Epilepsia最新文献

Objective: This study was undertaken to determine whether bilateral independent or unclear (BI/U) scalp electroencephalographic (EEG) ictal onset patterns may predict the diagnostic yield of stereo-electroencephalography (SEEG) and inform surgical decision-making in patients with focal drug-resistant epilepsy.

Methods: We conducted a retrospective cohort study of consecutive patients with focal drug-resistant epilepsy and BI/U ictal onset on scalp EEG who underwent SEEG evaluation at our center between January 2012 and December 2024. All patients had undergone noninvasive and invasive presurgical assessments. Surgical outcomes were determined using the Engel classification following at least 1 year of postoperative follow-up. A blinded decision validation substudy was also performed, where the team made decisions regarding SEEG and surgical interventions when patients found to have a single SEEG seizure onset zone (SOZ) were presented. Responses were stratified to inform the added diagnostic value of SEEG.

Results: Of 255 SEEG cases screened, 84 patients (33%) had BI/U ictal onset on scalp EEG. The cohort was 56% female, with a median seizure onset age of 12 years (interquartile range = 6-20); 65.5% had temporal lobe epilepsy (TLE). A single SOZ was identified in 14.3% of cases (TLE: 14.5%, extratemporal: 13.8%). These patients had shorter SEEG recording durations (mean = 11 vs. 15.79 days in those with multifocal SEEG SOZs, p = .009). Curative focal resections were performed in 12% (n = 10), with long-term Engel I outcomes achieved in one patient of the entire cohort (1.2%). Palliative resections occurred in 26% (n = 22), with Engel I outcomes in 7% (n = 6). In 50% of the blinded cases, the epilepsy surgery team reported that they would not have recommended SEEG based on phase I data.

Significance: In patients with BI/U ictal onset on scalp EEG, the likelihood of identifying a single SEEG SOZ, and subsequently achieving seizure freedom, is low. Scalp EEG ictal onset patterns may aid in triaging candidates for invasive evaluation, informing patients regarding presumed SEEG outcome, and avoiding unnecessary surgical procedures.

Objective: Acute symptomatic seizures (ASyS) occur in up to 30% of patients with intracerebral hemorrhage (ICH) when continuous electroencephalography (cEEG) is used, potentially worsening outcomes. Identification of early EEG biomarkers of ASyS may help guide personalized antiseizure medication (ASM) prophylaxis. Here, we aimed to describe early interictal EEG patterns, their dynamics, and their association with seizure risk, considering the effect of prophylactic levetiracetam.

Methods: This prospective analysis used data from the PEACH phase 3 trial (2017-2020), which enrolled adults with acute spontaneous supratentorial ICH, randomized to receive levetiracetam or placebo. Patients underwent systematic 48-h cEEG within 48 h of symptom onset. Electrographic seizures and interictal EEG patterns were analyzed using standardized terminology of the American Clinical Neurophysiology Society. Associations between rhythmic and periodic patterns (RPPs) and seizures with clinical and radiological variables were assessed using univariate analyses. We also conducted exploratory testing of the CAV (cortical involvement, age < 65 years, volume > 10 mL) score for predicting ASyS, incorporating RPPs and ASM exposure.

Results: Forty-two patients were included (median [Q1-Q3] age = 72 [60-79] years, 29% women), 19 in the levetiracetam group. Interictal EEG abnormalities were common and not influenced by ASM, including background asymmetry (73%), sporadic epileptiform discharges (62%), and RPPs (52%). RPPs were associated with ICH volume (p = .039) and cortical involvement (p = .003). Among patients with RPPs, 50% developed ASyS (20% in those treated with ASM vs. 75% in untreated patients, p = .030). Most patients (91.7%) with seizures had RPPs that preceded seizures, in >90% cases by 12 (Q1-Q3 = 4-25) h. Integrating RPPs into the CAV model led to an improvement of ASyS prediction (area under the curve = .949 vs. .918, p = .53) that was statistically nonsignificant.

Significance: RPPs are strong markers of ictogenesis in acute ICH and precede ASyS, thus offering a potential therapeutic window. These findings support the use of early cEEG for risk stratification and personalized ASM prophylaxis.

Objective: Despite decades of development in anti-seizure medications, ~30% of individuals remain refractory to all treatments, and none of the existing therapies are disease modifying. Identifying targets outside the current preclinical paradigm is critically important. This study aimed to characterize the landscape of current epilepsy treatments at the level of gene interaction networks and identify novel genetic modifiers of epilepsy as potential novel therapeutic targets.

Methods: We performed a functional network analysis to score genes based on their interactions with known epilepsy genes, and we integrated these functional scores with population genetics data and drug tractability information. In parallel, we performed a meta-analysis of genome-wide association studies of epilepsy-related phenotypes in genetically diverse mice using a large compendium of historical phenotyping data. Genes within mapped loci were prioritized based on functional rankings, and genomic evolutionary rate profiling (GERP) was used to identify highly single-nucleotide polymorphisms at evolutionarily constrained positions.

