High Seizure Frequency Research Articles

Systematic literature review of the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures in adults.

This systematic literature review (SLR) assessed the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures (PGTCS) in adults to evaluate these domains in both populations and identify evidence gaps to inform future research. A search was conducted on December 7, 2022, using MEDLINE and Embase to identify studies published from 2012 onwards reporting humanistic burden (patient-reported or caregiver-reported outcomes or utilities, qualitative evaluations), economic burden (productivity loss, caregiver and societal costs of epilepsy), and sleep-related outcomes. Of the 2830 citations identified, 136 were included. Most studies were in the focal epilepsy population; very few studies reported outcomes in the PGTCS population. The presence of epilepsy-specific instruments varied based on the domain evaluated. Epilepsy exerted considerable humanistic and economic burden. Indicators of poor disease control (e.g., high seizure frequency, resistance to anti-seizure medications, polypharmacy) increased epilepsy burden. Seizure frequency and type, disease severity, and polypharmacy also affected work productivity. Adults with epilepsy, particularly focal epilepsy, reported higher indirect costs, more sick days accrued, and early entry into retirement. Caregivers similarly reported high productivity loss and absenteeism related to caregiving duties. The results of this SLR highlight the high humanistic and economic burden of focal epilepsy and PGTCS, although limited data were available for the PGTCS population. The results include patient-reported outcome data specific to focal epilepsy and PGTCS, expanding the limited humanistic burden evidence identified in previous reviews, and show the effect of poor disease control on individuals' lives and as a driver of indirect costs. PLAIN LANGUAGE SUMMARY: Our systematic literature review identified studies that evaluated the impact of focal epilepsy and primary generalized tonic-clonic seizures on patients and their caregivers. We found that focal epilepsy negatively impacted patients' mental health and sleep and was associated with higher indirect costs and lower work productivity in people with more severe disease. The impact of primary generalized tonic-clonic seizures on patients was rarely reported, and future research is needed.

Optimizing electroencephalogram duration for efficient detection of epileptiform abnormalities in diverse patient groups: a retrospective study

BackgroundThere is no standardized EEG duration guideline for detecting epileptiform abnormalities in patients, and research on this topic is scarce. This study aims to determine an optimal EEG duration for efficient detection of epileptiform abnormalities across different patient groups.MethodsRetrospective analysis was performed on EEG recordings and clinical data of patients with the first seizure and epilepsy. Patients were categorized based on various factors, including the interval time since the last seizure, use of anti-seizure medication (ASM), and seizure frequency. The detection ratio (DR) of epileptiform abnormalities and latency time for their discovery were calculated. Statistical analyses, including chi-square tests, logistic regression, and survival analysis were utilized to illustrate DR and latency times.ResultsIn whole-night EEG recordings, the DR was 37.6% for the first seizure group and 57.4% for the epilepsy group. Although the maximum latency times were 720 min in both two groups, DR in the first seizure group was distinctly decreased beyond 300 min. Significant factors influencing the DR included the use of ASM in the first seizure group (P < 0.05) and seizure frequency in the epilepsy group (P < 0.001). For epilepsy patients who experience a seizure at least once a month or undergo timely EEG recordings (within 24 h after a seizure), the DR significantly increases, and the maximum latency time is reduced to 600 min (P < 0.001). Additionally, the DR was significantly reduced after 240 min in epilepsy patients who had been seizure-free for more than one year.ConclusionsIn this retrospective study, we observed a maximum latency of 720 min for detecting epileptiform abnormalities in whole-night EEG recordings. Notably, epilepsy patients with a higher seizure frequency or timely EEG recordings demonstrated both a higher detection ratio and a shorter maximum latency time. For patients exhibiting a low detection ratio, such as those experiencing their first seizure or those with epilepsy who have been seizure-free for more than a year, a shorter EEG duration is recommended. These findings underscore the importance of implementing customized EEG strategies to meet the specific needs of different patient groups.

