Epilepsia最新文献

Objective: Temporal lobe epilepsy (TLE) is the most common focal epilepsy but remains highly heterogeneous across hemispheric and structural etiology. This study aimed to characterize microstate-based network dynamics in TLE and evaluate their diagnostic value for seizure lateralization and structural etiology using machine learning.

Methods: Resting-state electroencephalography (EEG) recordings from 150 patients with unilateral TLE (71 right, 79 left) and 65 healthy controls (HCs) were analyzed. EEG signals were segmented into canonical microstates (A, B, C, D), and microstate-specific spatial, and temporal dynamic functional connectivity (dFC) variability metrics were extracted using phase lag index analysis. After two-step feature selection, the appropriate number of features were derived and input into Random Forest, XGBoost, and Support Vector Machine (SVM) classifiers to distinguish: TLE vs HCs, left vs right TLE, and magnetic resonance imaging (MRI)-negative (MRI-neg) vs hippocampal sclerosis (HS) TLE subtypes (TLE-HS). Model performance was evaluated on independent hold-out validation set using receiver operating characteristic analyses.

Results: Compared with HCs, patients with TLE exhibited increased duration and occurrence of microstate D and reduced expression microstate B, reflecting maladaptive attentional overactivation and visual suppression. Spatial variability was globally decreased, most prominently in left TLE. SVM achieved excellent performance for TLE detection (area under the curve [AUC] = .98) and lateralization (AUC = .97), whereas classification between MRI-neg TLE and TLE-HS was limited (AUC = .58).

Significance: EEG microstate-derived dFC metrics provide reliable, non-invasive biomarkers for identifying and lateralizing TLE using short duration resting-state EEG recordings. This framework advances understanding of TLE heterogeneity and supports the development of individualized electrophysiological tools for precision diagnosis.

Hydroxycarboxylic acid receptor 1 (HCAR1) is a G-protein-coupled lactate receptor expressed in the brain and plays a role in neuronal excitability and repair after injury. Hypoxic-ischemic encephalopathy (HIE) is the most common cause of brain injury and seizures in term neonates. The goal of this study was to describe HCAR1 expression and function in the neonatal brain and understand its role in HIE-associated seizures. HCAR1 expression was measured using quantitative reverse transcriptase polymerase chain reaction in postnatal day (p)10-50 mice. Neuronal properties and spontaneous excitatory postsynaptic currents (sEPSCs) were measured in hippocampal principal neurons from HCAR1 knockout and wild-type mice when exposed to lactate. p10 HCAR1 knockout and wild-type mice were exposed to hypoxia-ischemia (HI) and underwent electroencephalography to compare seizure burden. HCAR1 was expressed at p10 at similar levels to adults. Lactate decreased amplitudes and sEPSC frequency in wild-type but not HCAR1 knockout mice. After HI, HCAR1 knockout mice had higher seizure burden and behavioral seizure scores than wild-type mice. HCAR1 is expressed on neurons and plays a role in neuronal excitability and seizures in the neonatal brain.

Objective: Surgical resection for epilepsy seeks to maximize seizure freedom while minimizing new neurocognitive impairments. Tailored resections guided by anatomoelectroclinical (AEC) hypotheses offer the possibility of sparing parts of the hippocampus. The relationship between the extent of hippocampal resection and postoperative neurocognitive outcomes in this context has not been studied and has important implications for clinical practice. We test this relationship in a series of left and right tailored anterior temporal lobectomy (ATL) surgeries.

Methods: We conducted a retrospective analysis of 34 adult patients with drug-resistant temporal lobe epilepsy (18 left, 16 right) who underwent tailored ATL based on individualized AEC hypotheses at the University of Pittsburgh Medical Center. All patients completed standardized pre- and postoperative neuropsychological testing, and 85.3% underwent preoperative stereoelectroencephalography to guide resection. Surgical extent was tailored through a multidisciplinary process integrating AEC correlations and intraoperative electrophysiology. Preoperative and postoperative hippocampal volumes were measured and correlated with changes in verbal and visual memory, as well as language performance.

Results: Greater extent of resection of the left hippocampus was significantly associated with worse postoperative outcomes in both verbal and visual recall. Extent of resection of the right hippocampus was not related to reductions in performance across any domain, with some indication of improvements in performance after right ATL surgery at the group level. Seizure outcomes (66.6% Engel I at 2 years) were consistent with the existing literature and did not vary with hippocampal resection extent.

Significance: These findings highlight the critical role of the left hippocampus in supporting both verbal and visual memory and underscore the importance of preserving hippocampal tissue during left ATL when feasible. Our results support the utility of AEC-guided tailored resections as a strategy to balance seizure control with cognitive preservation.

Objective: Interictal epileptiform discharges (IEDs) are transients observed on the electroencephalogram (EEG) of patients with epilepsy. IEDs have traditionally been recorded from scalp or intracranial EEG macrocontacts, which coarsely sample neural activity. Here, we investigated the use of flexible, high-resolution microelectrocorticographic (μECoG) arrays for measuring IEDs with greater spatiotemporal precision to test whether there exist microscale patterns of IED activity that may be missed on standard intracranial EEG.

