Epilepsia最新文献

Objective: The purpose of the study was to evaluate the usefulness and reliability of the Russian versions of the Global Assessment of Disability Related to Seizures (GADS) and Global Assessment of Severity of Epilepsy (GASE), as Patient-Reported Outcomes Measures (PROMs), among patients with epilepsy (PWE) in the Russian population. Additionally, we aimed to identify predictors of seizure-related disability and epilepsy severity in our patients.

Methods: Data from 186 adult PWE consecutively enrolled in the outpatient clinic of the Moscow Research and Clinical Center for Neuropsychiatry were used to assess the validity of the scales. Clinical and demographic data were collected. Patients completed the GADS and GASE scales and a range of other measures (Neurological Disorders Depression Inventory for Epilepsy, Epilepsy Anxiety Survey Instrument-brief version, Quality of Life in Epilepsy Inventory-31, EpiTrack, Epilepsy Stigma Scale) to assess the psychometric properties of the scales. Multiple linear regression models were developed to identify predictors of patient-reported disability from seizures and epilepsy severity.

Results: Both GADS and GASE demonstrated convergent validity, known-groups validity, and construct validity. The most significant predictors of GADS score included the frequency of seizures, achieving 1-year seizure freedom, official disability status, employment status, stigma, and anxiety. The main predictor of GASE scores was self-reported disability due to seizures (GADS), followed by quality of life, frequency of seizures, stigma, and cognitive function.

Significance: The study confirmed the validity and usefulness of the Russian versions of the GADS and GASE scales, which can be used in both clinical and research settings.

Objective: Status epilepticus (SE) is the most severe expression of seizures, encompassing both SE with prominent motor symptoms and nonconvulsive SE (NCSE). Ictal-interictal continuum (IIC), an electroencephalographic phenomenon, is characterized by periodic discharges (PD), spike-and-waves or sharp-and-waves (SW), or lateralized rhythmic delta activity (LRDA). Peri-ictal magnetic resonance imaging (MRI) abnormalities (PMA) may offer a potential surrogate marker for ictal activity, yet their association with IIC remains unclear. We aimed to investigate the occurrence of PMA in patients with SE and IIC, and to determine the relationship between IIC patterns and PMA through a latent cluster analysis (LCA).

Methods: In a prospective cohort study, 223 adult patients diagnosed with SE or IIC underwent electroencephalography (EEG) and MRI within 48 h of diagnosis. Patients were stratified into two groups: the IIC group and SE group. PMA were assessed using the following MRI sequences: diffusion-weighted imaging, fluid-attenuated inversion recovery, and arterial spin labeling. LCA was performed to identify classes based on etiology, EEG patterns, and their localization.

Results: PMA were as frequent in patients of the IIC group (23/49, 47%) as in patients of the SE group (64/149, 43%, p = .37). In the IIC group, peri-ictal hyperperfusion was more frequently associated with lower frequency PD/SW (.5-1 Hz; 12/19, 63%), followed by LRDA (4/13, 31%) and higher frequency PD/SW (>1-2.5 Hz; 4/17, 24%). LCA revealed two classes; Class 1, characterized by nonunilateral high-frequency PD/SW and triggering factors in epilepsy, had fewer PMA (18%) as compared to Class 2, characterized by predominantly unilateral low-frequency PD/SW and diverse etiologies (50%; odds ratio = 5.79, p = .02).

Significance: PMA occurrence in IIC aligned closely with that in SE, suggesting an overlap between IIC and SE and raising the critical question of whether patients with IIC may have NCSE. We propose an etiology-driven approach for EEG interpretation in IIC, which may enhance diagnostic accuracy and treatment strategies.

Objective: Lamotrigine is one of the most widely prescribed antiseizure medication (ASM) and mood stabilizer in the United States due to its favorable side-effect profile, lower risk of teratogenicity, and minimal drug-drug interactions. This study aimed to examine age- and sex-associated variability in prescribing and pharmacokinetics, focusing on postmenopausal women.

Methods: Data were from electronic health records. Individuals were included if ≥18 years and received an ASM between January 1, 2015 and December 31, 2021. Lamotrigine prescriptions were compared based on age, sex, epilepsy diagnosis, and monotherapy/polytherapy. Statistical comparisons of proportions were conducted using two-proportion tests. To characterize age- and sex-related differences in LTG apparent oral clearance and assess the impact of covariates, linear mixed-effects modeling was employed.

Results: Records were available for 314 890 individuals, with 23 906 patients being prescribed lamotrigine at least once (as monotherapy or polytherapy) for both epilepsy and non-epilepsy diagnoses. The lamotrigine prescription rate was lower in postmenopausal women compared to younger women but higher than in older men, irrespective of diagnosis. Notably, lamotrigine was prescribed as monotherapy more frequently to patients without epilepsy than those with epilepsy, regardless of sex and age. The clearance of lamotrigine was 22% lower in postmenopausal women compared to younger women and 9% in older men. Lamotrigine clearance increased by 49% and 11% with co-administration of inducers or the presence of smoking, respectively. Lamotrigine clearance decreased by 51% in the presence of an inhibiting medication.