Long-term outcomes and adaptive behavior in adult patients with Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy characterized by difficult-to-control seizures and cognitive dysfunction. Previous studies mainly focused on pediatric populations, and little is known about the long-term cognitive outcome in adult patients with LGS. The objective of this study was to investigate the long-term functional and adaptive behavior in adult patients with LGS. This cross-sectional study enrolled adult patients diagnosed with LGS according to the recently published International League Against Epilepsy (ILAE) diagnostic criteria. The adaptive behavior of participants was assessed using the Vineland Adaptive Behavior Scales, Survey Interview, Second Edition (VABS-II). Demographic, clinical, electroencephalography (EEG), and antiseizure medication (ASM) data were also collected at different timepoints, to investigate their association with VABS-II scores. The study included 38 adult patients with LGS. A low score on the Adaptive Behavior Composite Scale was found in all patients. When considering single VABS-II domains, particularly low scores were found in daily living skills and socialization, whereas slightly higher performances were observed in communication. An earlier age at LGS diagnosis was identified as the most significant predictor of worse adaptive outcomes in adult life. At the time of study evaluation, high seizure frequency, higher EEG background slowing, and multifocal EEG epileptiform abnormalities were significantly associated with lower VABS-II raw scores. Furthermore, in an exploratory correlation analysis with ASM regimen at the study visit, treatment with cannabidiol was associated with higher adaptive behavior scores, whereas benzodiazepine intake correlated with lower scores. This study provides relevant insights into the long-term challenges faced by adults with Lennox-Gastaut syndrome (LGS), highlighting significant impairments in adaptive behavior as well as the associated clinical and electroencephalography features. Additionally, this study provides a more specific neuropsychological profile in adults with LGS and underscores the importance of comprehensive care approaches that go beyond seizure control in this population. This study examined adults with Lennox-Gastaut syndrome (LGS), a severe type of epilepsy, to understand their long-term abilities to perform daily tasks and adapt socially. We found that these adults have significant difficulties with daily living and social skills, although not all areas were equally affected. They performed somewhat better in communication, particularly in understanding others (receptive communication). Importantly, the younger the age at which LGS was diagnosed, the worse their outcomes were as adults. This study highlights the need for research and treatment approaches that focus not only on controlling seizures but also on improving daily life skills.

Neurofilament light (NfL) concentrations in patients with epilepsy with recurrent isolated seizures: Insights from a clinical cohort study

PurposeTo detect possible neuronal damage due to recurrent isolated seizures in patients with epilepsy in a clinical routine setting. MethodsWe measured the serum concentrations of neurofilament light chain (sNfL) in 46 outpatients with an at least monthly occurrence (self-reported) of generalized tonic-clonic seizures in the six months prior to the study and in 49 patients who had been seizure free (self-reported) for at least one year. We assigned the patients with seizure activity into groups with moderate and high seizure frequency. We measured sNfL with a highly sensitive single molecule array (Simoa). ResultsThe majority (94 %) of all patients with epilepsy had sNfL values within the age adjusted reference ranges of our laboratory. Three patients with and three patients without seizure activity (each 3 %) showed elevated sNfL concentrations. Age adjusted sNfL concentrations did not differ significantly between patients with and without seizure activity in the total sample or in the female subgroup. In contrast, NfL concentrations were significantly higher in male patients with seizure activity and highest in the subgroup of those with high seizure activity, but were only above the reference range in two patients. sNfL concentrations did not differ between focal and generalized epilepsies and between genetic and structural etiologies. ConclusionsThe sNfL concentrations in patients with epilepsy and healthy patients did not differ significantly. The finding of higher sNfL concentrations in males with self-reported seizure activity should be viewed with utmost caution because the difference was small and only two male patients showed sNfL concentrations above the reference range.

Epilepsy in inmate patients seen in a high complexity reference hospital in Colombia: A cross-sectional study.

To describe the sociodemographic and clinical characteristics of imprisoned patients with epilepsy seen at Samaritana University Hospital (HUS) in Bogotá D.C., between January 2017 and November 2020. Cross-sectional cohort study of inmate patients over 18 years of age seen at HUS between January 2017 and November 2020, with a discharge diagnosis of epilepsy. A descriptive univariate analysis of patient sociodemographic and clinical characteristics was carried out. Overall, 92 patients were included, 95.7% were males with a median age of 32 years (IQR: 26-44); 65% were assessed in the outpatient clinic; median hospital length of stay was 2 days (IQR: 0) and 7.6% required admission to the intensive care unit; 75% had focal onset epilepsy, 63.04% with undetermined etiology 31.52% with structural causes. Polytherapy was found in 53.3%, valproic acid being the most frequently used antiseizure medication in 59.78%; lack of adherence was reported in 15.22% and inadequate seizure control in 81.52%; status epilepticus occurred in 5.34%. A total of 31 EEG recordings and 53 brain images were performed, of which, 29% and 39.62%, respectively, were abnormal. Non-epileptic paroxysmal events were diagnosed in 5.34%, while organic or psychiatric comorbidities were found in 25%, and the use of psychoactive substances was documented in 17.39%. Upon discharge, 93.47% had no disability, and only 45.65% returned for outpatient follow-up. The clinical profile was of men in the fourth decade of life with focal onset epilepsy characterized by high seizure frequency, most of whom were receiving antiseizure medication, with a high proportion of polytherapy. The results are a point of departure for prospective studies designed to identify points to intervene and improve healthcare for inmates with epilepsy. Inmates are a vulnerable proportion of persons with epilepsy. In this group there are significant differences compared to the general population, especially with greater psychiatric comorbidity and worse control of epileptic seizures due to difficulties in accessing medical care, antiseizure medication and diagnostic tests. We found that the most characteristic population is made up of men in the fourth decade of life with a high frequency of seizures, most of whom were receiving multiple antiseizure medication This study is the first of its kind in Latin America and it is an initial approach to epilepsy in inmates.

