Epilepsia最新文献

Objective: N-of-1 trials aim to determine the therapeutic effect for a single individual. This individualized approach necessitates collecting multiple data points over time through repeated alternating periods of active treatment and a comparator or control condition. The extended duration of the treatment periods may increase patient burden, prolong placebo exposure, and increase the likelihood of study discontinuation. In theory, treatment responders (or non-responders) can be identified early during the trial if the therapeutic effect is strong (or completely lacking). There are no theoretical constraints to evaluate treatment efficacy more regularly-instead of only after a predetermined number of treatment periods. Regularly updating estimates on treatment effects allows clinicians to accelerate clinical decision-making regarding N-of-1 study termination. This study examined the value of continuous treatment effect estimation using Bayesian hypothesis testing in N-of-1 trials to accelerate and nuance clinical decision-making.

Methods: An N-of-1 trial with severe epilepsy was simulated and three N-of-1 trials in neurological conditions were (re-)analyzed continuously with consecutive data points using Bayesian hypothesis testing and/or a minimally clinically important threshold (30% seizure frequency reduction). Trial duration based on Bayesian testing with strong evidence for treatment effects was compared to original trial duration.

Results: Original trial duration could be reduced between 9.5% and 35% of the trial length by using continuous outcome estimation in two of the analyzed trial examples. The moment that strong evidence supporting beneficial treatment effects using Bayesian hypothesis testing and a significant probability of minimally clinically important differences are achieved during the trial may differ. Obtaining additional data points and alternating interventions over time improve certainty of the estimates of treatment effects.

Significance: Treatment efficacy decisions can be expedited when outcome estimation is performed continuously rather than delayed until the end of the trial. Clinical significance of N-of-1 trial outcome can be improved combining both Bayesian hypothesis testing and a minimally clinically important threshold.

Objective: This study aimed to investigate the long-term risk of posttraumatic epilepsy (PTE) and psychogenic nonepileptic seizures (PNES) following mild traumatic brain injury (mTBI) in combat veterans and to evaluate the predictive value of early electroencephalographic (EEG) abnormalities and the impact of trauma mechanism (blast vs. nonblast).

Methods: A retrospective observational study was conducted in 2000 war veterans followed for 5 years after the Second Karabakh War (2020-2025). Veterans with mTBI (n = 1000), defined by International Classification of Diseases, 10th Revision (ICD-10) code S06.0 and standard clinical criteria (loss of consciousness for ≤30 min, confusion for <24 h, normal computed tomography/magnetic resonance imaging), and controls without TBI (n = 1000) were compared for the incidence of PTE and PNES. Within the mTBI group, cases were stratified by trauma mechanism (blast-related vs. non-blast-related). Early EEGs (≤7 days) were analyzed for abnormalities predictive of PTE. PTE was defined as unprovoked seizures occurring >7 days after injury (ICD-10G40.x) and PNES as F44.5. Statistical analyses included chi-squared tests, Kaplan-Meier analysis, and Cox proportional hazards models.

Results: During the 5-year follow-up, epilepsy developed in 4.5% of the mTBI group compared with 1.3% of controls (p < .001). Blast-related injuries had a higher 5-year PTE incidence than nonblast trauma (5.7% vs. 2.3%, p = .019). More than half of PTE cases occurred within the first postinjury year. Early EEG abnormalities were observed in 20% of the mTBI group, and epileptiform discharges were strongly associated with subsequent PTE. PNES occurred in 7.1% of mTBI and 2.4% of controls (p < .001); 65% of PNES cases in the mTBI group were comorbid with PTSD.

Significance: Even mild TBI can induce long-term epileptogenesis, particularly after blast exposure. Early EEG abnormalities, especially epileptiform discharges, serve as strong predictors of PTE. These findings emphasize the need for early electrophysiological screening and long-term neuropsychiatric follow-up in veterans with mild head injury.

Objective: Conceptualizing functional/dissociative seizures (FDS) as resulting from dissociation, or conversion, we hypothesized that, compared to epileptic seizures (ES), FDS should carry more symbolic or communicative content and that this would allow observers to distinguish FDS from ES.

Methods: Three independent, epileptologically naive raters evaluated home videos of patients with confirmed diagnoses of either FDS or ES using a standardized form. The focus of the ratings was explicitly not on seizure semiology, but on verbal and nonverbal behavior, the role of proxies, interaction patterns, communication, emotional tone, symbolic content, and situational context.

