Preclinical experiments have revealed that Brivaracetam (BRV) exhibited a significant anti-seizure function in animal models and was more effective and safer than other synaptic vesicle protein 2A (SV2A) ligands, including levetiracetam (LEV), this study aims to evaluate the efficacy and safety of generic BRV tablets in Chinese patients with focal-onset seizure. This phase III, randomized, double-blind, placebo-controlled clinical trial conducted in 21 medical centers evaluated BRV (200 mg/day) as an adjunctive therapy in Chinese adult patients with focal-onset seizures, with or without secondary generalization, despite treatment with one or two permitted concomitant anti-seizure medications (ASMs). After an 8-week screening baseline, patients were 1:1 randomized to BRV 200 mg/day or placebo for a 12-week treatment period. The primary efficacy endpoint was the percent reduction in seizure frequency per 28 days from baseline. Safety evaluations included the adverse events (AEs), side effects, and the regular monitoring of clinical symptoms, vital signs, physical examinations, laboratory tests, electrocardiograms, and mood. Of 179 randomized patients, 178 were included in the final analysis (90 in BRV; 88 in placebo), while one patient in placebo group was excluded for not receiving the study drug. The percent reduction in seizure frequency per 28 days from baseline was 40.67

Background Research on tuberous sclerosis complex-associated neuropsychiatric disorders (TAND) in China remains limited. This study aimed to identify determinants of TAND severity to guide clinical management. Methods This multicenter registry-based study included 42 patients with genetically confirmed TSC recruited from nine tertiary hospitals in Henan Province between April 2021 and April 2024. TAND severity was estimated at follow-up using a domain-based scoring framework informed by the TAND checklist. Demographic, epilepsy-related, and genetic factors were analyzed using group comparisons, interaction analysis, univariable linear regression, and hierarchical regression. Results Among 42 patients with TSC, 25 carried TSC2 mutations and 23 had active epilepsy. Total TAND scores were significantly higher in patients with active epilepsy than in seizure-free patients (p < 0.001), and in patients with TSC2 mutations than in those with TSC1 mutations (p = 0.002). A significant interaction between genotype and seizure status was observed for total TAND score (p = 0.038). In hierarchical regression, genotype remained an independent correlate of TAND severity, while each additional year of education was associated with a 1.306-point reduction in total TAND score. Conclusion TSC2 mutation, active epilepsy, and lower educational attainment were associated with greater TAND severity. TSC2 mutation remained independently associated with greater TAND severity after adjustment for epilepsy-related variables, whereas higher educational attainment showed a protective association. These findings support the need for early TAND screening and targeted follow-up in clinically vulnerable patients with TSC.

Objective The aim of this study was to investigate the effect of blood homocysteine (Hcy) levels on the Phase Lag Index (PLI) of electroencephalographic (EEG) resting-state networks (RSNs) in patients with epilepsy (PWEs). Methods Ninety-one patients with newly diagnosed focal epilepsy who had not taken anti-seizure medications (ASMs) were retrospectively included and divided into the Hcy-normal group (Hcy < 15 μmol/L, n = 57) and the Hcy-elevated group (Hcy > 15 μmol/L, n = 34). Nine clinical features were recorded, and 684 PLI features in four bands (α, β, δ, and θ) were calculated. Differences between the two groups of data were compared and correlation analyzed. Results There were significant differences between the two groups in the PLI features of α, β, and δ bands, with O1-Fz (left occipital region-mid frontal region), Fp2-Pz (right frontal pole region-parietal region), and F4-Pz (right frontal region-parietal region) differing significantly in all three bands, and α band was more significantly affected. Correlation analysis showed that α: C4-F8 (right central region-right frontotemporal region), α: T3-Pz (left middle temporal region-parietal region) and δ bands: F3-Fz (left frontal region-middle frontal region). The correlation coefficients were the largest and there was a positive correlation between all statistically significant features and Hcy. Conclusion The present study suggests that Hcy may affect epileptogenesis and seizures by influencing RSNs (especially α band) in specific brain regions, providing a new idea for the study of the Hcy-brain network interaction mechanism in epilepsy.

