Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings.

OBJECTIVE: The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics. METHODS: We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy. RESULTS: Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance. SIGNIFICANCE: JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.

Social outcome and psychiatric comorbidity of generalized epilepsies - A case-control study.

OBJECTIVE: To investigate social outcome and psychiatric comorbidity of patients with idiopathic/genetic generalized epilepsies (IGEs) and its subtypes (epilepsy with generalized tonic-clonic seizures alone [EGTCS], juvenile absence epilepsy [JAE], and juvenile myoclonic epilepsy [JME]). METHODS: A cohort of 402 adult patients with IGE from the Danish island Funen was matched with 4020 randomly selected geography-, age-, and sex-matched controls via the Danish Civil Registration System. Based on register data, we compared social status measured by cohabitant status, educational attainment, income, affiliation to labor market, and psychiatric comorbidity. RESULTS: As compared to controls, patients with IGE had similar cohabitant status but fewer children (no children: 59.0% vs 50.9%), and lower educational level (primary school only: 46.0% vs 37.3%), employment rate (outside of workforce: 56.7% vs 46.5%), and income (low income: 32.6% vs 24.9%) (P < 0.001 for all comparisons). Having IGE was associated with higher a proportion of psychiatric comorbidity (IGE, 22.6%; controls, 13.0%) (P < 0.001). Seizure-free patients did not differ from controls; patients with persistent seizures had lower incomes and employment rates. In the IGE subgroup analyses, JME was associated with worse social status in all parameters studied (eg, 65.9% of JME patients were outside the workforce vs 44.5% of matched controls; P < 0.001), whereas no adverse social status was identified in patients with EGTCS and JAE. SIGNIFICANCE: Patients with IGE in general and JME in particular have poorer social status and more psychiatric comorbidity than matched population controls without epilepsy. Poor seizure control was associated with social status and may contribute to negative socioeconomic consequences associated with IGE.

Calidad de vida en pacientes adultos con epilepsia generalizada idiopática. Estudio EPILAK / Quality of life in adult patients with idiopathic generalised epilepsy. The EPILAK study

INTRODUCCIÓN: La calidad de vida (CV) es un aspecto importante en el tratamiento de los pacientes con epilepsia. OBJETIVO: Analizar la CV mediante el Quality of Life in Epilepsy Inventory-10 (QOLIE-10) en adultos con epilepsia generalizada idiopática y estudiar factores asociados a una peor CV. Pacientes y método. Estudio transversal, multicéntrico, observacional, realizado por 141 neurólogos de todas las comunidades autónomas de España. Cada investigador analizaba el QOLIE-10 de dos varones y dos mujeres mayores de 18 años con epilepsia generalizada idiopática visitados de forma consecutiva en consulta pública o privada. Los resultados se estandarizaron: 0 era la peor CV y 100, la mejor. RESULTADOS: Se analizó a 546 pacientes. Mujeres: 51,1% (n = 279). Edad media: 36 ± 15,3 años (18-87). Ausencias infantiles: 7,5% (n = 41); ausencias juveniles: 9,2% (n = 50); mioclónica juvenil: 29,8% (n = 163); sólo crisis tonicoclónicas: 53,5% (n = 292). Monoterapia: 63,2% (n = 345). Libres de crisis en el último año: 53,1% (n = 290). Comorbilidad psiquiátrica: ansiedad: 28,4% (n = 155); depresión: 14,1% (n = 77); déficit de atención: 10,1% (n = 55). Condición laboral: trabajador/a en activo: 47,2% (n = 258); estudiante: 20% (n = 109); amo/a de casa: 7,3% (n = 40); pensionista: 10,2% (n = 56); en paro: 14,3% (n = 78). Estado civil: casado/a o en pareja: 49,1% (n = 268); soltero/a: 43,7% (n = 239). Puntuación media en el QOLIE-10: 71,4 ± 19,1. Sexo femenino (p = 0,006), mayor frecuencia de crisis (p < 0,001), politerapia (p < 0,001), comorbilidad psiquiátrica (p < 0,001) y desempleo (p < 0,001) se asociaron de forma significativa con una peor CV. CONCLUSIONES: La CV de los pacientes con epilepsia generalizada idiopática/genética está afectada por el mal control de las crisis, la comorbilidad psiquiátrica y el desempleo, y las mujeres presentan una mayor afectación que los hombres

