Acta Epileptologica最新文献

Background: Cognitive impairment (CI) affects approximately one-third of patients with drug-resistant epilepsy (DRE), underscoring the need for accessible predictors. Interictal electroencephalographic (EEG) abnormalities have been proposed as potential indicators of cognitive dysfunction; however, their independent diagnostic utility is unclear. This study aimed to investigate the association between interictal EEG patterns and CI in adults with DRE, with a specific focus on evaluating their incremental predictive value beyond established clinical predictors.

Methods: In this cross-sectional study of 90 adults with DRE were recruited over a six-month period. Participants were stratified into two groups based on their Montreal Cognitive Assessment (MoCA): those with cognitive impairment (Cases; n = 45; MoCA < 26) and those with preserved cognition (Controls; n = 45; MoCA ≥ 26). All participants underwent routine interictal scalp EEG, An EEG recording was classified as abnormal if epileptiform discharges or significant background slowing was identified. The relationships between cognitive status and various clinical variables-including age, monthly seizure frequency and epilepsy type were analyzed using multivariable logistic regression, with expressed as odds ratios alongside their 95% confidence intervals.

Results: The frequency of monthly seizures was significantly higher in the CI group compared to the control group (9.6 ± 2.8 vs. 5.4 ± 2.1 seizures/month, P < 0.001). Interictal EEG abnormalities were also more prevalant in CI group (77.8% vs. 57.8%; OR = 2.56, 95% CI: 1.02-6.41, P = 0.041). However, in the adjusted multivariable model, only seizure frequency reained a signifcant independent association with CI (adjusted OR = 0.46, 95% CI: 0.32-0.65, P < 0.001), indicating that EEG abnormalities did not confer significant additional predictive power after accounting for seizure burden.

Conclusions: Seizure burden emerged as the predominant predictor of CI with DRE, while interictal EEG abnormalities demonstrated a univariate correlation with cogntive status, this association was not independent in the adjusted analysis. EEG findings may still provide contextual or supportive clinical context, emphasize that a comprehensive approach integrating seizure management with cognitive assessments is warranted, rather than relying primarily on interictal EEG for cognitive risk stratification.

Background: To investigate gray matter abnormalities in idiopathic generalized epilepsy (IGE) patients using double inversion recovery (DIR) sequence combined with statistical parametric mapping (SPM).

Methods: We included a total of 31 IGE patients and 31 healthy controls. All participants underwent 3.0T MRI scans of T1WI, T2WI, FLAIR and DIR sequences. In the IGE group, seizure frequency, severity and electroencephalograph performance were recorded in IGE group. Gray matter intensity was analyzed using statistical parametric mapping through individual and group post-processing procedure of DIR images. Spearman analysis and multiple regression analysis were applied for further analysis of clinical factors and regions exhibiting abnormal gray matter intensity.

Results: The individual SPM analysis of DIR images revealed gray matter abnormalities in 15 out of 31 IGE patients, affecting regions including the temporal lobe, frontal lobe, limbic lobe, occipital lobe, brainstem, insular lobe, parietal lobe, thalamus and cerebellum. Intergroup DIR-SPM analysis comparing IGE patients to healthy controls showed a significant increase in gray matter density in the left temporal lobe ( x = -44, y = -56, z = 6, Z score = 4.58, P_FWE = 0.041; x = -48, y = -40, z = -12, Z score = 4.54, P_FWE = 0.047). Generalized spike wave discharges (GSWDs) were positively correlated with the number of voxels exhibiting significantly altered gray matter intensity in each individual with IGE (P_FDR = 0.032). However, the multiple regression model did not identify any significant brain regions influencing the occurrences of GSWDs.

Conclusions: In the IGE group, various regions exhibited alterations in gray matter density according to either individual or group DIR-SPM analysis. The frequency of GSWDs were correlated with the abnormal voxel count across the entire brain cortex of each individual with IGE.

Background: Diagnosing functional seizures can be challenging, and the semiology may vary between pediatric and adult age groups. Identifying those variabilities may be of diagnostic value. This study aimed to compare the semiological characteristics of functional seizures in both the pediatric and adult populations.