Diffuse glioma-related epilepsy (dGRE) frequently presents with epilepsy as the initial symptom and is closely associated with tumor progression or recurrence, imposing significant social and psychological burdens on patients. The pathogenesis of dGRE is highly complex, involving both peritumoral microenvironmental mechanisms and tumor-intrinsic factors. Diagnosis requires a comprehensive approach integrating neuroimaging, EEG, molecular biomarkers, and spatial correlation between the tumor and the epileptogenic zone. Management aims to control seizures and improve prognosis. Non-enzyme-inducing anti-seizure medications (ASMs), such as levetiracetam and lacosamide, are recommended as first-line therapy, while valproic acid serves mainly as a second-line agent. Surgical resection, particularly maximal safe and supratotal removal guided by electrophysiological monitoring, significantly improves seizure outcomes. Radiotherapy, chemotherapy, and targeted agents further contribute to seizure control. The updated 2025 Chinese clinical practice guidelines incorporate recent advances in ASM use, postoperative withdrawal strategies, and multidisciplinary treatment algorithms. These updates provide an evidence-based reference for standardized diagnosis and management of dGRE.

Background Post-traumatic epilepsy (PTE) is a common complication of traumatic brain injury (TBI). Studies have indicated that functional abnormalities of the sodium-activated potassium (KNa) channels are closely related to infantile “refractory epilepsy”. However, whether and how the KNa channels are involved in the occurrence of PTE remains unknown. Methods We used adult male C57BL/6 J mice to establish a controlled cortical impact (CCI) mice model with different severity levels. We implanted intracranial electrodes 7 days after injury to observe the spontaneous seizures in the moderately injured mice.vEEG was continuously recorded for 7 days (24 h/day). Then, a multi - electrode array (MEA) was performed 14 days after TBI to evaluate the network activity in the peripheral cortex of TBI lesions.Seven days after injury, we detected the expression of KNa channels around the injury site and the activation of glial cells through immunofluorescence staining. Finally, primary neuron cultures were used to verify whether or not the inflammatory factor upregulated KNa channels and affected neuronal excitability by activating the NF-κB pathway. Results Through continuous vEEG monitoring, we observed abnormal electrographic discharges in the moderate TBI group (9 %, 2/22). MEA recording confirmed hyperactive network around the lesion, supporting that peripheral cortex may be the potential epileptogenic focus. Our findings revealed that expression of KNa channels was elevated in neuronal membranes in the peripheral cortex. Reactive astrocytes and activated microglia were observed in the injured ipsilateral cortex of the moderate and severe TBI mice. In primary neurons, we found that KNa currents were markedly increased after TNF-α stimulation. When the NF-κB signaling pathway was inhibited by SN50, the KNa currents were correspondingly decreased. Conclusions Our results suggest that network hyperactivity in the perilesional neocortex may be the origin of abnormal epileptiform discharge. Activation of glial cells around the lesion releases inflammatory factors that initiate the NF-κB signaling pathway and modulate the KNa channels, which may be a potential mechanism for the occurrence of PTE. This research had important implications for clarifying the origin of epileptic foci of TBI and identifying immune-based biomarkers to improve the prognosis of PTE.

Mucosa‑associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key paracaspase enzyme regulating immune responses, inflammation and oxidative stress. The present study aimed to investigate the effect of MALT1 inhibition on neuroinflammation, neuronal loss and oxidative stress in Alzheimer's disease (AD). A co‑culture system involving microglia and neuron cells under β‑amyloid (Aβ) intervention was used to establish AD cellular models using human microglia HMC3 cells and neuroblastoma SH‑SY5Y cells and mouse microglia BV‑2 and hippocampal neuron HT‑22 cells. The inhibition of MALT1 proteolytic activity was achieved by MALT1 inhibitor 2 (MI‑2) treatment, and the NF‑κB pathway was activated by phorbol 12‑myristate 13‑acetate (PMA) treatment in HMC3 and BV‑2 cells. Western blotting, ELISA, Cell Counting Kit‑8, EdU staining, reactive oxygen species (ROS) detection and reduced glutathione (GSH) assays were performed to evaluate molecular changes, inflammatory responses, neuronal viability and oxidative stress. MALT1 expression was upregulated following Aβ treatment in HMC3 and BV‑2 cells. MALT1 inhibition by MI‑2 suppressed the microglial M1 phenotype but enhanced the M2 phenotype, reduced the levels of the proinflammatory cytokines TNF‑α and IL‑1β and inactivated the NF‑κB pathway in HMC3 and BV‑2 cells. Moreover, microglial MALT1 inhibition elevated cell viability (verified by Cell Counting Kit‑8 and EdU assays), increased the level of reduced glutathione and decreased the levels of reactive oxygen species in SH‑SY5Y and HT‑22 cells. NF‑κB activation by PMA attenuated the effects of MALT1 inhibition on the microglial phenotype switch and proinflammatory cytokine secretion in HMC3 and BV‑2 cells, as well as cell viability and oxidative stress in SH‑SY5Y and HT‑22 cells. The present study reveals that MALT1 inhibition may suppress microglial M1 phenotype, neuroinflammation, neuronal loss and oxidative stress by inactivating the NF‑κB pathway in AD.

