Dong Zhou

Background: Effective seizure management in pregnant women with epilepsy poses significant clinical challenges. This study aimed to investigate the pharmacokinetic changes of second-generation antiseizure medications (ASMs) and their association with the deterioration of seizure control in Han Chinese women with epilepsy. Methods: Patient clinical data including oral daily doses and seizure frequency were acquired from routine clinical practice. Blood concentrations of ASMs determined by therapeutic drug monitoring (TDM) were used to calculate apparent oral clearance (CL) at preconception and each trimester during pregnancy. The ratio of ASM concentration in each trimester to the preconception baseline concentration (RTC) was compared between patients experiencing seizure deterioration and those maintaining stability. Moreover, receiver operating characteristic (ROC) curve analysis was used to identify the threshold RTC value predicting increased seizure frequency. Results: A total of 52 pregnant patients with epilepsy were initially enrolled in this study. The apparent oral clearance of levetiracetam (LEV) and lamotrigine (LTG) showed a significant increase across all trimesters compared to the nonpregnant baseline. Peak clearance occurred in the third trimester for LTG with a 2.0-fold relative clearance ( P < 0.05). Similarly, LEV displayed maximum apparent oral clearance increase during the third trimester, reaching 1.6 folds of baseline value ( P < 0.05). As a result, serum concentrations of LEV and LTG significantly decreased during pregnancy compared to non-pregnant baseline levels ( P < 0.05). However, the apparent oral clearance and the blood level of oxcarbazepine (OXC) remained stable throughout gestation compared to the preconception baseline. Moreover, the RTC values significantly differed between participants with and without seizure deterioration for all three ASMs, indicating that lower RTCs were associated with seizure worsening. Conclusions: Our study revealed significant pharmacokinetic fluctuations of LEV and LTG in Chinese pregnant women. This highlights the necessity of early therapeutic drug monitoring for newer ASMs and dose adjustments to maintain blood concentrations near the non-pregnant baseline level in pregnant women with epilepsy.

Anti‐ N‐methyl‐D‐aspartate receptor encephalitis (NMDAR‐E) is a prevalent autoimmune neurological disorder, yet T cell‐driven immunopathology and its contributions to therapeutic resistance and fulminant neuroinflammation remain poorly defined. Integrative single‐cell multi‐omic profiling, combining single‐cell RNA sequencing, single‐cell T cell receptor (TCR) sequencing, and cellular indexing of transcriptomes and epitopes by sequencing, is applied to systematically map peripheral and cerebrospinal fluid (CSF) immune landscapes in treatment‐naïve NMDAR‐E patients, with orthogonal validation conducted across independent cohorts via multiparameter flow cytometry and ex vivo NR1 peptide stimulation. Clonally expanded CX3CR1‐expressing CD4 ⁺ and CD8 ⁺ T cells are identified as a core disease‐associated effector population, characterized by high predicted affinity for the pathogenic GluN1 N368/G369 epitope, robust proinflammatory and cytotoxic transcriptional programs, and enhanced intercellular crosstalk with activated B cells through major histocompatibility complex (MHC), CD99, and macrophage migration inhibitory factor signaling axes. Preferentially enriched in patient CSF, these cells produce elevated interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) upon antigen‐specific stimulation, collectively highlighting a disease‐associated inflammatory T cell state linked to peripheral immune activation and CNS immune remodeling, with potential translational relevance for future biomarker and therapeutic investigation.

Objective: Epilepsy is associated with increased risk of excess mortality compared to the general population. Identifying causes of death is critical for guiding prevention strategies. Earlier studies in resource‐limited settings suggested that accidental deaths were the main causes, but whether the mortality pattern has changed over time remains unclear. This study aimed to update the knowledge on mortality and causes of death of people with epilepsy in rural China. Methods: In this nationwide cohort study, we analyzed data from the Epilepsy Prevention and Management Project in rural China between January 1, 2018, and December 31, 2020. Mortality outcomes included all‐cause mortality, causes of death, and standardized mortality ratios (SMRs). Kaplan–Meier, multivariable Cox, and restricted cubic spline analyses were used to assess mortality risk and associated factors. Results: Among 17 515 participants followed for 25 922 person‐years, 381 deaths were recorded, yielding an all‐cause mortality rate of 14.7 per 1000 person‐years. The leading causes of death were circulatory system diseases (47.8%), including cerebrovascular disease (28.9%), and heart disease (18.9%). The all‐cause SMR was 3.51 (95% confidence interval = 3.33–3.70). The highest cause‐specific excess mortality was observed for brain malignancies (SMR = 20.30). Male sex, older age at epilepsy onset, longer disease duration, and higher baseline seizure frequency were independently associated with mortality. Significance: People with epilepsy in rural China continue to experience substantial and potentially preventable excess mortality. As mortality patterns shift, prevention strategies should extend beyond seizure control and injury prevention to include vascular risk management and timely neuroimaging for suspected structural lesions. Prospective studies are needed to determine whether these strategies improve survival.