Significance: Prescription rates for lamotrigine varied between patients with epilepsy and those with non-epilepsy conditions. Age and sex differences in pharmacokinetics suggest the need for lamotrigine dose adjustments, highlighting the importance of therapeutic drug monitoring in personalized epilepsy care. Lamotrigine use was less frequent in postmenopausal women compared to younger women but higher compared to older men. Postmenopausal women were prescribed lamotrigine as monotherapy to a lesser extent than younger women and older men.

Objective: Dravet syndrome (DS) is the prototypic developmental and epileptic encephalopathy, characterized by drug-resistant seizures, developmental slowing, and many other morbidities. Detailed characterization of behavioral phenotypes and social-emotional skill development are limited.

Methods: We prospectively assessed behavioral and social-emotional problems in the ENVISION natural history study (NCT04537832) of children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at <5 years of age. Assessments every 3 months for up to 2 years included the Child Behavior Checklist (CBCL), Strengths and Difficulties Questionnaire (SDQ), Brief Infant-Toddler Social and Emotional Assessment (BITSEA), and Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3).

Results: Fifty-eight children with DS enrolled at 16 sites worldwide. Problematic behaviors-inattention, aggressive or oppositional behaviors, and withdrawn and autistic behaviors-began before age 3 years, became more evident with age, and were clinically significant in many children by age 3-4 years. CBCL Total, Externalizing, and Internalizing Problems T-scores rose by approximately 3 points per year, and BITSEA Problem scale scores increased by 2.3 points annually (p = .002). SDQ Hyperactivity scores worsened over time (p = .013), whereas emotional difficulties remained stable. VABS-3 Socialization domain scores, which were already more than 1 SD below the normative mean at baseline, decreased further, particularly in younger participants. Correlation analyses showed that poorer communication abilities were associated with increased problematic behaviors (R = -.55 for CBCL Total Problems and VABS-3 Communication scores). Mixed-effects modeling identified age as the strongest predictor of worsening behavioral outcomes.

Significance: We found that behavioral and social-emotional problems are inherent components of DS that present in toddlerhood and worsen throughout early childhood. This highlights the need to diagnose and manage these issues early. Targeted therapy may alleviate the wide-ranging morbidities that are intrinsic to DS, including the social-emotional and behavior problems that frequently emerge.

Objective: In epilepsy, daily treatment provides only symptomatic seizure control, leaving a significant unmet need for a treatment that affects the underlying predisposition to seizures. Here, in a first-of-its-kind study, we test the hypothesis that intermittent treatment of seizure clusters with diazepam in the kainic acid post-status epilepticus rat model of acquired epilepsy has an enduring effect on the seizure cluster phenotype, suggestive of potential disease modification.

Methods: Following kainic acid-induced status epilepticus, rats with epilepsy were monitored for occurrence of seizure clusters (≥2 seizures in 24 h) for a 3-week baseline period before entering a 6-week treatment period using a previously established multidose regimen of diazepam (n = 7) or vehicle (n = 9) upon identification of a seizure cluster. In a subsequent 2-week outcome period during which no rats received diazepam, we evaluated changes in seizure cluster size, burden (cluster size × severity), duration, and other phenotype parameters.

Results: A total of 3396 seizures and 216 seizure clusters were included for analysis. During the outcome period, time between seizures in a cluster (also interseizure interval [ISI]) was significantly longer in the diazepam group (log ISI = .25 longer, SE = .08, p < .0001), and the proportion of clustered seizures with an ISI of ≤30 min increased in the outcome period in the vehicle group (p = .023) but was stable in the diazepam group. Despite the occurrence of rebound seizures during the treatment period, improvement in several phenotypical parameters, including severity and proportion of seizures in a cluster, supported a positive impact of intermittent diazepam treatment on seizure cluster biology.

Significance: Changes in several seizure cluster phenotypical parameters were suggestive of an enduring disease-modifying effect of diazepam, despite an apparent rebound effect of intermittent diazepam treatment on seizure frequency. Further study is warranted using a model incorporating a background antiseizure medication regimen to potentially attenuate the unexpected rebound seizures.

Objective: Responsive neurostimulation (RNS) offers an effective and safe treatment for people living with refractory focal-onset epilepsy. Many RNS candidates need intracranial electroencephalography (IEEG) monitoring to locate seizure-onset zones (SOZs), which is a difficult procedure with variable yields. High-frequency oscillations (HFOs) are a common ictal-onset feature, and our study seeks to explore ictal HFOs as a marker for targeting RNS.

