Epilepsia最新文献

Objective: People experiencing homelessness (PEH) are more likely to be diagnosed with epilepsy and to experience seizure-related morbidity and mortality. However, despite the increased prevalence of this condition, there is limited research examining the granular impact of epilepsy on PEH's daily lives and a dearth of research considering the perspectives of PEH themselves. This mixed-methods study aims to address these oversights by comparing the impact of epilepsy on homeless and housed people with epilepsy (PWE). As "impact" can be variously defined and understood, several validated questionnaires measuring psychiatric symptomatology, perceived stigma, epilepsy knowledge, and epilepsy-related quality of life (QoL), respectively, were used as proxies. PEH were also asked open-ended questions about their epilepsy-related experiences, to gather in-depth insights into the ways that epilepsy had shaped their lives.

Methods: This was a mixed-methods study using a study-specific set of questionnaires including the following: sociodemographic information; measures of psychiatric symptomatology, epilepsy-related knowledge, QoL, and stigma; and open-ended questions on the impact of epilepsy on QoL.

Results: PEH and housed PWE were recruited when attending an inner-city Dublin hospital. Data from 62 participants were included, 13 PEH and 49 housed participants. The results demonstrated that PEH had a higher burden of psychiatric symptomatology than housed PWE, including higher anxiety (p = .001) and depression (p < .001) scores. Once this was adjusted for, there was no difference in QoL between the two groups. PEH also reported significantly more epilepsy-related stigma relative to housed PWE (total revised Epilepsy Stigma Scale mean = 5.7 ± 3.0 vs. 1.6 ± 2.5, p < .001). PEH emphasized the emotional and affective burden that epilepsy presented in their lives.

Significance: This research emphasizes the need for clinicians to remain cognizant of the social context in which chronic disease emerges and the importance of targeted, holistic, and multidisciplinary models of care to improve QoL and alleviate stigma for PEH experiencing epilepsy.

Objective: Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) plays a crucial role in dendritic spine morphogenesis and excitatory synapse formation. We establish de novo variants in BAIAP2 as a novel genetic cause for developmental and epileptic encephalopathies (DEEs).

Methods: Using whole exome/genome sequencing, we identified de novo missense variants in BAIAP2 in six patients with DEEs. Molecular docking was utilized to predict the effect of these variants on the protein structures. Functional assays were conducted by overexpressing wild-type and mutant BAIAP2 in cultured cells, primary hippocampal neurons, and zebrafish.

Results: All six patients exhibited severe infantile or early childhood onset epilepsy, with refractory seizures in four individuals. Language and motor development delays were prevalent, with varying degrees of intellectual disability observed. The missense variants were clustered within the multiple phosphorylation site region that is critical for the autoinhibited conformation of BAIAP2 through 14-3-3 binding. In silico modeling and HeLa cell spreading assays demonstrated that BAIAP2 mutants potentially disrupted its autoinhibited state and induced hybrid filopodia-lamellipodia protrusions in cells, phenocopying the effects of Rac1/Cdc42 overexpression. Electrophysiological recordings revealed that neurons expressing BAIAP2 variants exhibited increased excitability, due to enhanced excitatory synaptogenesis. Additionally, transgenic overexpression of mutant BAIAP2 mRNA in zebrafish embryos led to developmental defects, abnormal neurite growth, and enhanced sensitivity to pentylenetetrazole-induced locomotor hyperactivity.

Significance: De novo variants in BAIAP2 represent a novel cause of DEEs. The functional consequences of these variants suggest that the gain of function of BAIAP2 can affect filopodia-lamellipodia formation, dendritic spine development, and synaptic transmission.

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.

