Epilepsia最新文献

Objective: Although subjective symptoms have received less attention than observable manifestations of functional/dissociative seizures (FDS), patient-reported experiences provide important insights for diagnosis and management. This systematic review summarizes and synthesizes studies describing the subjective symptomatology of FDS and narratively discusses their potential diagnostic value.

Methods: MEDLINE, PsycINFO, and CINAHL were searched from January 1990 to May 2025 for studies reporting qualitative or quantitative data on FDS symptoms. The review was registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD420251008332) and reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Study quality was assessed using Critical Appraisal Skills Programme (CASP) tools. Data were extracted on study design, sample characteristics, data acquisition method, and reported symptoms. Qualitative data were analyzed thematically following Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) principles, whereas quantitative findings were synthesized narratively within the same thematic framework.

Results: Forty-seven studies were included. Subjective symptoms of FDS were highly variable both within and between individuals. Across studies, six broad symptom domains were identified: sensory/pain, arousal, emotional, consciousness-related, cognitive, and motor symptoms. Sensory symptoms (particularly pain and headache), arousal-related symptoms (especially hyperarousal), and emotional symptoms (especially panic and anxiety) were most frequently reported across studies. Symptoms related to altered awareness and dissociation between awareness and responsiveness were described in a smaller number of studies but were more consistently reported as differentiating FDS from epileptic seizures. In contrast, the differential diagnostic value of other subjective symptoms was limited by lack of specificity and insufficient detail regarding context, mode of onset, spread, duration and quality.

Significance: Subjective symptoms in FDS are diverse, but common themes emerge. Detailed descriptions are required to extract differential diagnostic value from subjective FDS symptoms. Future studies should collect structured information about FDS symptoms and study them using systematic, multimodal, and cross-cultural approaches.

Objective: Postictal deficits are a well-recognized phenomenon, yet their mechanisms and predictors remain poorly understood. Distinguishing postictal deficits from recurring nonconvulsive seizures (NCSz) or nonconvulsive status epilepticus (NCSE), their main differential diagnosis, can be challenging. This study aimed to identify clinical and electrographic features predictive of ongoing or recurrent ictal activity and to explore biomarkers associated with the duration and severity of postictal deficits.

Methods: We conducted a retrospective case-control study of patients with prolonged (>1 h) postictal deficits at a tertiary medical center between 2017 and 2022. Based on electroencephalographic (EEG) findings, patients were classified as having uncomplicated Todd's palsy or recurring NCSz. Clinical, imaging, and electrographic characteristics were compared between groups, and factors associated with postictal duration were analyzed.

Results: Among 112 patients, 86 (77%) had uncomplicated Todd's palsy and 26 (23%) had recurring NCSz. Patients with NCSz were younger (63 vs. 76 years, p = .022) and had longer deficits (2.5 vs. 1.5 days, p = .024). Sporadic epileptiform discharges (73% vs. 22%, p < .001) and rhythmic or periodic discharges on the ictal-interictal continuum (50% vs. 16%, p = .001) were significantly more frequent in the NCSE group, even when limited to short EEGs or the first 30 min of continuous EEG (96% vs. 40%, p < .001). Consequently, 2HELPS2B scores were higher in NCSE patients (2 vs. 1, p = .0065). In the uncomplicated Todd's palsy group, a preceding focal to bilateral tonic-clonic seizure (1.5 vs. 1.0 days, p = .04) and any rhythmic or periodic discharges on EEG (3.0 vs. 1.5 days, p = .003) were associated with longer deficit duration.

Significance: A notable minority of patients with prolonged postictal deficits have recurring NCSz. In the absence of reliable clinical or imaging predictors, patients with prolonged deficits may benefit from a 30-min EEG followed-when 2HELPS2B score > 1-by extended continuous EEG monitoring.

Objective: To determine whether there are cognitive consequences of bottom-of-sulcus dysplasia (BOSD) when assessed as adults and whether focal resection of these lesions leads to change in cognition.

Methods: We studied 42 adults, of whom 39 underwent focal resection targeting the lesion. Neuropsychological assessments were tailored to the clinical epileptology.

Results: On average, patients were 30 (15-56) years old at the time of assessment. Epilepsy duration was 21 (3-48) years. Seizure onset ranged between 3 months and 26 years. Fifteen patients (36%) had an age of onset of 12 years or older. Older age of seizure onset correlated with fewer cognitive measures impacted (r = -0.34, p = .026). Frontal (52%) and parietal (33%) lobes were common BOSD locations. Confrontation naming was assessed in 20 patients, 11 (55%) of whom were impaired. Of these 11 patients, 8 (73%) had a left-sided BOSD. Verbal fluency was assessed in 23 patients, 13 (57%) of whom were impaired. Of these 13 patients, 11 (85%) had a frontal BOSD. Processing speed and attention were assessed in 35 patients and deficits were seen in 17% to 20%, though milder reductions were more consistently seen. At post-surgical follow-up (M = 8.07 years, SD = 4.91 years), 59% of patients were seizure free. As a group, there was no evidence of post-surgical cognitive decline after focal resection of the BOSD; processing speed (p < .05) improved post-surgically.

Significance: In adults with BOSD, an earlier age of seizure onset is accompanied by a greater degree of cognitive comorbidity. Naming is commonly affected, particularly for those with left sided BOSDs. Executive dysfunction is common, particularly for patients with a frontal BOSD. Focal lesionectomy is associated with favourable seizure outcome and is cognitively safe with potential for improvement in processing speed.

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.