Results: Of 598 home videos available from 183 patients, 215 ES and 95 FDS videos were suitable for analysis. No explicit symbolic communication was identified. FDS showed more passive, withdrawn behavior, and the postictal phase-captured more often than the ictal period-was particularly helpful for distinguishing FDS from ES. Interrater reliability was moderate. Features observed more commonly in FDS included closed eyes, recumbent posture, repetitive movements, reduced eye contact, responses to caring behavior, and occurrence in private settings. Raters perceived greater emotional distress in FDS and reported more distress watching these videos. Logistic regression based on all ratings correctly classified 94% of ES but only 32% of FDS.

Significance: Home video analysis captures important contextual and behavioral features of FDS and ES. The differential diagnostic reliability of lay raters' perceptions is limited. Findings suggest that FDS comprise passive rather than active appellative communication, likely reflecting emotional regulation processes. In contrast, in the home videos studied, ES patients exhibit greater postictal awareness and interaction than FDS patients, pointing to the relevance of the postictal phase for discriminating both seizure types. The results emphasize integrating environmental context and patient-caregiver interactions before, during, and after seizures to understand the functional significance of FDS in naturalistic, nonclinical settings.

Objective: SCN2A loss-of-function (LoF) variants are associated with epilepsy (onset age ≥ 3 months), intellectual disability (ID), and autism spectrum disorder (ASD). Despite numerous identified variants and the description of phenotypic subgroups, relationships between Na_v1.2 channel dysfunction and clinical phenotypes remain unclear. This study examined how distinct LoF mechanisms relate to phenotypic outcomes.

Methods: Whole-cell patch-clamp electrophysiology was used to characterize 15 presumed LoF SCN2A variants. Mechanism-phenotype correlations were assessed in 33 patients with these variants (six recurrent) and 41 patients with 15 previously characterized LoF variants (four recurrent). Phenotypic subgroups were categorized as later onset epilepsy-midinfancy (onset between 3 and 18 months), later onset epilepsy-childhood (onset after 18 months), ID/ASD without epilepsy, and "other" for unclassified cases.

Results: Of the 15 electrophysiologically characterized SCN2A variants, 11 caused total Na_v1.2 LoF, three caused partial LoF, and one showed mixed LoF and gain-of-function (GoF) effects. Among previously published variants, seven showed total LoF, five partial LoF, and two mixed LoF/GoF, and one was undetermined. Across both cohorts, seven of 10 recurrent variants (70%) were associated with multiple phenotypic subgroups. Partial or total Na_v1.2 LoF variants were identified in all subgroups. Notably, a midinfancy epilepsy phenotype was observed in 22 of 24 individuals (92%) carrying a mixed LoF variant, with phenotype data unavailable for seven additional individuals. A novel LoF-associated phenotype-episodic ataxia with or without developmental delay or ID-was identified in five of six individuals with the L1650P variant. Although episodic ataxia has been previously associated with GoF variants in SCN2A, this is the first reported instance in individuals with a confirmed LoF variant.

Significance: Distinct SCN2A LoF phenotypes cannot be reliably linked to specific biophysical mechanisms, as both total and partial Na_v1.2 LoF occurs across diverse phenotypes. For efficient personalized treatment, it is crucial not to rely solely on clinical phenotype to predict the underlying LoF mechanism.

Objective: To determine the prevalence and possible causes of amygdala enlargement in patients with drug-resistant temporal lobe epilepsy.

Methods: Patients were retrospectively identified via a radiology information system and a large language model. Magnetic resonance imaging scans were visually re-analyzed and amygdala volumetry applied.

Results: The term "amygdala" was used in 89 of 1853 patients. Of those, 54 had lesions in the amygdalae, 20 had isolated amygdala enlargements, and 15 patients had amygdala enlargements and remote epileptogenic lesions. Objective processing of imaging data confirmed higher amygdala volumes of both latter groups (2.09 ± 0.28 mL, 2.23 ± 0.33 mL vs 1.56 ± 0.22 mL).

Significance: When amygdala enlargement occurs with remote epileptogenic lesions and patients become seizure-free after remote lesion resection, amygdala enlargement is likely the consequence of seizures, but not their cause. In addition, isolated amygdala enlargements can be the consequence of epileptic seizures.