Objective: This study was undertaken to assess long‐term efficacy, safety, and tolerability of adjunctive cenobamate in an open‐label extension (OLE) of a randomized, double‐blind, placebo‐controlled, dose–response study (NCT04557085; YKP3089C035 [Study C035]) in Asian patients with uncontrolled focal seizures. Methods: Patients 18–70 years old with uncontrolled focal seizures despite treatment with 1–3 antiseizure medications who completed the 24‐week double‐blind treatment period ( n = 425) at cenobamate doses of 100, 200, or 400 mg/day or placebo could enter a 52‐week OLE. All patients were converted to a cenobamate dose of 400 mg/day during a 20‐week double‐blind conversion phase and then entered a 32‐week open‐label maintenance phase at a starting dose of 300 mg/day. Results: Among the 410 patients who entered the double‐blind conversion phase, 357 (263 and 94 originally randomized to cenobamate and placebo, respectively) entered the OLE maintenance phase. The median percent focal seizure frequency reduction from double‐blind baseline for patients who received at least one dose of cenobamate during the 32‐week maintenance phase was 83.6%. The percent of patients achieving ≥50% and 100% responses during the maintenance phase was 75.1% and 25.5%, respectively. Among patients entering the OLE, 84.6% (347/410) completed the 52 weeks of treatment with cenobamate. The most commonly occurring treatment‐emergent adverse events (TEAEs) during the entire OLE were dizziness, somnolence, γ‐glutamyl transferase (GGT) increase, and COVID‐19 infection. GGT increase was not associated with any clinically significant findings. Serious TEAEs occurred in 11.7% of patients (48/410). There were no deaths and no cases of DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome reported. Significance: The high long‐term seizure frequency reductions, including a 100% responder rate of 25.5%, were consistent with previous long‐term cenobamate efficacy. The OLE safety profile was also generally consistent with the known cenobamate safety profile, with no new safety signals identified. These results support the use of cenobamate in adult Asian patients with uncontrolled focal seizures.

Surgical failure in temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS) may reflect insufficient disruption of epileptogenic networks. We investigated whether integrating quantitative spatial patterns of regional atrophy and hypometabolism, along with clinical features, could provide complementary prognostic information for postoperative seizure freedom. T1‐weighted MRI, ¹⁸ F‐FDG‐PET, and postoperative CT scans of patients with TLE‐HS were retrospectively analyzed against a validated healthy control cohort to compute age‐ and gender‐adjusted W ‐score maps. Regional relationships of atrophy and hypometabolism were assessed using bivariate correlations and multiple regression analyses. Machine learning models integrating laterality of seizure onset, preoperative (extra‐)temporal atrophy/hypometabolism extent, seizure frequency, focal to bilateral tonic–clonic seizures during the preceding year, and resection volume were developed to predict seizure freedom 1 year after surgery. Model interpretability was assessed via permutation‐based variable importance analysis. The cohort comprised 101 patients with TLE‐HS (48 left, LHS; 53 right, RHS), including 72 patients who underwent anterior temporal lobectomy. Distinct modality‐specific patterns emerged: hypometabolism was significantly greater than local atrophy in left temporo‐limbic cortex in TLE‐LHS, while atrophy exceeded hypometabolism in bilateral occipital regions in TLE‐RHS. Positive correlations between local atrophy and hypometabolism were more robust in ipsilateral temporo‐limbic cortex in TLE‐LHS. The combined model integrating preoperative atrophy and hypometabolism features (AUC: 0.56–0.64) significantly outperformed single‐modality models ( p _fdr < 0.05). Notably, incorporating clinical factors further enhanced predictive performance (AUC: 0.63–0.70) and model calibration. This comprehensive preoperative clinical‐imaging model achieved robust prognostic efficacy that was not significantly improved by the addition of actual postoperative resection volumes. Structural MRI and ¹⁸ F‐FDG‐PET reveal complementary facets of the epileptogenic network in TLE‐HS. While integrating multimodal imaging with clinical metrics demonstrates significant synergistic potential for predicting surgical outcomes, our models remain exploratory. External validation in independent multi‐center cohorts is required before translating these findings into precise clinical tools for surgical planning.

Narcolepsy and epilepsy are chronic neurological disorders that occasionally coexist. Overlapping symptoms, such as sudden loss of muscle tone and uncertainty regarding preservation of awareness, frequently complicate accurate diagnosis and ambiguity remains regarding optimal therapeutic strategies. To characterise the clinical features and treatment outcomes in individuals with comorbid narcolepsy and epilepsy, we described a 17-year-old girl with concomitant epilepsy and narcolepsy presented in our clinic. The overlapping symptomatology of narcolepsy and epilepsy can lead to significant diagnostic pitfalls, particularly when excessive daytime sleepiness is overlooked or attributed to external factors such as mental disorder or the side effects of antiseizure medications. Careful evaluation of clinical features, sleep studies and immunological markers through a multidisciplinary team approach is essential for accurate differentiation and optimal treatment. Prompted by this encounter, we additionally conducted a literature review and then synthesised ten reported cases of narcolepsy-epilepsy comorbidity, focusing on demographic profiles, diagnostic findings, treatment approaches and therapeutic outcomes. All ten published cases were diagnosed with narcolepsy type 1, predominantly with childhood or adolescent onset. EEG commonly showed 3–5 Hz generalised spike-and-wave discharges, and most individuals reported carrying the HLA-DQB1*06:02 allele. In more than 80% of cases, narcolepsy preceded or coincided with epilepsy, though diagnostic delays for narcolepsy were frequent. Both conditions generally responded well to combined standard treatments, such as pitolisant, sodium oxybate, lamotrigine and valproate, though antiseizure medications occasionally worsened sleepiness. This study underscores the diagnostic pitfalls associated to overlapping symptoms of narcolepsy and epilepsy and emphasises the value of multidisciplinary diagnostic collaboration for the timely recognition and effective management of these coexisting neurological disorders.