This study was undertaken to systematically evaluate the efficacy of cell therapy in reducing seizures in animal models of chronic epilepsy. Three databases, Ovid MEDLINE, Ovid Embase, and Web of Science, were searched using predetermined eligibility criteria. The relevant preclinical controlled studies were included for review and meta-analysis using a random-effects model to calculate summary estimates of the effect size (percentage reduction in seizures). The degree of heterogeneity among the included studies was assessed using the I² statistic. Subgroup meta-analysis and meta-regression were performed to further elucidate the sources of heterogeneity. Thirty published studies met the eligibility criteria, including a total of 1306 animals. The majority of studies used kainic acid and pilocarpine status epilepticus models of mesial temporal lobe epilepsy (MTLE). The random effects model revealed an overall reduction in seizure frequency of 54.8% (95% confidence interval = 48.0558-61.5455) compared to the control, and the heterogeneity was 87.1% among the included studies. The meta-regression revealed that seven study characteristics significantly accounted for the between-study heterogeneity. They can be grouped into three broad categories: epilepsy-specific, animal-specific, and cell transplantation-specific. The greatest seizure reduction was observed in the post-kainic acid status epilepticus model of chronic MTLE, when the cells were delivered intravenously and when the seizure reduction was measured as seizure frequency. Embryonic stem cell transplantation showed the greatest efficacy in reducing seizures. Cell transplantation shows favorable efficacy as a treatment that can reduce seizure recurrence in chronic animal models of epilepsy. High heterogeneity between studies reflects the diverse methodologies employed in preclinical research on cell therapy for epilepsy. Despite these encouraging findings, the high risk of publication bias and variability in study design emphasize the need for further robust preclinical studies to confirm these reported outcomes.

Objective: The effectiveness of surgery in drug-resistant epilepsies is often focused exclusively on seizure control. The Epilepsy Surgery Satisfaction Questionnaire-19 (ESSQ_19), developed in 2020, is a reliable tool for assessing the level of satisfaction of patients undergoing surgery. We aimed to perform a Spanish translation, adaptation, and validation of the ESSQ_19 questionnaire.

Methods: This was a prospective multicenter study (five Spanish-speaking countries) including an international cohort of adult patients who underwent epilepsy surgery at least 1 year prior to participation. We followed a translation and back-translation methodology to obtain the Spanish version of the questionnaire (ESP-ESSQ_19). For validation, internal consistency (Cronbach alpha) and test-retest reliability at 6 months were assessed, and psychometric properties were measured by correlating them with parallel aspects using validated questionnaires.

Results: One hundred fifty patients were included (59.3% women; mean age = 39.3 ± 13 years, interquartile range [IQR] = 28-49 years), of whom 94 completed the baseline and follow-up questionnaires, with a median time since surgery of 3 (IQR = 1-7) years. Temporal lobe epilepsy was the most common (n = 112, 77.8%), as was structural etiology (n = 139, 95.2%). At inclusion, 101 patients (68.7%) had been seizure-free for ≥1 year. The ESP-ESSQ_19 questionnaire showed an internal consistency index of .88-.95 for all domains and a test-retest reliability of .91 (95% confidence interval = .87-.94). Significant correlation coefficients were observed between the ESP-ESSQ_19 questionnaire and all validated questionnaires used.

Significance: The ESP-ESSQ_19 questionnaire is a Spanish-language instrument useful for assessing patient satisfaction after epilepsy surgery, with adequate psychometric properties that allow its use in clinical practice and in research.

Objective: Genetic testing can be necessary in the early diagnosis or confirmation of Dravet syndrome (DS). Despite major advances in availability of genetic testing, several barriers to timely testing persist. These include clinician recognition of the disease in its early stages and health disparities. Early diagnosis of DS has a growing list of management implications, including antiseizure medication selection, appropriate counseling regarding prognosis, access to resources, and clinical trial access.

Methods: To understand the barriers to early genetic testing in DS, we performed a retrospective chart review of patients with DS due to SCN1A variants and analyzed factors hypothesized to affect time to testing. Factors including the initial clinical presentation and health disparities were correlated with length of time to testing from the first documented seizure.

Results: Factors significantly correlated with time to testing included absence of early status epilepticus and the need for an English-language interpreter. Interestingly, neither race/ethnicity nor a composite social deprivation index were significantly correlated with delays in genetic testing in our population.

Significance: We identified significant factors associated with delay to genetic testing in DS. Purposefully addressing these factors through education and resources will likely be important for continued improvement in early and equitable diagnosis for patients with DS.