Methods: We used liquid crystal polymer thin-film μECoG arrays with both high resolution (.76-1.72-mm spacing, 200-μm diameter) and large cortical coverage (144-1596 mm²) to record from seven patients undergoing surgical treatment of epilepsy. We identified IEDs by a combination of expert review and automated detection. We quantified the spatial extent of IEDs, mapped patterns of repeated IED activity, and quantified IED propagation direction using multilinear fit models. We also compared IED detection rates and propagation measurements between μECoG arrays and simulated macroarrays (10-mm spacing, 2.3-mm diameter).

Results: We demonstrated successful use of μECoG arrays to map intraoperative microscale patterns of IEDs. The majority of patients (5/7) exhibited elevated IED activity that was highly localized (subcentimeter localization). Across all patients, 40% of detected IEDs were observed within a 4-mm radius of cortex. μECoG arrays also mapped the direction of IED propagation. An average of 39% (range = 4.2%-96.5%, SD = ±36.8%) of the IED events captured by the μECoG arrays were not detectable by simulated macrocontacts.

Significance: These intraoperative data demonstrate that μECoG arrays can map the microscale spatiotemporal activity of IEDs. These patterns of IEDs may be poorly captured by standard, macroscale recording devices. Our findings support the use of high-resolution, large area coverage μECoG arrays for the presurgical and intraoperative mapping of epileptic cortex.

Objective: Epilepsy carries an increased risk of premature mortality. Although seizure freedom may reduce deaths, most population-based evidence originates from high-income countries. Data from low-income settings, such as rural China, remain scarce. We update mortality patterns and evaluate their associations with achieving 1-year seizure freedom among rural populations in China.

Methods: People with epilepsy living in rural Henan, China, were enrolled between 2010 and 2011 and followed up at three subsequent time points over 10 years. We collected demographic and clinical data, including survival outcomes. Seizure freedom was defined as a 12-month seizure-free interval recorded in any follow-up period. Causes of death were assessed using a structured verbal autopsy questionnaire and adjudicated by a multidisciplinary panel. We estimated mortality rates, standardized mortality ratios (SMRs), and cause-specific distributions, and used regression models to identify mortality predictors and associations with seizure freedom.

Results: Among the 610 participants enrolled (57.5% male), 67 had died over 10-year follow-up, yielding an all-cause mortality rate of 13.5/1000 person-years (95% confidence interval [CI] = 10.5-17.2) and an age- and sex-adjusted SMR of 2.4 (95% CI = 2.3-2.5). Epilepsy-related deaths accounted for 48% of deaths, with sudden unexpected death in epilepsy being predominant (33%). People who had ever achieved 12-month seizure freedom (n = 317) had significantly lower SMRs than those who never did (n = 293). Ever achieving seizure freedom was independently associated with a lower risk of all-cause mortality (odds ratio [OR] = .30, 95% CI = .17-.52) and epilepsy-related death (OR = .29, 95% CI = .12-.63). This protective effect was most pronounced in women, older adults, those with seizure onset during adulthood, and those without comorbidities.

Significance: Mortality in this cohort remains more than twice that of the general population, with sudden death accounting for one third of cases. Achieving 1-year seizure freedom even once during follow-up substantially reduced mortality risk and altered cause-of-death distributions. This finding underscores seizure control as a practical and encouraging treatment goal in resource-limited settings.

Objective: This study was undertaken to present the results of an exploratory phase 2 trial of stiripentol in Lennox-Gastaut syndrome (LGS).

Methods: This exploratory single-blind, single-arm, nonrandomized sequential-period phase 2 study was conducted at four centers in France between January 1989 and August 1993. Eligible patients were aged 2-20 years with LGS and experienced at least one seizure per week despite optimized therapy. After a 1-month baseline period under a stable treatment regimen, patients received placebo for 1 month followed by stiripentol for 2 months.

Results: Sixteen patients with LGS were enrolled, and efficacy was assessable in 14. The median [Q1-Q3] overall seizure frequency decreased from 31 [16-89] at baseline to 14 [8-21] after the first month of stiripentol (p = .044) and further to 4 [0-18] after the second month (p = .044). The reduction was consistent across seizure types. Eight patients (57%) were responders (≥50% reduction in overall seizure frequency) at the end of stiripentol treatment, including five (36%) who achieved complete seizure freedom and two with a ≥75% reduction in seizure frequency. All patients reported at least one adverse event during stiripentol treatment, most commonly somnolence, decreased appetite, and vomiting. These effects may be related to the high stiripentol doses administered (median = 91 mg/kg/day in the second month). Despite their frequency, no serious adverse events were reported during the stiripentol treatment period, and no clinically meaningful changes in hematological parameters or liver enzyme levels were observed.

Significance: Although this study was conducted before standardized clinical trial designs for LGS were established, a more comprehensive evaluation of stiripentol could have provided further insight into its potential benefits in this severe developmental and epileptic encephalopathy.

