic regression analyses were performed to identify predictors of adverse PHE and poor outcomes. Partial correlation analysis was conducted to examine the association between HRV parameters and adverse PHE. Five machine‐learning algorithms were applied to develop predictive models for 3‐month poor outcomes.ResultsA total of 312 patients were included, of whom 45.2% (141/312) had poor outcomes at 3 months and 48.6% (122/251) had adverse PHE. Parasympathetic hypoactivity, indicated by low high‐frequency power, was independently associated with poor 3‐month outcomes. In addition, parasympathetic hypoactivity (measured by the root mean square of successive differences between adjacent NN intervals) and relative sympathetic hyperactivity (measured by the ratio of low‐frequency to high‐frequency power) independently predicted adverse PHE. Among the machine‐learning models, the eXtreme Gradient Boosting (XGBoost) algorithm achieved the highest predictive performance for poor 3‐month outcomes, with an AUC of 0.883.ConclusionsTwenty‐four–hour parasympathetic hypoactivity is associated with adverse PHE and poor functional outcomes following ICH.

ABSTRACTBackgroundPD‐1 inhibitors have revolutionized cancer immunotherapy but present significant neurological safety concerns. While clinical trials have documented neurological adverse events (nAEs), a comprehensive understanding of their patterns and risk factors remains limited. This study systematically analyzed a decade of FAERS data to investigate PD‐1 inhibitor–associated neurotoxicities.MethodsUsing FAERS data (2014–2024), we conducted disproportionality analyses (ROR, IC, PRR) to assess PD‐1 inhibitor–nAE associations. Risk factors were evaluated using logistic regression; timing analyses used log‐rank and Mann–Whitney U tests, while group comparisons used Chi‐square tests.ResultsAmong 115,000 PD‐1 inhibitor–associated adverse events, 7968 (6.93%) involved nAEs, showing an increasing trend from 4.96% (Q4 2014) to 7.67% (Q1‐Q2 2024). PD‐1 inhibitors showed significant nAE signals (ROR: 1.21, 95% CI: 1.18–1.23), with cemiplimab showing the strongest association (ROR: 1.38, 95% CI: 1.18–1.62). The most common nAEs were dizziness (N = 942, 10.3%), encephalitis (N = 435, 4.8%), and cerebrovascular accident (N = 451, 4.9%). Risk factors included age > 65 years (OR: 1.10), female sex (OR: 1.04), skin cancer (OR: 1.36), and nervous system cancers (OR: 1.44). The median onset time was 34 days (IQR: 12–104), with 63.8% occurring within 2 months and 59% resulting in severe outcomes.ConclusionThis study reveals a spectrum of PD‐1 inhibitor–related neurological toxicities, mainly involving central nervous system dysfunction, providing important insights into risk patterns and timing characteristics. These findings support improved clinical monitoring practices and inform the development of personalized patient care strategies.

ABSTRACTBackgroundThis study aimed to identify neurobiomarkers that predict the efficacy of treatment of cognition in patients with bipolar disorder (BD).MethodsRegional homogeneity (ReHo) and degree centrality (DC) values, which are two functional magnetic resonance imaging indicators, were analyzed to compare differences in brain activities between patients with BD and healthy controls (HC).ResultsBD patients (N = 92) exhibited increased activity in the right hippocampus or right parahippocampal gyrus compared to HC, while their ReHo and DC values in the left middle frontal gyrus decreased in the resting state. The delayed memory scores were predicted by using connectome‐based predictive modeling in patients with BD at baseline. After 12 weeks of treatment, the patients with BD, whose cognitive function improved (n = 24), showed activity in the right superior temporal gyrus (STG) and left anterior cingulate cortex (ACC) at baseline. The improvement in cognitive function of patients with BD is distinguished by abnormal activities using support vector machine analysis.ConclusionsThe abnormal frontal‐limbic network plays a critical role in the underlying neuropathological mechanism of cognitive impairment in patients with BD. The right STG and left ACC hold the potential to serve as neurobiomarkers for predicting the clinical efficacy of cognitive function treatment. These regions provide additional target options for future physical treatments of cognitive impairment in patients with BD.