BACKGROUND AND OBJECTIVES:Pregnancy alters the pharmacokinetics of antiseizure medications (ASMs). The aim of this study was to quantify gestational changes in ASM concentrations and identify independent covariates among women with epilepsy in China. METHODS:In this prospective, multicenter observational cohort study in China, women with epilepsy aged 18-45 years were enrolled and followed longitudinally. Steady-state trough ASM concentrations were measured, with concentration-to-dose (C/D) ratio as the primary pharmacokinetic parameter. Linear mixed-effects models with model averaging were used to evaluate the independent effects of gestational age, concomitant ASMs, and demographic covariates on ASM C/D ratios. RESULTS:A total of 947 women were included and contributed 1,638 samples between 2019 and 2025, including 1,187 samples collected during nonpregnant periods (821 women, mean age 29.31 ± 8.38 years) and 451 during pregnancy (228 women, mean age 28.67 ± 4.30 years), with 64.3% receiving polytherapy. Lamotrigine exhibited the greatest gestational effect, with C/D ratios declining by 28.8% (β = -0.339; 95% CI -0.508 to -0.339; p < 0.001), 54.3% (β = -0.784; 95% CI -0.938 to -0.629; p < 0.001), and 63.2% (β = -1.001; 95% CI -1.192 to -0.809; p < 0.001) in the first, second, and third trimesters, respectively, reaching a nadir of -65.8% at 32 weeks. Levetiracetam declined by 26.2% (β = -0.303; 95% CI -0.446 to -0.160; p < 0.001), 40.1% (β = -0.512; 95% CI -0.645 to -0.379; p < 0.001), and 31.0% (β = -0.371; 95% CI -0.525 to -0.217; p < 0.001), reaching a nadir of -35.5% at 24 weeks. The metabolite of oxcarbazepine declined by 23.1% (β = -0.262; 95% CI -0.373 to -0.152; p < 0.001), 32.6% (β = -0.394; 95% CI -0.489 to -0.299; p < 0.001), and 44.3% (β = -0.585; 95% CI -0.695 to -0.475; p < 0.001). Lacosamide significantly decreased in the second trimester (-10.8%; β = -0.207; 95% CI -0.399 to -0.014; p = 0.035). Perampanel showed an increasing trend but was limited by sample and polytherapy. Concomitant ASMs primarily shifted baseline C/D ratios without altering gestational changes, and several drug-drug interactions were identified. Higher body weight was associated with lower C/D ratios for most ASMs, except for perampanel. Interindividual variability remained the dominant factor determining C/D ratios over measured covariates. DISCUSSION:Pregnancy was the primary driver of declining C/D ratios, and concomitant ASMs and body weight acted as secondary modifiers. These findings support individual therapeutic drug monitoring. TRIAL REGISTRATION INFORMATION:ChiCTR2100046318 (Chinese Clinical Trial Registry, chictr.org.cn).

Objective Constructing a classification model based on 3 nonlinear features of scalp electroencephalography (SEEG) for identifying the preictal phase of epilepsy. Methods Total 83 patients with epilepsy who underwent long-term SEEG monitoring at He'nan Provincial People's Hospital from January 2014 to December 2021 were enrolled. Three nonlinear features [phase lag index (PLI), Lempel-Ziv complexity (LZC) and sample entropy (SampEn)] were calculated. Analysis of variance, rank sum test, and χ2 test were used to complete feature selection of disease predictive value. Single and general models were constructed to identify the preictal phase of epilepsy, respectively, using different machine learning (ML) algorithms including support vector machine (SVM), light gradient boosting machine (LightGBM), and k nearest neighbor (KNN) methods based on five-fold cross-validation. Results The LightGBM model constructed with rank sum test feature selection (α+β+δ+θ+whole) performed best. The average performance in the single model was 0.929 for sensitivity, 0.924 for specificity, 0.934 for accuracy, 0.930 for precision, 0.928 for the F1-score, and 0.971 for the area under the curve (AUC). In the general model, the performance was 0.712 for sensitivity, 0.652 for specificity, 0.682 for accuracy, 0.677 for precision, 0.694 for the F1-score, and 0.766 for AUC. Conclusions The LightGBM model constructed using rank sum test was effective in identifying the preictal phase of epilepsy.