Objective: Interictal epileptiform discharges (IEDs) in people with epilepsy (PWE) can impair cognitive functions and increase reaction time (RT) and the likelihood of missed reactions. These effects are not routinely assessed, because reliable methods for detecting IEDs of variable appearance in real time and suitable tests to measure IED effects do not yet exist. The objective was to assess different IED effects using new artificial intelligence and medical electronics.

Methods: The Digital Response Test in Epilepsy (DigRTEpi) consisted of a laptop and electronic circuits in a closed loop. Our model with Markov Transition Fields and a deep neural network (ResNet34) visualized the electroencephalogram (EEG) and classified the resulting images. IED detection triggered stimuli in a driving game or in a new cognitive assessment, the interictal Automated Responsiveness Test (iART). DigRTEpi was validated in a prospective case series with 20 people with focal and generalized epilepsies. During offline analysis, sensitivity, specificity, false-positive IED detection rate, latency of EEG classification, IED-induced RT prolongation, virtual crashes, and impaired responses to neuropsychological tasks were determined.

Results: The model detected IEDs with 84% sensitivity and 96% specificity in our training dataset. In the prospective study with 20 PWE, median sensitivity was 90% (95% confidence interval [CI] = .81-.95), and false-positive IED detection rate was 2.8 (95% CI 2.1-5.9). The ongoing EEG was classified window-by-window in a median 98.7 ms (95% CI = 98.0-99.4). Median RT prolongation and crash probability due to IEDs were 43.8 ms (95% CI = 20.3-64.7) and .9% (95% CI = 0-6.0) per person, respectively. Two patients (10%) had delays of >100 ms, found to be clinically relevant in our prior publication. IEDs caused four patients (20%) each to respond incorrectly or miss answers to neuropsychological tasks. The median false-positive IED detection rates were 2.8/min (95% CI = 2.1-5.9; driving game) and 2.1/min (95% CI = 1.5-3.2; iART).

Significance: By effectively detecting IEDs of variable morphology in real time, DigRTEpi assessed the severity of IED-associated transitory impairment of virtual driving and cognition to improve personalized care.

Objective: Conditions presenting with both epilepsy and movement disorders (EPIMDs) range from relatively benign cases to severe developmental encephalopathies. However, the full clinical and genetic spectrum still needs to be better defined. The aim of this study is to describe the presentation of EPIMDs in pediatric patients with known genetic etiologies, correlating these features with age at onset and underlying pathological mechanisms to identify patterns that could improve patient management.

Methods: We retrospectively analyzed the clinical records of pediatric patients who underwent genetic testing for EPIMDs at our institution between 2009 and 2022. Genetic testing included single-gene Sanger sequencing, multigene next-generation sequencing panels targeting epilepsy and/or MDs, and array comparative genome hybridization. Demographic, clinical, and electroencephalography (EEG) data were collected. Statistical analyses were conducted using multivariate and cluster analyses.

Results: A total of 97 subjects were included. The mean age ± SD at epilepsy onset was 3.6 ± 4.4 years, whereas the mean age at MD onset was 5.2 ± 4.9 years. Based on the mechanism of genetic dysfunction, we identified six groups: transportopathies (n = 18), synaptopathies (n = 11), channelopathies (n = 18), metabolic disorders (n = 15), intracellular trafficking defects (n = 8), and unknown/complex function disorders (n = 27). Cluster analysis identified three distinct groups: (1) early-onset epilepsy and paroxysmal MDs with normal intelligence quotient (IQ) and mild intellectual disability, associated with transportopathies (n = 38); (2) early-onset epilepsy with dystonia and myoclonus, low IQ, and developmental and epileptic encephalopathy, associated with channelopathies (n = 31); (3) epilepsy onset between 1 and 5 years of age with developmental delay, parkinsonism, and low IQ, associated with metabolic etiology (n = 26).

Significance: Our study demonstrates that, despite the phenotypic and genetic pleiotropy observed in EPIMDs, a precise characterization of semiological and cognitive features remains essential to support variant interpretation and to refine the diagnostic process and patient management in these rare conditions.