Methods: We screened patients who underwent IEEG then RNS implantation at our center from 2015 to 2022. While blinded to outcomes, we analyzed IEEG using standard clinical software to detect ictal HFO-onset patterns at the previously identified onsets. Then we examined RNS lead placement in relation to the SOZs and seizure control outcomes after 2 years post-implantation.

Results: A total of 62 patients received RNS during the study period. Excluding those patients with insufficient follow-up and combined surgeries (RNS + resection/ablation), 33 patients remained. At 2 years, 26 (~78.8%) had ≥50% seizure reduction, and 7 (~21.2%) were free of debilitating seizures (super-responders). We excluded an additional 8 patients due to having skipped IEEG and early explantation, leaving 25 study subjects. Ictal HFOs were present in all SOZs for 17 patients, and 14 patients (including all 7 super-responders) had RNS leads implanted in all of these SOZs. When ictal HFOs were absent or not covered by RNS leads, the patients did not achieve seizure freedom. There was a statistically significant association between targeting SOZs with ictal HFO onsets and outcomes (Fisher's exact test p-value 0.0078).

Significance: Our results suggest that ictal HFOs provide additional localization value. Ictal HFOs represent very local epileptiform activity that may reflect closer proximity to epileptogenic tissue than conventional features such as spiking and slower rhythms. Because stimulation acts by focal tissue activation, increased targeting precision may be more important in RNS than surgeries such as resection or ablation.

Objective: The US Food and Drug Administration (FDA) issued a warning that lamotrigine slows cardiac conduction, leading to arrhythmias in people with heart disease (HD). This is the first study to investigate the within-person changes in electrocardiographic (ECG) metrics and prevalence of ECG abnormalities when on versus off lamotrigine, in people with and without a history of HD.

Methods: The cohort includes 237 people with ECG both on and off lamotrigine, stratified by a history of HD (n = 97). The within-person percent change in heart rate and ECG metrics (PR, QRS, and heart rate-corrected QT [QT_c] intervals) on versus off lamotrigine is compared within and between groups. Linear mixed effect regression models with adjustments for covariates assess the association between within-subject changes in ECG metrics and pathologies when on versus off lamotrigine.

Results: PR interval (atrioventricular conduction) is significantly longer on- versus off lamotrigine (mean = 3.1% increase). There is a significant increase in the PR within the no HD (3.5%), all HD (2.8%), and structural HD groups (4.1%) when on versus off lamotrigine, but there is no difference between groups. Regression models confirm that lamotrigine is associated with an increase in PR interval in the overall cohort, as well as those with and without HD. Lamotrigine is not associated with an increased prevalence of clinically pathological PR, QRS, or QT_c prolongation, or abnormal ECG interpretations. Subanalysis in people with lamotrigine serum levels in the therapeutic range indicate that each 1-μg/mL increase in concentration is associated with a 2.3% increase in PR interval.

Significance: Lamotrigine leads to an increase in PR interval in the general population and people with HD (population in FDA warning). However, lamotrigine is not associated with increased odds of PR prolongation or any ECG abnormalities. Despite in vitro data predicting cardiac ECG abnormalities, particularly in people with HD, lamotrigine is not associated with the development of pathological ECG findings.

Objective: Antiseizure medication (ASM) may affect autonomic nervous system (ANS) activity in patients with epilepsy (PWE). We examined the relationship between ASM dosage and multimodal correlations among ANS signals recorded from wearables in pediatric PWE.

Methods: We evaluated evening (ASM intake from 5 p.m. to 3 a.m.) multimodal recordings (heart rate [HR], electrodermal activity [EDA], temperature [TEMP], and respiratory rate [RR]) from wearables (Empatica E4) worn by pediatric PWE during long-term monitoring at Boston Children's Hospital between 2015 and 2021. Within-patient comparisons were performed in two groups: patients with both high- and no-dose ASM days, and with both high- and low-dose ASM days. Multimodal interactions were assessed using principal component and canonical correlation analysis, and repeated measure analyses of variance with time and dose as factors.

Results: Of the 52 patients (median age = 12.8 years), 34 total patients had both high- and low-dose ASM days, and 24 total patients had both high- and no-dose days. An interaction between dose and time emerged in the high- versus no-dose comparison (p = .002), indicating divergent trajectories of multimodal autonomic correlations across medication states; correlations increased on high-dose days and decreased on no-dose days. EDA increased (p = .003) and HR decreased (p = .036) from baseline to peak window for patients with both high- and low-dose days. No time effects or dose-time interactions were found for TEMP and RR. Subanalyses by ASM mechanism of action showed no differential effects on individual ANS measures. Cox modeling showed a dose effect on time to seizure (chi-squared = 6.98, p = .031), with higher hazard on low- versus high-dose days (p < .01) and no difference between no- and high-dose days (p = .626).

Significance: ASM dosage was related to multimodal autonomic correlations, suggesting central autonomic regulation and seizure vulnerability. Wearable-based monitoring of these correlations could support seizure risk assessment and inform personalized treatment strategies.