Methods We recruited 31 sporadic PKD patients and 10 familial pedigrees from the Departments of Neurology at Henan Provincial People’s Hospital between June 2023 and April 2025. Whole-exome sequencing (WES) was performed to identify pathogenic variants, followed by Sanger sequencing for validation and segregation analysis. In silico structural modeling and protein stability analyses were conducted for missense variants. A systematic literature review was performed to further characterize TMEM151A -related PKD. Results Three TMEM151A variants were identified in one sporadic case and two familial pedigrees, including two novel missense variants (c.894G > T [p.Trp298Cys] and c.899T > C [p.Leu300Pro]) and one frameshift variant (c.943dup[p.Val315GlyfsTer31]. Notably, in one pedigree, the variant carrier presented with epilepsy without PKD, indicating phenotypic heterogeneity and incomplete penetrance. Structural analyses suggested that missense variants may impair protein stability by altering hydrogen bonding networks. Combined with 74previously reported cases, TMEM151A -related PKD typically presents with adolescent onset, brief dystonic episodes, and a favorable response to sodium channel blockers. No significant differences in age at onset or remission were observed between truncating and missense variants, suggesting a shared pathogenic mechanism. Conclusions This study expands the mutational spectrum of TMEM151A by identifying three previously unreported variants and further refines the clinical characterization of TMEM151A -associated PKD. Our findings support that mutation type is not a major determinant of clinical phenotype, implicating a potential common mechanism such as haploinsufficiency.

CDGSH iron sulfur domain 1 (CISD1) plays important roles in regulating cellular iron and reactive oxygen species (ROS) homeostasis. This study aimed to investigate the effect of CISD1 on neuronal ferroptosis in Alzheimer’s disease (AD) cellular models, and the implication of AMPK pathway during this process. CISD1 expression in brain tissues from AD patients and controls was obtained from AlzData public database. HT22 and SH-SY5Y cells were challenged with amyloid-beta (Aβ) to construct AD cellular models. CISD1 or negative-control (NC) overexpression plasmids were transfected into AD cellular models; afterwards, Compound C (an AMPK activator) was added. CISD1 expressions in entorhinal cortex, hippocampus, temporal cortex, and frontal cortex tissues were decreased in AD patients versus controls via AlzData public database analysis. CISD1 expression was also downregulated in AD cellular models versus control cells. Interestingly, cell viability and SLC7A11 and GPX4 expressions were lower, but ROS and Fe2+ levels were higher in AD cellular models versus control cells, indicating an enhanced neuronal ferroptosis in AD. Subsequently, CISD1 overexpression plasmids raised cell viability and SLC7A11 and GPX4 expressions, while decreased ROS and Fe2+ levels compared with NC overexpression plasmids in AD cellular models. CISD1 overexpression plasmids also facilitated the phosphorylation of AMPK to activate this pathway compared to NC overexpression plasmids. Moreover, the addition of Compound C not only promoted the neuronal ferroptosis, but also attenuated the effect of CISD1 overexpression plasmids on regulating neuronal ferroptosis compared with the absence of Compound C in AD cellular models. Collectively, CISD1 represses neuronal ferroptosis by activating the AMPK pathway in AD cellular models, shedding a light on its potential engagement in the AD pathogenesis.