INTRODUCTION. Quality of life (QoL) is an important aspect in the treatment of patients with epilepsy. AIM. To analyse the QoL using the Quality of Life in Epilepsy Inventory-10 (QOLIE-10) in adults with idiopathic generalised epilepsy and to study factors associated with a worse QoL. PATIENTS AND METHODS. A cross-sectional, multicentre, observational study conducted by 141 neurologists in all the autonomous communities of Spain. Each researcher analysed the QOLIE-10 of two males and two females over 18 years of age with idiopathic generalised epilepsy seen consecutively in public or private practice. The results were standardised: 0 was the worst QoL and 100 was the best. RESULTS. A total of 546 patients were analysed. Women: 51.1% (n = 279). Mean age: 36 ± 15.3 years old (18-87). Childhood absence seizures: 7.5% (n = 41); juvenile absence seizures: 9.2% (n = 50); juvenile myoclonic seizures: 29.8% (n = 163); only tonic-clonic seizures: 53.5% (n = 292). Monotherapy: 63.2% (n = 345). Seizure-free in the last year: 53.1% (n = 290). Psychiatric comorbidity: anxiety: 28.4% (n = 155); depression: 14.1% (n = 77); attention deficit: 10.1% (n = 55). Employment status: in active employment: 47.2% (n = 258); student: 20% (n = 109); housewife/husband: 7.3% (n = 40); pensioner: 10.2% (n = 56); unemployed: 14.3% (n = 78). Marital status: married or in a relationship: 49.1% (n = 268); single: 43.7% (n = 239). Mean score on the QOLIE-10: 71.4 ± 19.1. Being female (p = 0.006), greater frequency of seizures (p < 0.001), polytherapy (p < 0.001), psychiatric comorbidity (p < 0.001) and unemployment (p < 0.001) were significantly associated with a worse QoL. CONCLUSIONS. The QoL of patients with idiopathic/genetic generalised epilepsy is affected by poor seizure control, psychiatric comorbidity and unemployment, and women are more affected than men

Effect of add-on melatonin on seizure outcome, neuronal damage, oxidative stress, and quality of life in generalized epilepsy with generalized onset motor seizures in adults: A randomized controlled trial.

Epilepsy treatment is challenging because of multiple impediments like lack of efficacy of monotherapy, adverse drug reactions, and different comorbidities. Add-on therapy to first-line antiepileptics may be the option to overcome therapeutic hurdles. The present randomized, double-blind, add-on placebo-controlled clinical trial was conducted to evaluate the effect of add-on melatonin in the treatment of generalized epilepsy with generalized onset motor seizure in adults. The control group (n = 52) received add-on placebo, and the test group (n = 52) received add-on melatonin (3 mg/day) with valproate (20 mg/kg in two divided doses). Clinical evaluation of seizure frequency, Chalfont-National Hospital seizure severity scale (NHS3), Pittsburgh sleep quality index (PSQI), quality of life in epilepsy inventory, Epworth sleepiness scale (ESS), and biochemical estimation of serum neuron-specific enolase (NSE) and glutathione reductase were done at baseline and compared with follow-up at 8 weeks. Among 104 patients randomized [mean (SD) age of 27.6 (11.5); 84 (80.8%) male], 88 (84.6%) completed the trial. The responder rate and seizure-free rate in the test group were significantly (p = 0.006 and 0.034) higher than the control group. There was a significantly higher reduction in the frequency of seizures (p = 0.016) and NHS3 (-2.39; 95%CI: -4.56 to -0.21; p = 0.032) in the test group compared to the control group. Similarly, improvement in PSQI (-1.40; 95%CI: -2.64 to -0.15; p = 0.029) was significantly better in the test group. There was no significant difference in the change in ESS (p = 0.621) and quality of life scoring (p = 0.456) between the study groups. The decrease in serum NSE was significantly higher with the test group compared to the control group (-2.01; 95% CI: -3.74 to -0.27; p = 0.024). Add-on melatonin increased serum glutathione reductase significantly (p = 0.038), but there was no significant difference between the groups (p = 0.685). Add-on melatonin with valproate for generalized epilepsy with generalized onset motor seizures in adults can achieve a significantly better clinical outcome by reducing the seizure frequency, severity and attaining a better seizure-free rate in comparison to the control group.