Methods: All video ictal electroencephalogram (EEG) recordings at Cairo University Epilepsy Unit (CUEU) from January 2021 to December 2023 were retrospectively reviewed for adults or children with functional seizures. Detailed semiological characteristics of the ictal events were analyzed independently by at least two epileptologists. Each event was listed under the classification system as either major motor, minor motor, dialeptic, non-epileptic aura, or mixed type.

Results: A total of 54 pediatric and 65 adult video ictal EEG studies were evaluated. Minor motor type was the most common clinical semiology among adult and pediatric groups, yet more prevalent in pediatric than adult patients (61.1% vs. 40.0%, P = 0.022). In comparison, the major motor events were significantly higher in adults than in pediatrics (25 event [38.5%] vs. 9 events [16.7%], P = 0.009). No statistically significant differences were found between pediatrics and adults regarding pelvic thrusting (3.7% vs. 9.2%), back arching (7.4% vs. 4.6%), clenched fists (9.3% vs. 15.4%), ictal pain (13.0% vs. 18.5%), ictal fear (5.6% vs. 3.1%), or ictal crying (7.4% vs. 4.6%), respectively.

Conclusions: The semiology of functional seizures varies between pediatric and adult age groups; minor motor events predominate in pediatric patients, while the major motor type is more common in adults.

Background: The temporal lobe is considered as one of the important higher autonomic centers. It has been suggested that autonomic dysfunction could have a potential role in the pathophysiology of sudden unexpected death of epileptic patients (SUDEP). This study aimed to detect autonomic dysfunction in patients with temporal lobe epilepsy (TLE) using different electrophysiological tests and to correlate them with the SUDEP risk.

Methods: This observational case-control study included 27 TLE patients and 27 age- and gender-matched controls. Detailed history and full clinical examination were performed. Brain MRI were done. Electrophysiological studies in the form of sympathetic skin responses (SSR), heart rate variability (HRV), as well as quantitative electroencephalography (QEEG) were performed. SUDEP risk was assessed using the SUDEP-7 inventory scale.

Results: The mean age of the recruited patients was 28.3 ± 8.26 years, with mean seizure duration of 16.59 ± 7.82 years. Epileptogenic lesions were detected in 92.6% of patients, the most common of which was the mesial sclerosis (64%). About 18.6% of the patients achieved seizure control. The patients showed a significantly reduced root mean square of successive differences (RMSSD) at deep breathing (P = 0.003), significantly higher upper limb SSR amplitudes (P = 0.01), and a significantly higher theta band absolute power (TBP) (P = 0.046/0.036). Absolute fronto-central TBP significantly correlated with the SUDEP-7 scores (r = 0.484 and 0.421; P = 0.011/0.029). ROC curve analysis for QEEG showed sensitivity of 75% and 83.3% for Fz and Cz TBP respectively.

Conclusions: Patients with TLE exhibit dysautonomia. Higher TBP as detected by QEEG reflects dysregulation of the higher autonomic centers, which may increase the risk of SUDEP. Thus, QEEG could serve as a sensitive, readily available biomarker for SUDEP risk screening.

Background: Adherence to epilepsy treatment varies greatly and is often compromised by adverse drug reactions. Spontaneous reporting of these reactions has improved pharmacovigilance in many countries. Knowledge, attitudes, and behavior are also key factors influencing treatment adherence. This study aimed to investigate the types of adverse drug reactions in epilepsy, as well as the knowledge, attitudes, and behavior of patients, and how these factors relate to medication adherence.

Methods: This cross-sectional study assessed adverse drug reactions using the Indonesian version of the Liverpool Adverse Event Profile and medication adherence with the Morisky Adherence Questionnaire. Knowledge, attitude and behavior were measured using a self-reported Indonesian knowledge-attitude-behavior questionnaire. Data were collected at two periods of time (2019 and 2022), in which the first period measured adherence, and adverse drug reactions, while the second period measured adherence, and adverse drug reactions, alongside knowledge, attitude, and behavior. Data were gathered from epilepsy patients at the neurology outpatient clinic at Cipto Mangunkusumo National Referral Hospital, and analyzed using Chi-square, likelihood ratio, independent t-test, or Mann-Whitney U Tests, followed by multivariate logistic regression.