BACKGROUND:Anxiety is a common psychiatric comorbidity in epilepsy and is associated with adverse clinical outcomes. Emerging evidence suggests that inflammatory processes may contribute to its pathophysiology; however, the relationship between peripheral and central inflammatory markers and anxiety in epilepsy remains unclear. METHODS:This retrospective study included 184 patients with epilepsy, classified into those with anxiety symptoms (EP-A, n = 107) and without anxiety (EP-nA, n = 77) based on the Hamilton Anxiety Rating Scale. Clinical data and inflammatory markers from peripheral blood and cerebrospinal fluid (CSF) were collected. Logistic regression, restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) curves were used to identify independent risk factors and evaluate predictive performance. RESULTS:Patients with anxiety symptoms exhibited significantly elevated peripheral inflammatory markers, including platelet count, monocyte count, CRP, CAR, and PLR (all P < 0.05), as well as increased central markers such as CSF white blood cell count, lactate, and IgG index (all P < 0.05). Multivariate analysis identified CAR, PLR, CSF lactate, and IgG index as independent risk factors. RCS analysis demonstrated nonlinear associations for several markers, with risk increasing sharply beyond specific thresholds. The combined model showed good predictive performance (AUC = 0.814), with satisfactory sensitivity and specificity. CONCLUSIONS:Peripheral and central inflammatory markers are associated with anxiety in epilepsy. A combined biomarker model may provide a clinically useful tool for early risk stratification and supports a potential role of neuroinflammation in epilepsy-related anxiety.

OBJECTIVE:Juvenile myoclonic epilepsy (JME) is associated with large-scale brain network dysfunction. This study aims to investigate how anti-seizure medication (ASM) treatment alters resting-state functional networks in JME patients through resting-state EEG microstate analysis. METHODS:Ninety-six subjects participated in this study: 24 healthy controls (HC), 29 newly diagnosed JME patients who had not started ASMs therapy (JME-NM), and 43 JME patients on ASMs treatment with effective seizure control (JME-M). EEG data were collected for 10 min while participants were awake and resting with their eyes closed, using a standard 19-channel recording system. EEG topographies were categorized into four microstate classes (A, B, C, D), and parameters such as mean duration, occurrence rate, time coverage, and transition probabilities between microstates were computed and compared among the three groups. Advanced statistical methods were employed to ensure the robustness and validity of the findings. RESULTS:Significant alterations in EEG microstate characteristics were observed in untreated JME patients (JME-NM) compared to both healthy controls and treated patients. Microstate B had a markedly reduced mean duration in the JME-NM group, while microstate A displayed an increased occurrence rate and greater time coverage. Transition probabilities between specific microstates, such as from A to C, A to D, and B to C, were also significantly different in the JME-NM group. The normalization of these parameters in the JME-M group suggests that ASMs effectively stabilize altered brain networks, potentially mitigating the pathophysiological disruptions associated with JME. CONCLUSION:This study demonstrates that ASMs effectively normalize disruptions in sensory-motor and visual networks in JME patients. EEG microstate analysis provides a dynamic view of brain network alterations and offers potential as a biomarker for the diagnosis and monitoring of JME, as well as for evaluating treatment response. These findings advance our understanding of the neurophysiological mechanisms underlying JME.

This study aims to develop an exploratory classification model for Juvenile Myoclonic Epilepsy (JME) based on electroencephalogram (EEG) microstate features to assist clinical diagnosis and reduce misdiagnosis rates. A total of 123 participants were included in this study, consisting of 74 patients diagnosed with JME and 49 patients with Frontal Lobe Epilepsy (FLE). Resting-state EEG data were retrospectively collected from all participants. After preprocessing, microstate analysis was performed, and 24 microstate features (including duration, occurrence rate, coverage, and transition probability) were extracted and analyzed. Finally, the extracted microstate parameters were used to train six machine learning classifiers to distinguish between the two types of epilepsy. The performance of these models was assessed by calculating accuracy, precision, recall, F1 score, and area under the curve (AUC). The study found that all parameters of microstate A showed high consistency between the two groups. However, the JME group exhibited lower occurrence and smaller coverage of microstate B compared to the FLE group, while showing longer durations for microstate C. Additionally, the transition probabilities from microstate B to C and D were lower in the JME group, while the transition probability from C to D was significantly higher. When EEG microstate features were integrated into the six machine learning classifiers, the linear discriminant analysis (LDA) algorithm achieved the best classification performance (accuracy of 76.4