Impaired empathy in patients with idiopathic generalized epilepsy: An event-related potentials study.

PURPOSE: Epilepsy is a common neurological disorder that may be complicated by neurobehavioral comorbidities. In a previous study, we identified impairment of empathy in patients with idiopathic generalized epilepsy (IGE). However, the temporal processing of empathy in patients with IGE is not well understood. METHODS: We investigated empathy for pain and self-reported empathy in 21 patients with IGE and 22 healthy control subjects. All study participants were required to complete a pain empathy task involving images of individuals in pain and neutral conditions during recording of event-related potentials. RESULTS: Compared with the controls, the patients with IGE showed impaired cognitive empathy but intact emotional empathy on the Chinese version of the Interpersonal Reactivity Index; they also had normal N1, N2, and late positive potential (LPP) but lower P3 amplitudes evoked by depictions of pain in others when compared with neutral images during the pain judgment task; the difference in the effects of pain empathy on the pain task between the IGE group and the control group was statistically significant. CONCLUSION: These results indicate that later processing of pain empathy is impaired but early processing is intact in patients with IGE. The present study extends the findings of our previous behavioral study by providing solid evidence of impaired empathy in patients with IGE at the neural processing level.

Characterizing Sunflower syndrome: a clinical series.

To characterize the clinical phenotype of Sunflower syndrome. Sunflower syndrome is a rare photosensitive epilepsy syndrome characterized by highly stereotyped seizures, photosensitivity, and heliotropism. We retrospectively reviewed the medical records of patients seen in the Massachusetts General Hospital for Children (MGHfC) pediatric epilepsy program with a history of Sunflower syndrome. Twenty-four patients were identified; 18 were female. At the time of initial MGHfC evaluation, patients' ages ranged from 6.4 to 25 years, with a median age of 11.5 years. All patients presented with hand-waving episodes (HWEs), although one patient no longer demonstrates this, but now has eye blinking episodes on exposure to light. Four have associated eye fluttering as a component of their most prevalent light-induced seizures. The average age at onset of HWEs was six years. Seventeen developed other symptoms prior to the onset of HWEs. The most prevalent symptom was an attraction to light and possible absence seizures. Light-induced seizures were generally refractory to broad-spectrum antiepileptic drugs (AEDs). Only three patients had a reduction of HWEs with the use of AEDs. Several non-pharmacological strategies reduced seizure frequency, however, efficacy varied. These non-pharmacological strategies included avoiding stimulus, focusing on other tasks, and occupying or restraining the hand that was involved in hand-waving. The use of tinted glasses reduced seizure frequency in 17 patients, however, no patient achieved seizure freedom. Twenty-two patients had available EEGs, 20 of which showed interictal epileptiform discharges. Additionally, many of the patients experienced a negative impact on their self-concept due to anxiety, depression, or negative interactions with peers. Sunflower syndrome is a generalized, pharmacoresistant epilepsy with childhood onset and remains poorly understood. To improve clinical care and scientific understanding, long-term prospective research exploring the natural history, etiology, and effective treatments for Sunflower syndrome should be conducted. [Published with video sequence].