Objective: Long-term memory deficits are often seen in patients with temporal lobe epilepsy (TLE). Recently, studies showed that patients with hippocampal sclerosis (HS) type 2, which presents with severe neuron loss in CA1 only, performed within the normal range. However, up to 30% of HS type 2 cases have memory deficits. As insulin-like growth factor 1 (IGF-1) is related to neurogenesis and memory performance, we sought to investigate a possible link between the expression of IGF-1 receptor (IGF-1R) and verbal memory performance among patients with HS type 2.

Methods: We selected 21 patients with left-side TLE and HS type 2. Based on presurgical neuropsychological assessment, we divided the patients into a group with normal long-term verbal memory (Preserved group, n = 15) and another with memory deficit (Deficit group, n = 6). To classify the patients, we used performance on the late recall subitems in the Logical Memory test of the Wechsler Memory Scale and late recall in Rey Auditory Verbal Learning Test (RAVLT). Coronal hippocampal sections at the body level were submitted to immunohistochemistry for NeuN and IGF-1R to evaluate neuron density and IGF-1R expression, respectively.

Results: Patients with preserved memory had the same clinical characteristics as those with memory deficit. The groups had no difference on the short-term subitem of Logical Memory or on RAVLT learning. The Deficit group had lower scores on both long-term memory subitems. Neuron density was also similar among patients in the Preserved and Deficit groups. IGF-1R expression was significantly higher in the granule cell layer and in CA2 in the Preserved group compared to the Deficit group, and IGF-1 expression had strong positive correlation with both the learning and long-term subitems of RAVLT.

Significance: Lower IGF-1 pathway activity is associated with long-term memory deficit in patients with HS type 2.

Objective: This study was undertaken to evaluate whether synaptic vesicle protein 2A (SV2A) expression on peripheral immune cells predicts treatment response to levetiracetam in epilepsy.

Methods: High-dimensional flow cytometry was used to prospectively assess SV2A expression on immune cells from levetiracetam responders, nonresponders, and healthy controls. SV2A expression levels were further validated using real-time quantitative polymerase chain reaction (RT-qPCR) in an independent retrospective cohort. The predictive value of SV2A expression on naive CD8⁺ T cell-specific SV2A/CD3⁺ median fluorescence intensity (MFI) ratio was determined, and correlations with central nervous system (CNS)-resident cell expression were examined in the wild-type (WT) C57BL6 mouse model.

Results: Naive CD8⁺ T cells showed significantly lower SV2A expression (p = .0029) in nonresponders compared to responders, confirmed by RT-qPCR (p = .0022), with no difference in overall CD8⁺ T-cell abundance. The naive CD8⁺ T cell-specific SV2A/CD3⁺ MFI ratio (>.4733) correctly identified most responders, with a positive predictive value of 81.8%. SV2A concentration was stable over time (mean interval = 121.2 days, 95% confidence interval = 93.64-148.7 days), unaffected by age, gender, dose, or treatment duration, and neuronal SV2A expression in the CNS of WT C57BL6 mice correlated with SV2A expression of CD8⁺ in circulating blood cells (r = .655, p = .008).

Significance: Naive CD8+ T cell-specific SV2A MFI ratio may represent a potential indicator of treatment response for levetiracetam. Pending further validation, its stability and accessibility suggest that it could potentially support treatment decisions and help to reduce ineffective drug trials.

Despite advancements in epilepsy care, a substantial diagnostic gap persists, particularly in resource-limited settings. This narrative review explores the potential of video-based diagnostics augmented by artificial intelligence (AI) to address this gap by enabling earlier and more accessible seizure detection and classification. We reviewed literature on the diagnostic utility of video-only seizure recordings, advances in AI-driven video analysis, and existing implementation models. We synthesized clinical, technological, and health-economic perspectives to propose a framework for integrating video-based diagnostics into epilepsy care. Smartphone-recorded videos provide diagnostically relevant semiological data across age groups and seizure types. Manual expert video review establishes a high diagnostic baseline; a meta-analysis of 13 studies (n = 682) demonstrated a pooled sensitivity of 82.2% and specificity of 84.7% for differentiating epileptic events. Advancements in AI and computer vision are effectively automating this process; our review of eight pivotal validation studies indicates that deep learning algorithms now achieve sensitivities of 82%-100% for convulsive seizures in controlled settings. However, performance varies significantly in real-world environments, with false detection rates ranging from .05 to >12 per night depending on the setting and seizure type. Implementation challenges include data scarcity, generalizability, regulatory frameworks, and reimbursement gaps. Widespread adoption requires standardized protocols, validated algorithms, secure data infrastructure, and economic incentives. Overall, video-based diagnostics, particularly when enhanced by AI, represent an underutilized and scalable opportunity to close the epilepsy diagnostic gap. They offer potential to reduce diagnostic delays, improve seizure classification, and increase access to expert care across clinical settings, including homes, emergency departments, and low-resource regions. Strategic investment in research, infrastructure, and policy reform is needed to fully realize this vision.