Fatal familial insomnia (FFI) is a rare autosomal dominant neurodegenerative disorder characterized by rapidly progressive dementia, severe sleep disturbances, and autonomic dysfunction. The clinical manifestations of FFI can exhibit substantial variations, making it crucial to rule out other conditions, such as autoimmune encephalitis and Creutzfeldt-Jakob disease, during early diagnosis. In this study, we describe the case of a 58-year-old man who experienced persistent insomnia, autonomic symptoms, gait instability, and rapidly progressive dementia. Polysomnography revealed considerable alterations brain positron emission tomography/computed tomography showed no significant abnormal changes and cerebrospinal fluid analysis indicated a slight elevation in protein levels. Results of tests for autoimmune encephalitis antibodies were negative. The presence of the prion protein gene D178N mutation was confirmed through genetic testing and in conjunction with the patient's clinical manifestations, a diagnosis of FFI was established. Owing to severe autonomic neuropathy and intractable hyponatremia resulting from excessive sweating, therapeutic interventions, including thoracic sympathetic nerve thermocoagulation and stellate ganglion block, were attempted. These treatments initially led to symptomatic improvements, such as reduced sweating and amelioration of hyponatremia; however, sweating persisted, albeit to a lesser extent. Despite these interventions, the patient's condition deteriorated, leading to death 16 months after symptom onset owing to progressive agrypnia excitata, worsening dementia, and gait instability. This case underscores the current lack of effective treatments for FFI and highlights the urgent need for further research on this debilitating disorder.

BACKGROUND:The aim was to develop an attention-based model using 18F-fluorodeoxyglucose (18F-FDG) PET imaging to differentiate autoimmune encephalitis (AE) patients from controls and to discriminate among different AE subtypes. METHODS:This multi-center retrospective study enrolled 390 participants: 222 definite AE patients (comprising four subtypes: LGI1-AE, NMDAR-AE, GABAB-AE, GAD65-AE), 122 age- and sex-matched healthy controls, and 33 age- and sex-matched antibody-negative AE patients along with 13 age- and sex-matched viral encephalitis patients, both serving as disease controls. An attention-based multi-instance learning (MIL) model was trained using data from one hospital and underwent external validation with data from other institutions. Additionally, a multi-modal MIL (m-MIL) model integrating imaging features, age, and sex parameters was evaluated alongside logistic regression (LR) and random forest (RF) models for comparative analysis. RESULTS:The attention-based m-MIL model outperformed classical algorithms (LR, RF) and single-modal MIL in AE vs. all controls binary classification, achieving the highest accuracy (84.00% internal, 67.38% external) and sensitivity (90.91% internal, 71.19% external). For multiclass AE subtype classification, the MIL-based model achieved 95.05% (internal) and 77.97% (external) accuracy. Heatmap analysis revealed that NMDAR-AE involved broader brain regions, including the medial temporal lobe (MTL) and basal ganglia (BG), whereas LGI1-AE and GABAB-AE showed focal attention on the MTL and BG. In contrast, GAD65-AE demonstrated concentrated attention exclusively in the MTL. CONCLUSION:The m-MIL model effectively discriminates AE patients from controls and enables subtyping of different AE subtypes, offering a valuable diagnostic tool for the clinical assessment and classification of AE.

PURPOSE:To provide consensus-based recommendations for the use of sodium channel blockers (SCBs) in the management of focal epilepsy. METHODS:A three-round modified Delphi procedure was conducted among a Delphi panel of 24 Chinese experts to build a consensus. A steering committee developed 9 statements related to SCBs for the treatment of focal epilepsy, and these statements were evaluated and voted upon by the expert panel. RESULTS:The expert panel achieved consensus on nine statements regarding the treatment recommendations for oxcarbazepine, lamotrigine, lacosamide, eslicarbazepine, topiramate, zonisamide and cenobamate in focal epilepsy patients and treatment adjustments for SCBs. CONCLUSION:This is a Chinese expert consensus on the use of SCBs in focal epilepsy developed using the modified Delphi method. These recommendations can help clinicians in their practice and guide future research.