Mortality of epilepsy in Chinese populations: a comprehensive review.

Premature mortality is a significant part of the epilepsy burden and may vary across populations, especially between high-income and lower- and middle-income countries. People with epilepsy in China are approximately a fifth of the global population with epilepsy. Previous studies were unlikely to represent the situation in China due to limitations in design, methods, sample size, follow-up time, and other inherent population heterogeneity. By summarising the evidence on the mortality characteristics in Chinese populations with epilepsy in the last six decades, we found a median mortality rate of 14.7 (6.8-74.4)/1000 person-years and a median standardised mortality ratio (SMR) of 4.4 (2.6-12.9) in population-based studies, and a median mortality rate of 12.3 (9.5-101.5)/1000 person-years and a median SMR of 3.0 (1.5-5.1) in hospital-based studies. Vascular diseases, complications of diabetes, and accidental injuries were the leading causes of death. Risk factors for mortality were reported as older age, male, longer duration and higher frequency of seizures. Case fatality ratios of status epilepticus (SE) in adults were higher than in children, and both increased with follow-up time. Mortality in people with symptomatic epilepsy was high and varied across different primary diseases. The highest mortality rate and sudden unexpected death in epilepsy (SUDEP) incidence were reported from the least developed areas in China. Accidental injuries were the most common causes of epilepsy-related deaths, while the incidence of SUDEP may be underestimated in Chinese populations. Further research is warranted to improve the understanding of premature mortality risk so that preventative measures can be introduced to improve the situation.

Application of Mozart's Sonata for Two Pianos in D Major in Children with Epilepsy and Effect of Acoustic Quality on Epileptic Discharges.

Mozart's Sonata for Two Pianos in D Major (K448) is a classic double piano work. This study investigated its effect on children with epilepsy (EP) and analyzed the changes in electroencephalography (EEG) among children on the basis of acoustic quality. The clinical data of 150 children with EP in the Affiliated Hospital (Group) of Putian University from March 2020 to March 2023 were retrospectively analyzed. They were divided into group A (n = 73, antiepileptic drug therapy) and group B (n = 77, antiepileptic drug therapy + Mozart K448) in accordance with the treatment methods. The seizure frequency, frequency of epileptic discharges (EDs), and Quality of Life in Childhood Epilepsy Questionnaire-16 in both groups were compared before and after treatment. The changes in EEG before, during, and after music appreciation were observed. The effects of the acoustic characteristics (rhythm, root mean square value, roughness, and spectral flux) of Mozart K448 on EDs in children were explored. After treatment, group A had a higher seizure frequency (P < 0.001), a higher frequency of EDs (P < 0.05), and significantly lower scores of cognition and emotion than group B (P < 0.001), without significant difference in the scores of social function and physical function (P > 0.05). The frequency of EDs before music appreciation was significantly higher than that during music appreciation (P < 0.01). Spearman correlation analysis showed that the rhythm, spectral flux, and roughness in Mozart K488 were related to the decrease in EDs among children with EP (P < 0.001). This study confirmed the application effect of Mozart K448 in children with EP. Mozart K448 can decrease the seizure frequency, reduce the ED occurrence, and improve the quality of life. The acoustic characteristics of K448 may be the reason for improving EP in children.

Determinants of successful ictal SPECT injection in phase 1 epilepsy presurgical evaluation: Findings from the pediatric epilepsy research consortium surgery database project.

The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests available, ictal single-photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri-ictal radionuclide administration. Recent studies indicate that geographic and center-specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri-ictal injection during inpatient admission) using surgery-related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center-specific hours of SPECT availability would increase the likelihood of successful ictal SPECT. We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center-specific SPECT practices. Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non-Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre-admission protocols prior to VEEG (p = 0.002). There is inter-center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non-Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection. In pediatric patients with drug-resistant epilepsy, single-photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half-life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center-specific factors and patient-specific factors associated with an ictal SPECT injection in the first, pediatric-focussed, large-scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center-specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient-specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.

Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy.

Although Coronavirus disease 2019 (COVID-19) vaccinations are generally recommended for persons with epilepsy (PwE), a significant vaccination gap remains due to patient concerns over the risk of post-vaccination seizure aggravation (PVSA). In this single-centre, retrospective cohort study, we aimed to determine the early (7-day) and delayed (30-day) risk of PVSA, and to identify clinical predictors of PVSA among PwE. Adult epilepsy patients aged ≥18 years without a history of COVID-19 infection were recruited from a specialty epilepsy clinic in early 2022. Demographic, epilepsy characteristics, and vaccination data were extracted from a centralized electronic patient record. Seizure frequency before and after vaccination, vaccination-related adverse effects, and reasons for or against vaccination were obtained by a structured questionnaire. A total of 786 PwEs were included, of which 27.0% were drug-resistant. At the time of recruitment, 74.6% had at least 1 dose of the COVID-19 vaccine. Subjects with higher seizure frequency (p < 0.0005), on more anti-seizure medications (p = 0.004), or had drug-resistant epilepsy (p = 0.001) were less likely to be vaccinated. No significant increase in seizure frequency was observed in the early (7 days) and delayed phases (30 days) after vaccination in our cohort. On the contrary, there was an overall significant reduction in seizure frequency 30 days after vaccination (1.31 vs. 1.89, t = 3.436; p = 0.001). This difference was seen in both types of vaccine (BNT162b2 and CoronaVac) and drug-resistant epilepsy, but just missed significance for the second dose (1.13 vs. 1.87, t = 1.921; p = 0.055). Only 5.3% had PVSA after either dose of vaccine. Higher pre-vaccination seizure frequency of ≥1 per week (OR 3.01, 95% CI 1.05-8.62; p = 0.04) and drug-resistant status (OR 3.32, 95% CI 1.45-249 7.61; p = 0.005) were predictive of PVSA. Meanwhile, seizure freedom for 3 months before vaccination was independently associated with a lower risk of PVSA (OR 0.11, 95% CI 0.04-0.28; p < 0.0005). This may guide epilepsy treatment strategies to achieve better seizure control for at least 3 months prior to vaccination. As COVID-19 shifts to an endemic phase, this study provides important data demonstrating the overall safety of COVID-19 vaccinations among PwE. Identification of high-risk patients with subsequent individualized approaches in treatment and monitoring strategies may alleviate vaccination hesitancy among PwE.

Disability burden of epilepsy in Türkiye: How does it differ from other newly industrialized countries?

IntroductionEpilepsy accounts for a substantial part of the global burden of disability. This study aimed to investigate the employment history of people with epilepsy in Türkiye, evaluate the role of education level in employment and epilepsy burden, and compare epilepsy employment data in different societies according to sociodemographic index data. MethodsThis prospective study included 420 people 16–76 years of age who were diagnosed with epilepsy according to the criteria of the International League Against Epilepsy. Socioeconomic, clinical, and employment data were collected using a questionnaire in face-to-face interviews. ResultsThe study sample was 52 % women, the mean age was 34.2 ± 12.7 years (range: 16–76 years), and the mean disease duration was 17.2 ± 12.6 years. Only 26.7 % (n = 112) of the participants were actively working, 38.8 % had never worked, and 64.5 % had changed jobs at least twice (mean 2.45 job changes). The unemployment rate among the study sample was 7 times higher than in the general population. Female gender, low self and parental education levels, high seizure frequency, and the use of multiple anti-seizure medications were significantly associated with lower employment. ConclusionWe determined that the employment rates and education levels of people with epilepsy in Türkiye are low, the unemployment rate is high, and the burden of epilepsy is higher when compared with other low-middle income and newly industrialized countries and national population data. Education and employment opportunities for people with epilepsy in Türkiye should be improved to reduce the burden of epilepsy-related disability and thereby increase quality of life, welfare, and psychosocial well-being in this group.