Results: Functional network analyses of known epilepsy genes revealed a strong involvement of neurodevelopmental processes in epilepsy pathogenesis, which are not targeted by existing or emerging treatments. Meta-analysis of seizure traits in mice identified 118 non-overlapping loci harboring potential seizure phenotype modifiers. Using functional rankings, we prioritized 168 candidate genes within these loci and used GERP scores to filter down to 75 SNPs as candidate variants within these genes. Among them, five genes-Ephb2, En2, Cadps2, Igsf21, and Cep170-contain regulatory variants in evolutionarily constrained sites. Four of these genes are validated as modifiers of neurological traits, including epilepsy susceptibility.

Significance: This study prioritized epilepsy modifier genes that are strongly predicted to influence neurodevelopmental processes, which are underrepresented among current therapeutic targets. Furthermore, the identified genes represent novel candidate modifiers with potential clinical relevance. Our systems-level analysis offers a novel view into the potential target landscape, pointing toward promising new directions for disease-modifying treatments.

Objective: Precise localization of epileptogenic tissue is critical for successful surgery in drug-resistant temporal lobe epilepsy (TLE) but is challenging in those requiring intracranial electroencephalography (iEEG). A range of modalities are used for localization, including magnetic resonance imaging (MRI) and EEG, which are typically integrated qualitatively by the clinical team.

Methods: This study quantitatively performed retrospective analysis of three modalities in 40 individuals with TLE who underwent subsequent resective surgery: preoperative diffusion-weighted MRI, T1-weighted MRI, and iEEG. Brain abnormalities in gray matter (GM) volume, superficial white matter (SWM) mean diffusivity, and interictal iEEG band power were derived by comparison to 97 MRI controls and 247 subjects with iEEG. We hypothesized that combined abnormalities in GM and SWM could differentiate postsurgical outcomes and adding iEEG abnormalities would improve outcome differentiation.

Results: MRI (union of GM and SWM) abnormalities were primarily concentrated in the ipsilateral hippocampus and inferior temporal regions. Resection of these abnormal regions effectively differentiated seizure-free outcomes (area under the curve [AUC] = .76, area under the precision-recall curve [AUPRC] = .78, p < .01), corroborating previous results from larger TLE cohorts. Adding iEEG abnormalities improved outcome differentiation (AUC = .92, AUPRC = .89, p < .01; z = 2.01, p < .05). MRI abnormalities were more likely to colocalize with iEEG implantation sites (z = 6.26, p < .01) and iEEG abnormalities (z = 4.34, p < .01) in individuals with favorable outcomes (International League Against Epilepsy [ILAE] class 1 and 2), but not in those with less favorable outcomes (ILAE class 3+).

Significance: Combining quantitative MRI-derived GM and SWM abnormalities with interictal iEEG data improves localization of epileptogenic tissue and postsurgical outcome differentiation. Multimodal approaches may offer added value for surgical planning in complex situations.

Objective: Biallelic variants in TBC1D24 represent a rare cause of epilepsy and neurodevelopmental disorders, including severe developmental and epileptic encephalopathies. Here, we present the first attempt to delineate the longitudinal disease histories and effectiveness of antiseizure medications (ASMs) in TBC1D24-related disorders.

Methods: We performed an analysis of the electronic medical record data of 15 individuals with TBC1D24-related disorders. Using the Human Phenotype Ontology, we recorded neurological histories and medication responses across 197 patient-years of information.

Results: Individuals with TBC1D24-related disorders presented with a range of seizure types with a median age at seizure onset of 3 months-most frequently (73%) with focal myoclonic seizures both sparing and impairing consciousness. We report the maximum prevalence (MP) of various features as percentages of individuals reporting a given phenotype at that time point, compared to all those with available data at that time point. MP of focal seizures was at 6.25 and 7.75 years of age (88%), myoclonic seizures (focal and generalized) between 9 and 10 years of age (80%), and status epilepticus at 9 and 11 months of age (90%). Individuals also presented with a range of movement disorders. The MP of non-epileptic myoclonus was 100% at 1 and 17 months of age, tremor at 14 months of age (67%), ataxia at 7.25 years of age (45%), and episodic hemiplegia at 3.25 years of age (20%). The use of phenobarbital, oxcarbazepine, and topiramate showed the most promise in seizure management when compared to other ASMs. Everolimus, phenobarbital, and oxcarbazepine proved more effective in maintaining seizure freedom or reducing seizure frequencies in focal and myoclonic seizures compared to other ASMs.

Significance: TBC1D24-related disorders are characterized by severe and pharmacoresistant epilepsy, with status epilepticus, focal seizures, and myoclonic seizures early in life. This study offers novel insights into the longitudinal disease course and treatment response in TBC1D24-related disorders, a critical first step toward clinical trial readiness.