Results: Adherence rates in both periods exceeded 50% (50.88% vs. 55.70%). Adverse drug reactions were reported by 78.07% of subjects, and were significantly associated with non-adherence (P = 0.007). The mean knowledge score was 15.41 ± 3.83, and lower knowledge scores were linked to higher odds of non-adherence. Although not statistically significant (P = 0.077), higher knowledge scores showed a trend toward more frequent reporting of adverse drug reactions. Female subjects had higher odds of adherence compared to males (P = 0.013).

Conclusions: Our findings suggest that adverse drug reaction reporting, along with patient knowledge, attitudes, and behavior, are important factors associated with medication adherence. Targeted interventions by healthcare providers to support these areas may help improve adherence in people with epilepsy.

Background: The field of epilepsy neural regulation represented by VNS is rapidly developing. Our aim was to investigate the safety and effectiveness of vagus nerve stimulation (VNS) as an adjunct therapy for pediatric epilepsy in a multi-center study across China.

Methods: Children with epilepsy undergoing VNS as supplementary treatment were consecutively enrolled in this study. Eligibility was limited to children aged 1-16 years with a confirmed epilepsy diagnosis, a stable antiseizure medication regimen, and a minimum of two seizures per 28-day cycle during the 8-week retrospective baseline.

Results: Eighty-seven children (54 males; mean age 8.21 ± 3.88 years, range 0-16) were included, with seizures beginning at an average age of 3.03 ± 2.90 years. A ≥ 50% reduction in seizure frequency was observed in 23.7% at 6 weeks, 20.3% at 10 weeks, 22.6% at 18 weeks, and 18.6% at 26 weeks. Seizure freedom was achieved in 17.1%, 15.9%, 11.3%, and 16.3% of patients at the same intervals. Two subjects experienced adverse events, both of which were mild and transient.

Conclusions: VNS demonstrated moderate efficacy and a favorable safety profile as an adjunct treatment in children with epilepsy. Further large-scale, long-term studies are recommended to confirm these findings.

Background: To provide new insights into the pathological mechanisms of epilepsy associated with variants in the calcium channel voltage-dependent L-type alpha1C subunit gene (CACNA1C, NM_001129837) and to expand the phenotype of CACNA1C-associated neurological disorders: familial mesial temporal lobe epilepsy (FMTLE).

Methods: We conducted a comprehensive analysis of clinical data from a family affected by FMTLE and carried out genetic screening of CACNA1C variants through whole-exome sequencing combined with Sanger sequencing for validation. The clinical characteristics of FMTLE were systematically reviewed, and the pathogenic potential of the identified variant was assessed following the guidelines established by the American College of Medical Genetics and Genomics (ACMG). To explore the underlying pathogenic mechanisms, we utilized bioinformatics tools alongside molecular dynamics simulation methods.

Results: A novel CACNA1C variant (c.5480G > A, p.R1827Q) was identified in a large family with FMTLE. Unlike previous reports, the clinical phenotype of this genotype differs from previous reports, being mild, with focal to bilateral tonic-clonic seizures being more common. Bioinformatics analysis and molecular dynamics simulations indicated that this variant induces local structural changes in the protein.

Conclusions: The findings of this study provide new insights into the complex molecular mechanisms underlying CACNA1C variants and their correlations with patient phenotypes. This research is the first to identify CACNA1C as a potentially new pathogenic gene in FMTLE.

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked seizures that affect approximately 50 million people worldwide. Despite the availability of numerous anti-seizure medicines (ASMs), about 30% of people develop drug-resistant epilepsy (DRE), defined as failure to achieve sustained seizure freedom after trials of two appropriately chosen and tolerated ASM regimens. This population faces significantly reduced quality of life, increased mortality risks, and substantial socioeconomic burdens due to frequent hospitalizations and limited employability.For these treatment-resistant cases, neurostimulation therapies have emerged as promising alternatives to conventional pharmacotherapy. Among these, vagus nerve stimulation (VNS) has become one of the most widely used neurostimulation techniques since approved in 1997. Clinical studies demonstrated that VNS provides meaningful clinical benefits, with approximately 50-60% of patients achieving over 50% reduction in seizure frequency within 12-24 months after implantation. Beyond seizure control, VNS has been associated with improved mood, cognition, and quality of life measures. The therapy is particularly valuable for patients not candidates for resective surgery.This paper presents a comprehensive cost-effectiveness analysis of VNS in DRE by reviewing relevant literature. We examine three key economic dimensions: (1) direct medical costs (including device implantation and maintenance), (2) indirect societal costs (such as productivity loss), and (3) long-term economic benefits. Our analysis reveals that in published papers mostly from developed countries, while VNS requires initial investment, it demonstrated remarkable long-term cost-effectiveness. The therapy significantly reduces healthcare utilization, medication costs, and socioeconomic burdens associated with uncontrolled epilepsy. Furthermore, we identify critical factors influencing cost-effectiveness and propose evidence-based optimization strategies to enhance the value proposition of VNS therapy for diverse healthcare systems and selected patients.