Physical fitness in Indian women with epilepsy on anti-seizure medications and its association with reproductive status, quality of life and stigma: A cross-sectional study

PurposeTo determine the status of physical fitness, reproductive abnormalities, QOL and epilepsy associated stigma in women with epilepsy (WWE) and their association with ASM therapy and seizure frequency. MethodsThis cross-sectional study included WWE of reproductive age (18–50 years) on antiseizure medications (ASMs) for at least three months before enrolment. Physical fitness was assessed using International Physical Activity Questionnaires (IPAQ) and Body composition analysis. Subjects were interviewed for menstrual abnormalities [menstrual disturbance or Polycystic Ovary Syndrome (PCOS)/hirsutism]. Validated questionnaires were used for assessment of, QOL (QOLIE-10) and Stigma in epilepsy (Epilepsy Stigma Scale). Sub-group analysis was done to compare the above parameters on the basis of a) type of therapy (mono or polytherapy), b) type of ASMs treatment (conventional, newer, or conventional + newer ASMs), and c) seizure type and (d) seizure frequency. Correlation and regression analysis were done to find out the association among different variables with physical fitness. ResultsThe overall prevalence of poor physical fitness, reproductive abnormalities, worsened QOL and stigma in the enrolled WWE (n = 203) were 21.18 %, 20.19 %, 52.7 %, and 21.67 %, respectively. Sub-group analysis revealed that WWE on monotherapy (n = 99) had higher median IPAQ score (p = 0.002), comparatively less reproductive abnormalities (24.03 %, p = 0.008), and higher stigma (24.03 %, p = 0.04) than polytherapy group. WWE on conventional ASMs had significantly higher IPAQ scores compared to newer and conventional + newer ASMs groups (p = 0.02). The prevalence of poor physical fitness and stigma was significantly higher in WWE with higher number of seizures (p = 0.007, <0.001, respectively). No significant difference in QOL was observed on the basis of ASM type and therapy; however, WWE with generalized onset seizures had worsened QOL compared to those with focal onset seizures (p = 0.04). A significant negative correlation was found among seizure frequency and IPAQ score in WWE (p = 0.04). ConclusionWWE on polytherapy were physically less active, higher occurrence of reproductive abnormalities, and stigma compared to the monotherapy group. WWE with higher seizure frequency had poor physical fitness, and higher stigma compared to those with lesser number of seizures. These findings may aid value in optimization of ASM treatment in WWE of reproductive age.

Association of Clinical, Tumor, and Treatment Characteristics With Seizure Control in Patients With IDH1/2-Mutant Lower-Grade Glioma.

Patients with IDH1/2-mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics and the impact of surgery and adjuvant treatments (AT) on seizure control along the disease trajectory. We retrospectively included patients with IDH1/2-mutant lower-grade glioma who underwent surgery at the neurosurgery divisions of the University of Turin and Milan and were treated at the Division of Neuro-Oncology of Turin. Inclusion criteria were a diagnosis according to the 2021 WHO Classification and presentation with seizures; exclusion criteria were presence of CDKN2A/B homozygous deletion, intense/ring contrast enhancement on MRI at presentation, and small tissue biopsy. We evaluated seizure freedom for 2 months after surgery, 6 months from starting observation or AT, at recurrence, and for 6 months after treatments of recurrence. We included 150 patients. There were 77 (51%) and 31 (21%) patients with IDH-mutant/1p19q-codeleted grade 2 and 3 oligodendroglioma and 30 (20%) and 12 (8%) with IDH-mutant grade 2 and 3 astrocytoma, respectively. Total resection was accomplished in 68 (45%). Seventy-five patients (50%) received AT while the remaining 75 were observed with MRI. After 6 months after AT, 28 of 29 patients (96.5%) displayed seizure reduction, 5 of 28 (18%) being seizure-free. 66 of 124 patients (53%) had seizures at recurrence. After 6 months after second-line treatments, 60 of 66 patients (91%) had seizure reduction, 11 (17%) being seizure-free. In multivariable analyses, grade 3 histology positively correlated with seizure freedom at 2 months after surgery (OR 3.5, 1.4-8.9, p = 0.008), 6 months after AT (OR 9.0, 1.5-54.9, p = 0.017), and 6 months after treatment of recurrence (OR 4.9, 1.5-16.5, p = 0.009). Adjuvant radiotherapy reduced seizures at recurrence in a univariate analysis (OR 0.14, 0.03-0.7, p = 0.020). Patients with seizure freedom after surgery and AT displayed longer progression-free survival (PFS) (65, 24.5-105, vs 48 months, 32-63.5, p = 0.037). This study analyzed seizure control in patients with IDH1/2-mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH-mutant lower-grade glioma.

Exploring brain network oscillations during seizures in drug-naïve patients with juvenile absence epilepsy.