Objective: This study was undertaken to investigate the longitudinal volumetric changes of the contralateral hemisphere following hemispherotomy in patients with Sturge-Weber syndrome (SWS) and to evaluate their association with neurodevelopmental outcomes.

Methods: We retrospectively analyzed 33 pediatric patients with SWS who underwent hemispherotomy and had at least one follow-up magnetic resonance imaging (MRI) at 6, 12, or 24 months postoperatively. Cortical volume of the contralateral (nonsurgical) hemisphere was measured on 3-T MRI using SPM12 segmentation, and the volumetric increase rate was calculated. Associations between cortical volume and clinical factors, including age at surgery and seizure outcome, were examined using a linear mixed-effects model. We evaluated the relationships between the cortical volume of the contralateral hemisphere and the acquisition of neurodevelopmental milestones (standing, walking, single words, and sentences). Healthy age- and sex-matched controls (n = 22) were included for comparison.

Results: Contralateral cortical volume significantly increased over time following hemispherotomy (p < .01). Earlier hemispherotomy was associated with greater volumetric growth (p < .001), independent of patient age at postoperative MRI acquisition. Patients with larger age-adjusted cortical volumes exhibited earlier acquisition of standing and walking (ρ = -.70 and -.63, respectively). No significant correlation was observed between cortical hypertrophy and seizure outcome.

Significance: This study demonstrates that the contralateral hemisphere undergoes time-dependent hypertrophy following hemispherotomy in patients with SWS. Early hemispherotomy may enhance this structural plasticity and contribute to improved neurodevelopmental outcomes. Longitudinal volumetric analysis of the contralateral hemisphere may serve as a surrogate biomarker of structural reorganization and a valuable tool to guide the optimal timing of surgical intervention in this population.

Acute posthypoxic myoclonus (PHM) is a neurological complication that typically emerges within 12-48 h following cardiac arrest, often in comatose patients. It can present as generalized, multifocal, or focal myoclonus and has traditionally been associated with poor prognosis. There are currently no standardized guidelines for its management, and prognostic outcomes remain variable. This review synthesizes the available evidence on clinical features, pathophysiology, diagnostic approach, and treatment of acute PHM. We reviewed 21 studies on PHM. Most patients experienced poor outcomes, including high rates of mortality or progression to persistent vegetative state, although a minority achieved recovery. Treatment remains largely empirical and variable, with benzodiazepines and antiseizure medications (e.g., levetiracetam, valproate, clonazepam, perampanel) being commonly used. No therapeutic intervention has consistently demonstrated improved long-term neurological outcomes. We propose a possible treatment algorithm for PHM. Acute PHM is a clinically heterogeneous disorder with significant diagnostic and therapeutic challenges. Future research should focus on refining diagnostic criteria and identifying targeted therapies to improve outcomes in this often-fatal condition.

Objective: Posterior corpus callosotomy is an established palliative surgical option for patients with drug-resistant generalized epilepsy, especially with drop attacks. Although the posterior approach has been described, the semisitting position remains underutilized and rarely documented in literature. This technique enhances midline visualization, reduces retraction, and allows safer access to posterior interhemispheric structures. Our series illustrates the technical feasibility of this approach, accompanied by operative descriptions and video documentation.

Methods: We retrospectively reviewed 10 patients who underwent posterior two-thirds corpus callosotomy via a right occipital craniotomy in the semisitting position. The surgical corridor enabled direct access to the splenium, Galenic venous system, and pericallosal arteries with only transient use of a fixed retractor. The retractor can be subsequently removed after splenial exposure with sufficient brain relaxation. The clinical and operative outcomes seizure frequency, antiseizure medication changes, hospital disposition, and complications were collected.

Results: Ten patients (mean age = 27 years, epilepsy duration = 22.6 years) underwent the procedure without complications. The median follow-up was 18 (interquartile range [IQR] = 12-28) months. Seven patients experienced drop attacks, and median monthly drop attacks decreased from 36 (IQR = 2.5-70) to 0 (IQR = 0-23) postoperatively. Of those who experienced drop attacks, five of seven achieved complete resolution, and the remaining two achieved a reduction of 66% and 68%. Additionally, nine of 10 patients experienced other seizures besides drop attacks, and these seizures were reduced from 84 (IQR = 72-112) to five (IQR = 1-16) per month. Two patients developed transient disconnection syndrome that resolved spontaneously. No cases of hemodynamic instability or venous air embolism occurred.

Significance: The semisitting posterior callosotomy technique appears to offer favorable anatomical access and gentle tissue handling, with no intraoperative complications in this limited series. Although these preliminary findings are encouraging, further studies should determine its broader applicability and long-term outcomes. This approach may warrant consideration as a surgical option in selected patients with drop attack-dominant epilepsies.