Behavioral phenotypes of childhood idiopathic epilepsies.

OBJECTIVE: To characterize the presence and nature of discrete behavioral phenotypes and their correlates in a cohort of youth with new and recent onset focal and generalized epilepsies. METHODS: The parents of 290 youth (age = 8-18 years) with epilepsy (n = 183) and typically developing participants (n = 107) completed the Child Behavior Checklist for children aged 6-18 from the Achenbach System of Empirically Based Assessment. The eight behavior problem scales were subjected to hierarchical clustering analytics to identify behavioral subgroups. To characterize the external validity and co-occurring comorbidities of the identified subgroups, we examined demographic features (age, gender, handedness), cognition (language, perception, attention, executive function, speed), academic problems (present/absent), clinical epilepsy characteristics (epilepsy syndrome, medications), familial factors (parental intelligence quotient, education, employment), neuroimaging features (cortical thickness), parent-observed day-to-day executive function, and number of lifetime-to-date Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses. RESULTS: Hierarchical clustering identified three behavioral phenotypes, which included no behavioral complications (Cluster 1, 67% of epilepsy cohort [n = 122]), nonexternalizing problems (Cluster 2, 11% of cohort [n = 21]), and combined internalizing and externalizing problems (Cluster 3, 22% of cohort [n = 40]). These behavioral phenotypes were characterized by orderly differences in personal characteristics, neuropsychological status, history of academic problems, parental status, cortical thickness, daily executive function, and number of lifetime-to-date DSM-IV diagnoses. Cluster 1 was most similar to controls across most metrics, whereas Cluster 3 was the most abnormal compared to controls. Epilepsy syndrome was not a predictor of cluster membership. SIGNIFICANCE: Youth with new and recent onset epilepsy fall into three distinct behavioral phenotypes associated with a variety of co-occurring features and comorbidities. This approach identifies important phenotypes of behavior problem presentations and their accompanying factors that serve to advance clinical and theoretical understanding of the behavioral complications of children with epilepsy and the complex conditions with which they co-occur.

Pathways to quality of life in adolescents with genetic generalized epilepsy: The role of seizure features and affective symptoms.

Both clinical features of seizures and affective problems (i.e., depressive and/or anxious symptoms) affect quality of life perception in patients with epilepsy. Although genetic generalized epilepsies (GGEs) represent one-third of all epilepsies, very few studies focused on the association among seizures, affective problems, and perceived quality of life in pediatric patients with GGE. Here, we assessed the relative contributions of seizure characteristics and affective symptoms on quality of life in patients with adolescence-onset GGE. Forty pediatric outpatients completed self-report questionnaires on affective symptoms and quality of life. Sociodemographic and clinical variables were obtained from medical charts. Affective symptoms were present in 40% of patients. Higher scores emerged in patients who were seizure-free at the time of the survey for both the physical and mental components of quality of life. Higher seizure frequency was significantly associated with lower quality of life scores in the mental component, whereas the presence of depressive and/or anxious symptoms was significantly associated with lower scores in the physical component. These associations were confirmed after controlling for sociodemographic confounders. These findings suggest that adolescents with GGE are at increased risk for affective symptoms. Moreover, both GGE-related clinical features (i.e., seizure frequency) and the presence of affective symptoms (i.e., depression, anxiety) are relevant and independent contributors to quality of life. The investigation of affective problems is warranted to be included in routine assessments of GGE in pediatric populations.

Pleiotropy of polygenic factors associated with focal and generalized epilepsy in the general population.