OBJECTIVE:Ofatumumab presents a potentially promising alternative to current second-line immunotherapy for refractory anti-N-methyl-D-aspartate receptor autoimmune encephalitis (NMDAR-AE). We aimed to evaluate the efficacy and safety of ofatumumab as a novel second-line immunotherapy for NMDAR-AE. METHODS:This prospective, multicenter, nested cohort study compared patients with NMDAR-AE from the CHina Autoimmune encephalitiS outcomE study registry (CHASE) recruited between October 2011 and February 2024, treated with and without ofatumumab. The primary outcome was the proportion reaching a favorable functional outcome (modified Rankin Scale [mRS] score ≤2) at the last follow-up. Secondary outcomes included mRS scores and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores over the first 24-month follow-up and the proportion with further mRS score improvement after ofatumumab initiation. A propensity score matching was performed to balance major confounders. RESULTS:A total of 715 patients with AE were screened. Fifty-eight propensity score-matched patients with NMDAR-AE each in the ofatumumab group and non-ofatumumab group were analyzed. Fifty-four patients (93.1%) in the ofatumumab group achieved further mRS score improvement with a median time of 14 days from ofatumumab initiation, and 53 (91.4%) reached a favorable functional outcome at the last follow-up. For those who failed first-line immunotherapy, the ofatumumab group demonstrated a faster mRS score and CASE score improvement and more frequently reached a favorable functional outcome at the last follow-up compared with the non-ofatumumab group (87.9% vs. 64.7%, odds ratio [OR] 3.95; 95% confidence interval [CI] 1.12-13.94; p = 0.026). No serious adverse events associated with ofatumumab treatment were reported. INTERPRETATION:Ofatumumab showed substantial efficacy and safety, particularly in patients who failed first-line immunotherapy, warranting its consideration in NMDAR-AE management. ANN NEUROL 2025;98:80-92.

Hippocampal sclerosis (HS) is a pathological condition characterized by significant loss of hippocampal neurons and gliosis. This condition represents the most common neuropathological change observed in patients with temporal lobe epilepsy (TLE) and is also found in aging individuals. TLE related to HS is the most prevalent type of drug-resistant epilepsy in adults, and its underlying mechanisms are not yet fully understood. Therefore, developing improved methods for predicting and treating drug-resistant patients with TLE-HS is crucial. Patients with TLE-HS often experience cognitive impairment and psychological comorbidities, significantly affecting their quality of life. Consequently, a thorough review of the current research status of TLE-HS is essential, focusing on its prediction, diagnosis, treatment, and underlying mechanisms. The hippocampus plays a pivotal role in memory and cognition. HS of aging (HS-Aging), a condition linked to dementia in the ultra-elderly, is marked by severe CA1 (cornu ammonis) neuronal loss and frequent transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy, often misdiagnosed as Alzheimer's disease (AD). Nonetheless, clinical characteristics and patterns of hippocampal atrophy can help differentiate between the two disorders. This review aims to provide a comprehensive overview of the pathological features of HS, the relevant mechanisms underlying TLE-HS and HS-Aging, current imaging diagnostic techniques, including machine learning, and available treatment modalities. It also explores the prognosis and comorbidities related to these conditions. Future research directions include establishing animal models to clarify the poorly understood mechanisms underlying HS, particularly those related to emotional processing. Investigating post-HS behavioral and cognitive changes in these models will lay the foundation for further advancements in this field. This review is a cornerstone for future investigations and suggests additional research endeavors.

Ribosome-binding protein 1 (RRBP1) regulates ribosome assembly and stability to modify several important biological processes such as mitochondrial function, stress, cell differentiation, immunity, and axonal structure. This study aimed to investigate RRBP1 inhibition on microglial polarization and inflammation, and its mediated neuronal loss and oxidative stress in Alzheimer's disease (AD). Mouse microglia (BV-2), mouse hippocampal neuron (HT-22), human microglia (HMC3), and human neuroblastoma (SH-SY5Y) cell lines were cultured. A classical culture system containing BV-2 and HT-22, as well as HMC3 and SH-SY5Y, under β-amyloid treatment was applied to mimic AD cellular models. RRBP1 siRNA and control siRNA were transfected into BV-2 and HMC3 cells with no transfection as normal control; moreover, the ERK pathway was inactivated by PD98059 reagent. Microglial M1 phonotype marker (iNOS) and inflammatory cytokines (TNF-α and IL-1β levels) were decreased, while microglial M2 phonotype marker (ARG1) and pERK/ERK were increased by RRBP1 inhibition in BV-2 and HMC3 cells. Then microglial RRBP1 inhibition further elevated cell viability and superoxide dismutase (SOD), while reducing the cell apoptosis rate and reactive oxygen species (ROS) in HT-22 and SH-SY5Y cells. pERK/ERK was lowered after PD98059 treatment, which attenuated the effect of RRBP1 inhibition on microglial M1/M2 phenotypes and inflammatory cytokines in BV-2 and HMC3 cells, and further weakened the effect of microglial RRBP1 inhibition on cell viability, apoptosis rate, ROS, and SOD in HT-22 and SH-SY5Y cells. RRBP1 inhibition represses microglial M1 polarization and inflammation-mediated neuronal loss and oxidative stress by modifying the ERK pathway in AD.