Epilepsia最新文献

Objective: In children with tuberous sclerosis complex (TSC) and drug-resistant epilepsy (DRE), magnetic resonance imaging-guided stereotactic laser ablation (SLA) therapy offers less-invasive treatment compared to craniotomy and resection. Our study seeks to further expand on the long-term outcomes in patients with TSC-related DRE who have undergone SLA.

Methods: Patients with TSC and DRE treated with SLA, between July 1, 2016 and January 1, 2022, at our institution were identified retrospectively. Reduction in number of anti-seizure medications (ASMs), developmental improvement as reported by the patients' families, seizure frequency measured in surgically targeted seizure type and total seizures per day, and Engel classification were evaluated at 6 months, 1 year, 2 years, and thereafter at the most recent follow-up visit if available.

Results: Forty patients (ages 11 months to 23 years, median age 3.6 years) with TSC underwent SLA. Total follow-up was on average 2.9 years post-surgery. Significant (>50%) reduction in total seizure frequency occurred in 80% of patients (n = 32), with 63% of patients reporting a >90% reduction in seizure frequency (n = 25) at last follow-up. Fifty-eight percent had complete freedom from their surgically targeted seizure type (n = 23). At last follow up, perceived developmental gains occurred in 63% (n = 25), reduction in ASM occurred in 40% (n = 16), and Engel class was III or less in 93% of patients (n = 37).

Significance: SLA was safe and effective for most patients, even the very young. A majority of patients achieved improvement in seizure frequency, including the surgically targeted seizure type, but less than half were able to reduce medications. Reported developmental improvement was related to Engel outcomes. Future studies utilizing neuropsychological testing in the full cohort will be required to offer objective insights into post-operative development profiles.

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.

This prospective multicenter study aimed to evaluate the applicability and feasibility of the updated International League Against Epilepsy (ILAE) seizure classification (basic version) in secondary referral centers, using information from history-taking and basic investigations (routine or sleep electroencephalography, and computed tomography or magnetic resonance imaging when indicated). The primary outcome was the proportion of patients whose seizures could be classified. Secondary outcomes addressed the new elements introduced in the updated classification: ictal responsiveness and recall (awareness) for classifying the state of consciousness, and the basic seizure descriptors (with vs. without observable manifestations). Data from 458 consecutive patients (152 pediatric) across seven outpatient epilepsy clinics were analyzed. All seizures could be classified according to the basic version of the updated ILAE seizure classification. Information on awareness was available in 396 patients (86.5%) and on responsiveness in 380 (83.0%). In 11 patients (2.4%), the ictal state of consciousness could not be determined. Information on basic seizure descriptors was available for 452 patients (98.7%). These findings indicate that the basic version of the updated ILAE seizure classification is feasible and applicable at secondary referral centers. Moreover, state of consciousness and basic seizure descriptors can be inferred from history in nearly all patients.

Objective: Variants in GABRG2, encoding the γ2 subunit of the γ-aminobutyric acid type A receptor, are linked to epilepsy phenotypes of varying severity, with gain-of-function (GoF) variants associated with the more severe phenotypes than loss-of-function variants. Here, we provide a comprehensive analysis of the early clinical features, motor, language, and eating abilities, and structural consequences of the recurrent GABRG2 p.(Ala106Thr) GoF variant, aiming to refine genotype-phenotype correlations and deepen the understanding of GoF-associated GABRG2 disorders.

Methods: Individuals were recruited through international collaborations, literature review, and patient advocacy groups. Clinical data were collected via standardized interviews and physician reports. Functional effects were assessed using electrophysiological recordings. Structural modeling was performed using homology-based approaches to evaluate conformational changes.

Results: We collected 23 unrelated individuals harboring the GABRG2 p.(Ala106Thr) variant. Symptoms began with early dysphagia (median onset age = 1 month), hypotonia, seizures (median onset age = 2 months), and hyperkinetic movement disorders (median onset age = 3 months). Epilepsy was present in 91% of the individuals, 71% featuring a developmental and epileptic encephalopathy; 33% of the individuals with epilepsy achieved seizure freedom during the follow-up. All individuals exhibited moderate to severe cognitive/neurodevelopmental impairment, with profound deficits in motor, language, and other domains. Functional analysis confirmed a GoF effect of the p.(Ala106Thr) variant. By contrast, another variant affecting the same residue, p.(Ala106Pro), which is observed in population databases, was functionally characterized as neutral. Structural modeling indicated that the p.(Ala106Thr) variant may enhance receptor gating by facilitating a hydrogen bond between the extracellular and transmembrane domains, a mechanism not observed with the p.(Ala106Pro) variant.

Significance: Although some individuals exhibited severe developmental impairment without epilepsy, our findings demonstrate that the recurrent GABRG2 p.(Ala106Thr) GoF variant is consistently associated with a severe neurodevelopmental phenotype. Despite its profound clinical impact, in silico tools consistently predict this variant as benign, highlighting a critical gap in current predictive models.

Objective: Stereoelectroencephalography (sEEG) is commonly employed in the workup for epilepsy surgery in patients with focal drug-resistant epilepsy (DRE). Intracranial hemorrhage is a known complication, with reported incidence rates ranging from .9% to 19.1%. Rarely, pseudoaneurysms have been reported in literature as a potential cause. This retrospective cohort study aims to describe the occurrence, clinical characteristics, and management of iatrogenic pseudoaneurysms following sEEG and the clinical outcome of the described cases.