We aimed to investigate the brain network activity during seizures in patients with untreated juvenile absence epilepsy. Thirty-six juvenile absence epilepsy (JAE) patients with a current high frequency of seizures (more than five seizures during a 2 h EEG examination) were included. Each participant underwent a 2 h video EEG examination. Five 10 s EEG epochs for inter-ictal, pre-ictal, and post-ictal, and five 5 s EEG epochs for ictal states were extracted. Five 10 s resting-state EEG epochs for each participant from a sex- and age-matched healthy control (HC) were enrolled. The topological parameters of the brain networks were calculated using a graph theory analysis. Compared with the resting state of the HC group, the global efficiency, local efficiency, and clustering coefficients of the JAE group decreased in the inter-ictal state. In addition, the ictal state showed significantly increased global and local efficiency and clustering coefficients (p < 0.05) and a decreased small-world index and the shortest path length (p < 0.05) in the theta and alpha bands, compared to the remaining states within the JAE group. Moreover, subgroup analysis revealed that those JAE patients with typical 3 Hz discharges had upgraded global efficiency, local efficiency, and clustering coefficients in both delta and beta1 bands, compared to those JAE patients with non-3 Hz discharges during seizures. The present study supported the idea that the changes in the EEG brain networks in JAE patients are characterized by decreased global and local efficiency and clustering coefficient in the alpha band. Moreover, the onset of seizures is accompanied by excessively enhanced network efficiency. JAE patients with different ictal discharge patterns may have different functional network oscillations.

A comprehensive systematic literature review of the burden of illness of Lennox-Gastaut syndrome on patients, caregivers, and society.

Fully elucidating the burden that Lennox-Gastaut syndrome (LGS) places on individuals with the disease and their caregivers is critical to improving outcomes and quality of life (QoL). This systematic literature review evaluated the global burden of illness of LGS, including clinical symptom burden, care requirements, QoL, comorbidities, caregiver burden, economic burden, and treatment burden (PROSPERO ID: CRD42022317413). MEDLINE, Embase, and the Cochrane Library were searched for articles that met predetermined criteria. After screening 1442 deduplicated articles and supplementary manual searches, 113 articles were included for review. A high clinical symptom burden of LGS was identified, with high seizure frequency and nonseizure symptoms (including developmental delay and intellectual disability) leading to low QoL and substantial care requirements for individuals with LGS, with the latter including daily function assistance for mobility, eating, and toileting. Multiple comorbidities were identified, with intellectual disorders having the highest prevalence. Although based on few studies, a high caregiver burden was also identified, which was associated with physical problems (including fatigue and sleep disturbances), social isolation, poor mental health, and financial difficulties. Most economic analyses focused on the high direct costs of LGS, which arose predominantly from medically treated seizure events, inpatient costs, and medication requirements. Pharmacoresistance was common, and many individuals required polytherapy and treatment changes over time. Few studies focused on the humanistic burden. Quality concerns were noted for sample representativeness, disease and outcome measures, and reporting clarity. In summary, a high burden of LGS on individuals, caregivers, and health care systems was identified, which may be alleviated by reducing the clinical symptom burden. These findings highlight the need for a greater understanding of and better definitions for the broad spectrum of LGS symptoms and development of treatments to alleviate nonseizure symptoms.

Neurophysiological Methods for Diagnostics and Treatment Monitoring in Patients of Advanced Age with Epilepsy

Through the last decades the duration of life and the number of elderly people is rapidly growing. In this age group morbidity of epilepsy is increasing very fast. Neurophysiological methods play an important role in diagnostics, classification of the disease and the type of the seizures, and in treatment monitoring in the elderly with epilepsy. The aim of the present study was to establish the significance of neurophysiological methods for diagnostics and treatment monitoring, as well as their relation with particular clinical characteristics of the disease in elderly patients. The study group consisted of 297 consecutive patients with epilepsy (average age 69.25±5.00 years). The methods used were documentary analysis, an interview of clinical factors, EEG (basic and control), video-EEG and statistical methods. Patients with longer duration of the disease were with significant worse neurophysiological results, higher seizure frequency and more in number antiepileptic medications. Epilepsy in the elderly is a major and growing issue. The results of the study will be useful in diagnostics and treatment monitoring in this age group.