The term consciousness has been reintroduced in the updated seizure classification. Concerns have been raised that "ictal impaired consciousness" may be misunderstood by persons with epilepsy (PWEs) and their caregivers, particularly that English-speaking individuals might equate it with complete loss of consciousness. We conducted an online survey distributed via epilepsy organizations and social media to assess whether English-speaking PWEs and caregivers could understand and apply a simple medical definition of consciousness: "In medical terms, consciousness means being able to remember things and respond to what is happening around you. During a seizure, consciousness is considered affected if the person cannot remember what happened and if they are unable to respond normally when people try to interact with them." The survey was completed by 253 respondents (148 caregivers, 105 PWEs). Almost all participants (97%) found the definition clear, 90% reported they could apply it to their seizures, and 99% demonstrated comprehension by correctly interpreting an example question. No significant differences were observed between PWEs and caregivers, across education levels, or by seizure characteristics. These findings indicate that PWEs and caregivers can readily understand and apply the concept of ictal impairment of consciousness when given a concise, patient-friendly definition.

Objective: Sudden unexpected death in epilepsy (SUDEP) is linked to respiratory and autonomic failure with post-ictal periods of prolonged hypercapnia indicative of impaired central chemoreception. Yet how interictal hypercapnic cardioventilatory responses vary by seizure phenotype is unclear. We aimed to determine whether central chemoreception and autonomic regulation differ across epilepsy phenotypes during a standardized CO₂ challenge. We hypothesized that rats with chronic generalized tonic-clonic seizures would show impaired hypercapnic cardioventilatory and autonomic responses compared with rats with generalized absence seizures and healthy controls.

Methods: We measured breathing frequency (f_B), heart rate (HR), and heart rate variability (HRV) before, during, and after a 1 h 10% CO₂ exposure in three groups of male rats: kainic acid (KA; tonic-clonic), genetic absence epilepsy rat from Strasbourg (GAERS; absence), and Wistar controls.

Results: Controls showed increased f_B and decreased HR during hypercapnia. KA rats exhibited blunted f_B and HR responses; GAERS displayed preserved f_B elevation with faster post-challenge normalization and intermediate HR changes. Coupling of f_B and HR collapsed during CO₂ in both epilepsy groups and re-emerged in recovery. In KA rats, Stage 3-4 seizure burden positively correlated with HR during hypercapnia. HRV reactivity to hypercapnia was robust in controls, attenuated in GAERS, and largely absent in KA, whereas interictal baseline HRV did not differ among the groups.

Significance: These data support seizure-type-specific disruption of chemoreflex-autonomic integration. Extending clinical hypercapnic ventilatory response (HCVR) testing, a hypercapnic cardioventilatory response (HCCVR), that is, a combined f_B, HR, and HRV readout, may help to refine SUDEP risk stratification beyond seizure frequency and type.

Objective: Tapering of the antiseizure medication dosage in the epilepsy monitoring unit can provoke seizures, but its effects on seizure dynamics remain poorly characterized. This study addresses three questions: (1) Does antiseizure medication tapering influence spatiotemporal dynamics of seizures? (2) Does the tapering rate affect these dynamics? (3) Does tapering have a similar effect on interictal epileptic discharges as it does on seizures?

Methods: Patients with drug-resistant epilepsy undergoing stereoelectroencephalographic (stereo-EEG) presurgical evaluations at Duke University Medical Center (n = 104) and the Montreal Neurological Institute and Hospital (n = 80) were screened. We included patients in whom the antiseizure medication dosage was tapered from the highest daily dosage (high dosage) to ≤ 50% (low dosage) during stereo-EEG monitoring, and at least one seizure from the same focus was recorded in both conditions. Using an intrapatient design, we compared seizure onset-zone, onset pattern, and propagation dynamics between the two conditions. Given the intrinsic seizure variability, comparisons were made between same-dosage and cross-dosage seizure pairs. We further assessed effects of tapering rates and examined the characteristics of interictal epileptiform discharges.

Results: Among 30 patients, the proportion of channels in the seizure onset zone did not differ between high-dosage and low-dosage conditions (7.25% vs. 8.95%, p = .50, d = -.04). Similarly, no differences were observed in the overlap ratio of seizure-onset regions (62% vs. 64%, p = .72, d = -.01), or the cross-correlation of seizure-onset patterns (.36 vs. .35, p = .54, d = .04) when comparing same-dosage versus cross-dosage seizure pairs. Conversely, seizures at low dosage involved more channels (40.71% vs. 81.49%, p = .001, d = -.39) and lasted longer (33.36 s vs. 74.30 s, p < .01, d = -.47). Tapering rate did not affect seizure dynamics. The mean interictal epileptiform discharge rate and number of propagation channels also remained unchanged.

Significance: Despite seizure exacerbation during antiseizure medication tapering, seizure-onset location remained stable. This supports the robustness of seizure-based localization even under reduced medication levels and rapid tapering regimens.