Methods: A cohort of 395 patients (4067 depth electrodes) with DRE who underwent sEEG was retrospectively analyzed. The identified patients with pseudoaneurysms were analyzed in detail, focusing on timing of detection and location of the aneurysms, clinical characteristics, management strategies, and clinical outcome.

Results: A symptomatic iatrogenic pseudoaneurysm was identified in six of 395 cases (1.5%), with a per-electrode risk of .15% (6/4067); all occurred at the M2/M3 branches of the middle cerebral artery. All six cases presented with intracerebral or subarachnoid hemorrhage. Aneurysms were detected with combined cerebral computed tomographic angiography (CTA) and digital subtraction angiography (DSA) and treated without complications by surgical clipping or endovascular embolization. The depth electrode implantation and planned sEEG recording had to be either prematurely discontinued or canceled in four of six cases. No patients died; five experienced neurological symptoms and required prolonged hospitalization, with four needing additional rehabilitation.

Significance: Pseudoaneurysms following sEEG represent a serious complication with significant clinical consequences and warrant early detection and intervention. Occurrence is underreported in literature. It is recommended to use CTA and DSA when a pseudoaneurysm is suspected, particularly in cases of intraparenchymal or subarachnoid hemorrhage, and especially when depth electrodes are in close proximity to a blood vessel.

Thalamic deep brain stimulation (DBS) represents an emerging therapeutic option for patients with focal drug-resistant epilepsy who are ineligible for or have failed resective surgery. To optimize outcomes and guide DBS lead placement, thalamic stereoelectroencephalography (SEEG) has been proposed. This monocentric retrospective study aimed to identify interictal and ictal SEEG biomarkers of the medial pulvinar (PuM) associated with favorable PuM-DBS response. Six patients (four female, two male) underwent SEEG including PuM sampling, were deemed unsuitable for resective surgery, and subsequently received bilateral PuM-DBS. In total, eight PuMs were sampled in SEEG: four bilaterally (two patients) and four unilaterally (four patients). The SEEG exploration covered both the PuM and the ipsilateral epileptogenic zone network (EZN) in four patients, whereas in the other two the EZN was bilateral but PuM sampling was unilateral. All SEEG signal analyses were performed on the PuM sampling contacts available in each patient. Interictal SEEG analysis included spike rates and nonlinear functional connectivity (h2), whereas ictal analyses combined visual inspection with quantitative biomarkers: epileptogenicity index (EI), connectivity epileptogenicity index (cEI), permutation entropy index (PEI), and delta entropy (ΔE). Two patients were responders (≥50% seizure reduction at 1 year). PuM spike rates, connectivity, and EI and cEI values did not differentiate responders from nonresponders. In contrast, entropy-based measures were significantly higher in responders: PEI (false discovery rate [FDR]-p = .024) and ΔE (FDR-p = .034). These findings suggest that ictal PuM complexity disruption, quantified through entropy-based SEEG metrics (PEI and ΔE), may represent a candidate biomarker of response to medial pulvinar DBS and warrants validation in larger cohorts.

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epilepsy often accompanied by executive dysfunction, affective symptoms, unfavorable behavior, and social outcomes, yet its impact on theory of mind (ToM) remains underexplored. We conducted an unmatched case-control study assessing 34 JME patients and 48 healthy controls, adjusted for age, sex, education, intelligence quotient, anxiety, and depression. Participants completed a brief version of the Faux Pas Recognition Test (FPRT) and the Reading the Mind in the Eyes Test, alongside measures of executive function, prospective memory, and mood. In raw analyses, JME patients showed significantly lower FPRT total scores (mean ± SD = 22.9 ± 9 vs. 27.5 ± 7, p = .01) and FPRT Understanding (.80 ± .11 vs. .87 ± .14, p = .02). After adjusting for cognitive and affective covariates via propensity scoring, group differences in ToM performance were no longer significant (p > .20). These results suggest that ToM deficits in JME are mediated by broader cognitive and affective disturbances rather than reflecting a social cognitive impairment. Future longitudinal studies with larger samples and tighter pharmacological control are warranted.

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.

Objectives: Although depression is one of the most common psychiatric comorbidities among individuals with epilepsy, data specific to older adults with epilepsy are scarce. We examined the trajectory of depressive symptom scores in older adults with and without epilepsy.

Methods: The Cardiovascular Health Study is a population-based longitudinal cohort of U.S. adults 65 years of age or older. Depression scores were measured annually using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) for up to 9 years of follow-up. We used a linear mixed model to estimate mean CESD-10 scores and percent with depression (CESD-10 score ≥10) over time by epilepsy status, adjusted for demographics, health behaviors, clinical characteristics, and measures of life satisfaction.

Results: CESD-10 scores increased at a significantly faster rate over 9 years among older adults with epilepsy (n = 190; 2.8 points) compared to those without epilepsy (n = 5264; 1.8 points; p = 0.005), adjusted for the covariates specified above. The proportion of those who met the threshold for depression also increased at a significantly faster rate among older adults with epilepsy compared to those without epilepsy. The proportion with depression increased by 19.8 cases per 100 (95% confidence interval [CI]: 12.9-26.6) in older adults with epilepsy, compared to an increase of 10.2 cases per 100 (95% CI: 9.0-11.4) in those without epilepsy (a difference in the increase of 9.6 additional cases per 100 [95% CI: 2.7-16.5]; p = 0.007), adjusted for covariates. The association of epilepsy with CESD-10 score trajectory did not differ by sex.

Significance: Older adults with epilepsy experience worse depressive symptom trajectories over time compared to older adults without epilepsy, with one in five individuals experiencing depression over 9 years. These findings highlight the need for systematic and repeated screening of depression in older adults with epilepsy.