Epilepsy is clinically heterogeneous, and neurological or psychiatric comorbidities are frequently observed in patients. It has not been tested whether common risk variants for generalized or focal epilepsy are enriched in people with other disorders or traits related to brain or cognitive function. Here, we perform two brain-focused phenome association studies of polygenic risk scores (PRS) for generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) with all binary brain or cognitive function-related traits available for 334,310 European-ancestry individuals of the UK Biobank. Higher GE-PRS were associated with not having a college or university degree (P = 3.00x10-4), five neuroticism-related personality traits (P<2.51x10-4), and having ever smoked (P = 1.27x10-6). Higher FE-PRS were associated with several measures of low educational attainment (P<4.87x10-5), one neuroticism-related personality trait (P = 2.33x10-4), having ever smoked (P = 1.71x10-4), and having experienced events of anxiety or depression (P = 2.83x10-4). GE- and FE-PRS had the same direction of effect for each of the associated traits. Genetic factors associated with GE or FE showed similar patterns of correlation with genetic factors associated with cortical morphology in a subset of the UKB with 16,612 individuals and T1 magnetic resonance imaging data. In summary, our results suggest that genetic factors associated with epilepsies may confer risk for other neurological and psychiatric disorders in a population sample not enriched for epilepsy.

Accelerated long-term forgetting is not evident in adults with genetic generalized epilepsy irrespective of the paradigm used.

Accelerated long-term forgetting (ALF) is a recently discovered memory disorder characterized by intact acquisition and retention over short delays, followed by abnormally fast rates of forgetting. Accelerated long-term forgetting has been repeatedly found in children, but not in adults, with genetic generalized epilepsy (GGE). It is possible that this discrepancy is due to a difference in paradigms used in these studies. The current study aimed to determine whether adults with GGE displayed ALF using two paradigms, one that required complete learning and another one that did not. In addition, we explored the relationships with everyday memory difficulties, working memory, mood, and epilepsy variables. Fourteen adults with GGE were compared with 16 healthy controls on two verbal memory tests: a modified version of the California Verbal Learning Test learned to a criterion of 100% (complete learning) and Logical Memory from the Wechsler Memory Scale (Fourth Edition) presented only once (incomplete learning). Recall was tested at 2 min, 30 min, and 1 week, and recognition at 1 week only. Working memory, everyday memory, and mood were also assessed. We found no evidence of ALF on either of the two verbal memory paradigms on recall or recognition tests although patients displayed significantly poorer working memory. Moreover, patients with GGE reported significantly more memory difficulties in everyday life, and these were associated with greater mood disturbances but not with memory tests scores. Greater number of antiepileptic drugs and epilepsy severity also related to memory scores on some tests. Our study suggests that a difference in paradigms used to investigate ALF in children and adults with GGE is unlikely to explain the differences in findings. The study tentatively raises a hypothesis that developmental factors may play a role in ALF in patients with GGE; children with GGE may grow out of ALF. Nevertheless, this hypothesis would need to be tested in a longitudinal study that would follow patients from childhood to early adulthood.

Social impairment and stigma in genetic generalized epilepsies.

INTRODUCTION: Patients with epilepsy have poor social outcome. Multifactorial factors are usually involved, but among them, stigma features may have an important role. Genetic generalized epilepsies (GGEs) were previously considered "benign" syndromes. The aim of our study was to assess social impairment and stigma in GGE and to evaluate differences between the following GGE subsyndromes: juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and generalized tonic-clonic seizures alone (GTCSA). Additionally, we compared these outcomes with outcomes from a cohort of patients with epilepsy with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), a severe and difficult-to-treat syndrome. Results were compared with social data from the general population. METHODS: Adult patients with epilepsy with a previously classified GGE or MTLE-HS were consecutively invited to fill in a sociodemographic and stigma questionnaire in outpatient clinic. Clinical data and psychiatric comorbidities were retrieved from clinical notes. RESULTS: Questionnaires from 333 patients were obtained: 226/67% from patients with GGE (JME: 106/31.8%, GTCSA: 74/22.2%, and JAE: 46/13.8%) and 107/32.1% from patients with MTLE-HS. We found that patients with GGE have a good academic achievement but they have increased difficulties in finding a partner, higher rates of divorce, and a reduced number of children per woman and per man when compared with general population. We also observed that patients with GGE have higher rates of unemployment (22.6%) and lower monthly income than general population. Severe problems in housing were only seen in GGEs. Of these, 3 patients (1.3%) were in homeless condition. Over half (52%) of patients with MTLE-HS and over a quarter (28%) of patients with GGE experienced felt stigma. Psychiatric comorbidity was highly prevalent among GGE (34.1%), especially in patients with refractory epilepsy. Mood and anxiety disorders were the most prevalent conditions. No other significant differences were found between GGE subsyndromes. DISCUSSION: We found an impairment in every social domain assessed (except in level of education) when compared with general population. Most of the social outcome parameters were unexpectedly close or similar to MTLE-HS or even worse as it was the prevalence of homelessness among GGE. Social impairment is underdiagnosed and might be considered in clinical practice even in syndromes for some time considered benign such as GGE.