Objective: To characterize the clinical, electroencephalographic, and genetic features of epilepsies featuring absence seizures within monogenic etiology, highlighting the diagnostic, treatment and prognostic implications.

Methods: We conducted a retrospective, multicenter study including patients with monogenic epilepsies and electroencephalography (EEG)-documented absence seizures. We analyzed clinical data, electroclinical findings, neurodevelopmental outcomes, and treatment responses through standardized questionnaires and medical records. We classified genetic variants according to American College of Medical Genetics and Genomics (ACMG) guidelines and performed univariate and multivariate analyses to identify predictors of developmental outcomes.

Results: We included 160 patients (111 female; median age at last follow-up: 13 years) with absence seizures and confirmed pathogenic or likely pathogenic monogenic variants. The most frequently implicated genes were SLC2A1, SLC6A1, SYNGAP1, CHD2, and SCN1A. Four genes-HESX1, NCKAP1, SON, STARD9-had not been previously associated with absence seizures. In 35% of patients, absence seizures were the only seizure type and in 67% were the initial manifestation. Atypical features included irregular EEG discharges (56%) eyelid myoclonia (42%), and automatisms (33%). Early-onset (before age 3) seizures occurred in 58% and was significantly associated with atypical features (p < .03). Using existing International League Against Epilepsy (ILAE) epilepsy syndrome classification, 60% of patients could not be classified. Developmental delay occurred in 54%, intellectual disability in 65%, and other neurodevelopmental comorbidities in 49%. Predictors of poor developmental outcomes included early developmental delay, drug-resistant epilepsy, and early absence onset. We found no difference in the prevalence of drug resistance across the various genetic etiologies. The most effective medications for absence seizures included valproate, ethosuximide, benzodiazepines, and lamotrigine. Disease-specific therapies (e.g., ketogenic diet in SLC2A1, stiripentol/fenfluramine in SCN1A) were effective in select cases.

Significance: Absence seizures are a common manifestation of different monogenic epilepsies, often associated with early onset, atypical clinical and/or EEG features, developmental delay or drug resistance. Classification models should incorporate genetic data alongside electroclinical features, especially as next-generation sequencing is increasingly used.

Objective: This study was undertaken to study long-term memory trajectories over the years in patients with temporal lobe epilepsy and unilateral hippocampal sclerosis (TLE/HS) seizure-free since surgery.

Methods: This cross-sectional study included patients with TLE/HS from a single-center epilepsy surgery program who had been seizure-free for at least 10 years following anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Memory performance was evaluated preoperatively (T1), 1-4 years postoperatively (T2), and 10-15 years after surgery (T3). Logistic regression evaluated variables correlated with memory function at each point in time. A reliable change index was performed to identify changes in individual measures.

Results: A total of 54 patients were included, of whom 36 (66%) were male and 52 (96%) right-handed. Patients with left HS and normal preoperative Rey Auditory Verbal Learning Test or Wechsler Memory Scale-Revised (WMS-R) logical memory showed worsening at T2 (13% × 52%, p = .029; 0 × 31%, p < .015, respectively) and T3 (27% × 63%, p = .045; 22% × 81%, p < .001, respectively). Visual reproduction (WMS-R) following nondominant surgery also deteriorated at T3 for patients who improved or sustained normal performance between T1 and T2 (33% × 50%, p = .64). The predictive factors for memory decline included normal preoperative memory function (odds ratio [OR] = 15, 95% confidence interval [CI] = 4.03-55.9, p < .001 for logical memory; OR = 1.5, 95% CI = 1.12-2.01, p = .007 for visual reproduction), younger age (OR = 1.2, 95% CI = 1.12-1.28, p < .001), dominant-side surgery (OR = 3.66, 95% CI = 1.49-8.95, p < .01), and lower education level (OR = 8.74, 95% CI 1.77-43.2, p = .008). The SAH technique was associated with better long-term verbal learning outcomes compared to ATL (OR = 3.02, 95% CI = 1.17-7.81, p = .02).

Significance: Memory preservation or improvement in the first few postoperative years is usually not sustained in the long term, suggesting that disease progression surpasses plasticity over the years.