Tuberous sclerosis complex in adulthood: focus on epilepsy prognosis

ObjectiveTypically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical features and severity of TSC in adults and on the prognosis of epilepsy are scarce. We analyzed the clinical and genetic features of a cohort of adult patients with TSC, to identify the prognostic predictors of seizure remission after a long follow-up. MethodWe conducted a retrospective analysis of patients diagnosed with TSC according to the updated international diagnostic criteria. Pearson’s chi-square or Fisher’s exact test and Mann Whitney U test were used to compare variables among the Remission (R) and Non-Remission (NR) group. Univariate and multivariate logistic regression analyses were performed. ResultsWe selected 43 patients with TSC and neurological involvement in terms of epilepsy and/or brain lesions, attending the Epilepsy Center of our Institute: of them, 16 (37.2%) were transitioning from the pediatric care and 6 (13.9%) were referred by other specialists. Multiorgan involvement includes cutaneous (86.0%), nephrological (70.7%), hepatic (40.0%), ocular (34.3%), pneumological (28.6%) and cardiac (26.3%) manifestations.Thirty-nine patients (90.7 %) had epilepsy. The mean age at seizure onset was 4 ± 7.3 years: most patients (29, 76.3 %) presented with focal seizures or spasms by age 3 years; only 2 (5.3 %) had seizure onset in adulthood. Twenty-seven patients (69.2 %) experienced multiple seizure types overtime, 23 (59.0 %) had intellectual disability (ID). At last assessment, 14 (35.9 %) were seizure free (R group) and 25 (64.1 %) had drug-resistant seizures (NR group). At logistic regression univariate analysis, ID (OR 7.9, 95 % CI 1.8––34.7), multiple seizure types lifelong (OR 13.2, 95 % CI 2.6– 67.2), spasms/tonic seizures at presentation (OR 6.5, 95 % CI 1.2––35.2), a higher seizure frequency at onset (OR 5.4, 95 % CI 1.2––24.3), abnormal neurological examination (OR 9.8, 95 % CI 1.1––90.6) and pathogenic variants in TSC2 (OR 5.4, 95 % CI 1.2––24.5) were significantly associated with non-remission. In the multivariate analysis, both ID and multiple seizure types lifelong were confirmed as independent predictors of poor seizure outcome. ConclusionsIn our cohort of adult patients with TSC, epilepsy remains one of the main neurological challenges with only 5.3% of cases manifesting in adulthood. Approximately 64% of these patients failed to achieve seizure remission. ID and multiple seizure types were the main predictors of poor outcome. Nephrological manifestations require continuous specific follow-up in adults.

Serum concentrations of complement C3 and C4 in dogs with idiopathic epilepsy.

High concentrations of complement factors are presented in serum of animal epilepsy models and human patients with epilepsy. To determine whether complement dysregulation occurs in dogs with idiopathic epilepsy (IE). The study included 49 dogs with IE subgrouped into treatment (n = 19), and nontreatment (n = 30), and 29 healthy dogs. In this case-control study, the serum concentrations of the third (C3) and fourth (C4) components of the complement system were measured using a canine-specific ELISA kit. Serum C3 and C4 concentrations were significantly higher in dogs with IE (C3, median; 4.901 [IQR; 3.915-6.673] mg/mL, P < .001; C4, 0.327 [0.134-0.557] mg/mL, P = .03) than in healthy control dogs (C3, 3.550 [3.075-4.191] mg/mL; C4, 0.267 [0.131-0.427] mg/mL). No significant differences were observed in serum C3 and C4 concentrations between dogs in the treatment (C3, median; 4.894 [IQR; 4.192-5.715] mg/mL; C4, 0.427 [0.143-0.586] mg/mL) and nontreatment groups (C3, 5.051 [3.702-7.132] mg/mL; C4, 0.258 [0.130-0.489] mg/mL). Dogs with a seizure frequency >3 times/month had significantly higher serum C3 (6.461 [4.695-8.735] mg/mL; P < .01) and C4 (0.451 [0.163-0.675] mg/mL; P = .01) concentrations than those with a seizure frequency ≤3 times/month (C3, 3.859 [3.464-5.142] mg/mL; C4, 0.161 [0.100-0.325] mg/mL). Dysregulation of classical complement pathway was identified in IE dogs. Serum C3 and C4 concentrations could be diagnostic biomarkers for IE in dogs with higher seizure frequency.

Risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes.

To explore risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes (BECT). This is a clinical comparative study. The subjects of study were 67 children with BECT from the Outpatient Department of Pediatric Neurology in Xingtai People's Hospital from January 2019 to January 2022. According to the occurrence of ESES, the enrolled children were divided into control group which included BECT children without ESES and the observation group which included BECT children with ESES. Compared differences of the two groups in the age of first seizure, the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and discharge side of electroencephalogram (EEG). There was no statistical difference between the two groups in the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and the distribution of EEG discharges in the left and right cerebral areas(P>0.05). Statistical differences were observed in the age of the first seizure, whether the seizures occurred after treatment, and EEG discharges in unilateral/bilateral cerebral areas (P<0.05). Furthermore, the collinearity test and Logistic regression analysis showed that the age of the first seizure, the frequency of seizures before treatment, and whether the seizures occurred after treatment were independent risk factors for the occurrence of ESES in BECT (P<0.05). Clinically, the occurrence of ESES in children with BECT may be related to the younger age of the first seizure, higher frequency of seizures before treatment, and the occurrence of seizures after treatment.

Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy

BackgroundThis study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE).MethodsA consecutive series of patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as ≤ 2 seizures/month and > 2 seizures/month, respectively. Systemic leukocyte gene expression was analyzed for prognostic value for TLE seizure frequency. All differentially expressed genes were analyzed, with Ingenuity® Pathway Analysis (IPA®) and Reactome, to identify leukocyte gene expression and biological pathways with prognostic value for seizure frequency.ResultsThere were ten males and six females with a mean age of 39.4 years (range: 16 to 62 years, standard error of mean: 3.6 years). There were five patients in the high and eleven patients in the low seizure frequency cohorts, respectively. Based on a threshold of twofold change (p < 0.001, FC > 2.0, FDR < 0.05) and expression within at least two pathways from both Reactome and Ingenuity® Pathway Analysis (IPA®), 13 differentially expressed leukocyte genes were identified which were all over-expressed in the low when compared to the high seizure frequency groups, including NCF2, HMOX1, RHOB, FCGR2A, PRKCD, RAC2, TLR1, CHP1, TNFRSF1A, IFNGR1, LYN, MYD88, and CASP1. Similar analysis identified four differentially expressed genes which were all over-expressed in the high when compared to the low seizure frequency groups, including AK1, F2R, GNB5, and TYMS.ConclusionsLow and high seizure frequency TLE are predicted by the respective upregulation and downregulation of specific leukocyte genes involved in canonical pathways of neuroinflammation, oxidative stress and lipid peroxidation, GABA (γ-aminobutyric acid) inhibition, and AMPA and NMDA receptor signaling. Furthermore, high seizure frequency-TLE is distinguished prognostically from low seizure frequency-TLE by differentially increased specific leukocyte gene expression involved in GABA inhibition and NMDA receptor signaling. High and low seizure frequency patients appear to represent two mechanistically different forms of temporal lobe epilepsy based on leukocyte gene expression.

Drug resistant epilepsy and associated factors among children with epilepsies in tanzania: a cross-sectional study

BackgroundEpilepsy contributes to high morbidity among children and adolescents in developing countries. A quarter of all children with epilepsy will be resistant to anti-seizure medications (ASMs), with associated neurocognitive impairments and risk of higher mortality. This study aimed to estimate and characterize drug-resistant epilepsy (DRE) (defined as failure to achieve sustained remission after adequate trials of two tolerated and appropriately chosen ASMs) and its associated factors among children and adolescents with epilepsies attending the pediatric neurology clinic at Muhimbili National Hospital (MNH), Dar es Salaam Tanzania.MethodsThis cross-sectional study was conducted from June 2020 to June 2021. Children with epilepsies and who had been treated with ASMs for at least 3 months were eligible for inclusion. Exclusion criteria included children whose caregivers denied consent and those who exhibited acute medical conditions necessitating admission on the scheduled visit day. Data on demographic characteristics, perinatal history, detailed history of the seizures semiology, drug history, magnetic resonance imaging (MRI), and electroencephalography (EEG) results were obtained from caregivers and medical records available during recruitment. Seizures and epilepsies were classified using the 2017 International League Against Epilepsy (ILAE) classification. Logistic regression was used to determine factors associated with DRE.ResultsA total of 236 children and adolescents aged between 4 months and 15 years (Median age 72 months (IQR = 42–78)) were enrolled in this study. We found the proportion of DRE to be 14.8% in this cohort. Of the thirty-five patients with DRE, 60% had generalized epilepsy and almost 25% had a diagnosis of an epilepsy syndrome, the most common being Lennox-Gastaut syndrome (LGS). Structural abnormalities on brain MRI were seen in almost 80% of all patients with DRE, the most prevalent being cystic encephalomalacia, which was observed in 34% of patients. Patients using both ASMs and alternative therapies accounted for 9% of this cohort. The onset of seizures during the first month of life (aOR = 1.99; 95%CI 1.7–4.6; p = 0.031) and high initial seizure frequency (aOR = 3.6; 95%CI 1.6-8;p = 0.002) were found to be independently associated with DRE.ConclusionThe proportion of DRE in Tanzania is high. Patients with neonatal onset seizures and high initial seizure frequency should be followed up closely to ensure early diagnosis of DRE.