Praxis induction and its relationship with cognition in genetic generalized epilepsy.

INTRODUCTION: Praxis induction (PI) is a reflex trait defined as the precipitation of epileptic discharges (ED) or seizures by cognition-guided tasks that often involve visuomotor coordination and decision-making. This is a characteristic of genetic generalized epilepsy (GGE), and especially of juvenile myoclonic epilepsy (JME). Additionally, several studies have described dysexecutive traits in these patients. Our objective was to analyze PI in the different syndromes of GGE and explore the relationship between PI and cognitive performance. METHODS: Sixty-one adult patients with GGE underwent video-electroencephalograph (EEG) during which a neuropsychological activation protocol (NPAP) was performed: reading, writing, calculations, crosswords, and tangram. Praxis induction was defined by the presence of ED during the NPAP with a persistence of at least twice seen on the basal EEG. All patients also underwent a comprehensive cognitive evaluation. RESULTS: We observed PI in 22 out of 61 patients (36%). Grouped by syndrome, PI was more frequent in adult patients with persistent childhood or juvenile absence epilepsy (JAE, 60%), followed by JME (42.1%) and in a lesser grade in patients with only tonic-clonic generalized seizures (9%). Patients classified as having PI did not obtain worse results in the cognitive evaluation. The presence of ED during the performance of a test was associated with a trend to lower results in that specific test. SIGNIFICANCE: Our study showed a relevant presence of PI in patients whose absence epilepsy persists into adulthood, and not only in JME, the syndrome classically associated with PI. According to our results, PI as a reflex trait does not imply necessarily a poorer cognitive phenotype, but the induction of frequent ED during the tasks could be associated with transient cognitive impairment.

Attention and inhibitory control deficits in patients with genetic generalized epilepsy and psychogenic nonepileptic seizure.

This study aimed to evaluate the attention and inhibitory control functions in patients with genetic generalized epilepsy (GGE) and psychogenic nonepileptic seizure (PNES) and compare the results with the healthy control subjects. A total of 30 patients with GGE, 30 patients with PNES, and 32 healthy control subjects were included in the study. The severity of attention and inhibitory control deficit, general intelligence status, and psychopathology screening in all subjects were respectively investigated with the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), the Wechsler Adult Intelligence Scale (WAIS), and the Symptoms Checklist 90-revised (SCL-90-R). Patients with PNES had severe impairments in all performed tasks compared with the control group and the group with GGE (p < 0.01), whereas patients with GGE had significantly lower attention quotient versus healthy subjects (p < 0.01). The full-scale attention quotient (FSAQ) and full-scale response control quotient (FSRCQ) in patients with PNES were significantly lower in comparison with GGE (47.83 ±â€¯32.68, 60.18 ±â€¯35.35, p < 0.01), respectively. Multiple regression analysis did not demonstrate any significant effect of seizure frequency or epilepsy duration on attention and inhibitory control deficits, but patient's intelligence quotient (IQ) showed a significant effect on FSAQ and FSRCQ (ß: 0.997, p < 0.001; ß: 0.933, p < 0.001, respectively). Attention and inhibitory control are significantly impaired in patients with GGE and PNES. The cognitive deficits in patients with GGE and PNES have potentially important clinical implications in planning their neuropsychological rehabilitation.