Objective: Epilepsy surgery is an effective treatment option for patients with medically refractory epilepsy due to mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE). The success of surgery depends on the accurate localization of the epileptogenic zone, which can be challenging due to the subtle imaging features. The aim of this project was to provide an in-depth electro-clinical characterization of MOGHE in patients with medically intractable epilepsy, and to assess the role of stereo-electroencephalography (SEEG) in tailoring the resection and optimizing surgical outcome.

Methods: This single-center retrospective study analyzes a cohort of patients with medically intractable focal epilepsy who underwent surgery and had confirmed MOGHE on pathology evaluation. Clinical data, including demographics, electroclinical features (scalp EEG and invasive monitoring when available), surgical interventions, and postoperative outcomes were extracted from electronic medical records.

Results: Of 23 patients identified, 10 (43%) underwent SEEG as part of their standard care. Seizure outcome data were available for 22 patients in this series. Median post-operative follow-up duration was 3.8 years. Fourteen patients (64%) were seizure-free (Engel 1). Seizure freedom in the SEEG group was 80% (n = 8/10), in comparison to the non-SEEG group (50%, n = 6/12). Success rate was related to complete resection of the regions sampled by SEEG electrodes involved in ictal onset, and a more extensive resection of the lesion (or near total lobectomy).

Significance: Our results underscore the pivotal role of SEEG in enhancing surgical outcomes in patients with drug-resistant epilepsy due to MOGHE. SEEG proved particularly beneficial in defining resection margins, especially in cases where non-invasive data were discordant, scalp EEG patterns were generalized or poorly localized, and imaging findings were nonspecific, diffuse, or normal, making lesion identification challenging.

Objective: To evaluate the long-term cognitive and memory outcomes in patients with drug-resistant temporal lobe epilepsy (TLE) treated with continuous hippocampal deep brain stimulation (Hip-DBS), particularly in individuals not eligible for resective surgery.

Methods: Nine patients (5 female; mean age 37 years) with drug-resistant TLE underwent unilateral or bilateral Hip-DBS via an occipital trajectory. Patients were selected based on bilateral independent seizure onsets, absence of resectable lesions, or high cognitive functioning. All patients underwent comprehensive pre- and post-operative neuropsychological assessments, including the Wechsler Adult Intelligence Scale (WAIS)/Wechsler Intelligence Scale for Children (WISC), Developmental Neuropsychological Assessment (NEPSY), Wechsler Memory Scale, and Rey Auditory Verbal Learning Test (RAVLT). Follow-up ranged from 24 to 121 months (mean: 68 months). Continuous bipolar stimulation was delivered using anterior hippocampal contacts as cathodes and posterior contacts as anodes.

Results: All patients demonstrated significant seizure reduction; four were seizure-free and five were responders (>80% reduction). No morbidity or mortality occurred. Cognitive outcomes remained stable across the cohort. No significant post-operative decline was observed in full-scale, verbal, or performance IQ or memory performance, regardless of unilateral or bilateral stimulation. One patient, with pre-existing major depression, exhibited cognitive decline and reduced memory scores. However, this was attributed to psychiatric deterioration rather than stimulation effects. Her symptoms stabilized following psychiatric treatment, and DBS was reinitiated without further cognitive decline.

Significance: This study provides long-term evidence supporting the cognitive safety and efficacy of continuous Hip-DBS in patients with refractory TLE. Both unilateral and bilateral stimulation were well tolerated, with preserved cognitive and memory function in high-functioning individuals. The findings reinforce the value of Hip-DBS as a non-resective alternative for patients with bilateral or eloquent temporal seizure onsets. Comprehensive psychiatric evaluation and long-term follow-up are critical for optimizing outcomes. Larger, multicenter studies are needed to refine stimulation protocols and better characterize cognitive trajectories.