ABSTRACTBackgroundGlioblastoma (GBM) is one of the most aggressive and treatment‐resistant primary brain tumors, with the mesenchymal subtype exhibiting particularly poor prognosis. Tumor electric field therapy (TEFT) has emerged as a promising adjunctive treatment, but its underlying molecular mechanisms remain incompletely understood.MethodsGBM functional states were analyzed using CancerSEA datasets. GBM cell lines were treated with 200 kHz TEFT at 2.2 V/m for 72 h. C1R was knocked down using siRNA and shRNA. Cell morphology, migration, invasion, proliferation, and signaling pathways were assessed through various assays. Findings were validated in animal models and clinical specimens.ResultsC1R was identified at the intersection of TEFT‐downregulated genes, poor prognosis markers, and functional state genes. C1R was significantly upregulated in mesenchymal GBM and strongly correlated with epithelial‐mesenchymal transition (EMT). Single‐cell RNA sequencing revealed C1R was predominantly expressed in MES‐like malignant cells with high EMT signature scores. TEFT treatment induced morphological changes from elongated spindle‐shaped to rounded epithelial‐like morphology, increased E‐cadherin expression, and decreased mesenchymal markers (N‐cadherin, Vimentin, YKL‐40). Mechanistically, TEFT suppressed the TGF‐β/SMAD2/3/STAT3 signaling pathway, downregulating C1R expression. C1R knockdown significantly reduced tumor growth in vivo, while exogenous TGF‐β restored C1R expression and reversed the mesenchymal phenotype in a dose‐ and time‐dependent manner.ConclusionTEFT inhibits GBM progression by suppressing the TGF‐β/SMAD2/3/STAT3/C1R axis, thereby attenuating EMT and reducing tumor aggressiveness. These findings uncover a novel mechanism of TEFT and identify C1R as a potential biomarker and therapeutic target for GBM.

ABSTRACTBackgroundAnti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is frequently associated with long‐term cognitive impairment. However, the underlying mechanisms remain poorly understood, and reliable biomarkers for predicting cognitive outcomes are lacking.MethodsWe established an active immunization mouse model of anti‐NMDAR encephalitis by immunizing with the GluN1356‐385 peptide. Hippocampal proteomic profiling was performed, followed by molecular and histological validation. Behavioral tests were used to assess cognitive function. In parallel, serum and cerebrospinal fluid (CSF) samples were analyzed from a clinical cohort of children with anti‐NMDAR encephalitis to evaluate expression of the targeted biomarker and its association with clinical outcomes.ResultsProteomic analysis and subsequent validation revealed significant upregulation of chitinase‐3‐like protein 1 (CHI3L1) in the hippocampus of model mice, primarily derived from astrocytes. Elevated CHI3L1 levels were observed in parallel with impaired hippocampal neurogenesis, reflected by decreased DCX+ immature neurons and increased SOX2+ neural progenitors. These changes were accompanied by cognitive deficits in behavioral tests. In parallel, we analyzed a pediatric cohort of 83 children with anti‐NMDAR encephalitis. CHI3L1 levels in both serum and CSF were significantly elevated compared to controls. While CHI3L1 levels showed no association with modified Rankin Scale scores at one‐year follow‐up, higher CHI3L1 levels in serum and CSF were significantly correlated with persistent cognitive impairment.ConclusionsOur findings provide preliminary evidence that astrocyte‐derived CHI3L1 may contribute to disrupted hippocampal neurogenesis and cognitive dysfunction in anti‐NMDAR encephalitis. CHI3L1 may serve as a potential biomarker for cognitive prognosis and a therapeutic target for reducing long‐term neurological sequelae.