Background: Sodium valproate (VPA) is widely recognized as the first-line treatment for patients with epilepsy (PWE). However, current studies lack evidence to determine the best add-on medication following VPA monotherapy failure. Lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), topiramate (TPM), and carbamazepine (CBZ) also exhibit broad-spectrum activity for seizures. This study aims to compare the therapeutic efficacy of different anti-seizure medication combinations in PWE following valproate monotherapy failure.

Methods: Individuals were categorized into five groups: VPA + LTG, VPA + LEV, VPA + TPM, VPA + OXC and VPA + CBZ. Each group was further subdivided based on seizure type: generalized onset, focal onset, or unknown onset. The effectiveness of these five groups was compared using variance, χ² test and Kaplan-Meier survival analysis.

Results: A total of 2656 PWEs were included in this study. The ≥ 50% response rates for subjects with generalized epilepsy when combining VPA with LTG, OXC, LEV, TPM, and CBZ were 89.6%, 81.0%, 77.9%, 77.7%, and 75.9%, respectively. The LTG group demonstrated significantly higher efficacy than the LEV, TPM, and CBZ groups (P < 0.05). The ≥ 50% response rate of LTG, OXC, LEV, TPM and CBZ for subjects with focal epilepsy were 86.3%, 88.9%, 79.3%, 75.9% and 74.8%, respectively; with the OXC group being significantly more effective than the LEV, TPM, and CBZ groups (P < 0.05).

Conclusions: In this real-world study, we assessed the effectiveness of five anti-seizure medications as add-on therapy for PWE who failed sodium valproate monotherapy. Our findings suggest that combining LTG may be more effective for subjects with generalized epilepsy, while combining OXC may be more effective for subjects with focal epilepsy.

Background: There are increasing incidence of psychiatric side effects associated with the use of anti-epileptics. Prospective observational studies on the effectiveness and safety of levetiracetam (LEV) and brivaracetam (BRV), along with the haematological abnormalities of both treatments, in seizure patients in an Indian population are lacking. Therefore, we aimed to compare the effectiveness and safety of LEV and BRV in seizure patients and evaluated behavioural and non-behavioural side effects, as well as outcomes when switching between LEV and BRV.

Methods: A prospective observational study was conducted in newly diagnosed as well as previously diagnosed patients (n = 115) with epilepsy aged ≥ 5 years of age receiving LEV (n = 66) or BRV (n = 49). Baseline data were collected during the initiation of the study and were compared to the data obtained at the end of the study. A seizure severity questionnaire was used to assess the severity of seizures, and a brief psychiatric rating scale, Hamilton anxiety rating scale, and pediatric epilepsy side effects questionnaire were used to assess the behavioural and non-behavioural side effects.

Results: At baseline, adults taking LEV showed higher rates of behavioral adverse events (BAEs) compared to those on BRV. During follow-up, the most common behavioural adverse event reported in both treatment groups (LEV and BRV) was depression. The most frequently reported non-behavioural side effect in patients taking BRV was drowsiness. Patients who switched from LEV to BRV due to psychiatric side effects showed positive results with BRV (n = 5).

Conclusions: In summary, the study found that BRV is a safe alternative, with fewer and less severe side effects compared to LEV. While LEV showed slightly higher efficacy and a lower probability of drowsiness, BRV proved more tolerable for patients experiencing LEV-induced side effects. Switching from LEV to BRV decreased the psychiatric side effects.