A transcranial sonography study of brainstem and its association with depression in idiopathic generalized epilepsy with tonic-clonic seizures.

Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with depression. But, up to date, the association of BR alterations in TCS with depression in patients with epilepsy has never been reported. This study was to investigate the possible role of BR examination via TCS in patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-TCS) and depression. Forty-six patients with IGE-TCS and 45 healthy controls were recruited. Echogenicity of the caudate nuclei (CN), lentiform nuclei (LN), substantia nigra (SN), and BR and widths of the lateral ventricle (LV) frontal horns and the third ventricle (TV) were assessed via TCS. The determination of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), and depression severity measured by Chinese version Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) and Beck Depression Inventory-II (BDI-II). The width of TV in patients with epilepsy was found significantly larger than that in healthy controls (p = 0.001), but there was no significant difference in TV width between patients with IGE-TCS with and without depression. There were no significant differences between patients with IGE-TCS and healthy controls in LV frontal horn width, as well as in SN, CN, LN, and BR echogenicity. Here, it seems that patients with IGE-TCS were detected with smaller SN echogenic area compared with controls though they had no statistical significance. Patients with IGE-TCS with hypoechogenic BR had significantly higher C-NDDI-E and BDI-II scores than those with normal BR signal, and most patients with IGE-TCS with depression exhibited hypoechogenic BR, but few patients with IGE-TCS without depression exhibited hypoechogenic BR. In conclusion, BR echogenic signal alterations in TCS can be a biomarker for depression in epilepsy, but it might not be associated with epilepsy itself. The alterations of SN echogenic area and TV width in TCS may reflect a potential role of SN and diencephalon structure in the pathogenesis of epilepsy, which needs to be further elucidated.

Efficacy, retention, and safety of brivaracetam in adult patients with genetic generalized epilepsy.

OBJECTIVE: The aim of this study was to evaluate the efficacy, tolerability, and retention of brivaracetam (BRV) in genetic generalized epilepsy (GGE) in real-life practice. METHODS: This is a retrospective cohort study of adult patients with GGE in whom BRV was started between 2016 and 2018, completing a follow-up period of ≥6 months. Clinical and electroencephalogram (EEG) characteristics were analyzed at baseline and at follow-up as outcome measures. RESULTS: Brivaracetam was started in 37 patients (mean age: 29.9 ±â€¯12.3 years; 73% women). Juvenile myoclonic epilepsy was the most common syndrome (43.2%). The primary indications for starting BRV were lack of efficacy (51.4%) and adverse events (AEs) (27%) of other antiepileptic drugs (AEDs). In total, 32.4% of patients received BRV monotherapy. Retention rate at 6 months was 81.1%; 83.8% of patients were considered responders, and 62.2% achieved seizure freedom. The primary reasons for withdrawal were treatment-emergent adverse events (TEAEs, 57.1%) and lack of efficacy (42.9%). The higher number of prior AED use was a risk factor for a lack of response [median = 4 (interquartile range (IQR): 3-4) vs 2 (IQR: 1-3); p < 0.05]. Patients with a previous response to valproic acid tended to have a higher response rate to BRV (86.7% vs 50%, p = 0.169). Eighty-three point eight percent (83.8%) of previous levetiracetam (LEV) responders also showed a good response to BRV. In terms of patients who presented LEV-related AEs, AE resolution was observed in 79.8%, particularly with regard to psychiatric AEs. Follow-up EEGs were compared with baseline EEGs in 25 patients (67.6%) during follow-up. Most patients showed a reduction (52%) or no change (36%) in interictal epileptiform discharge (IED) frequency. SIGNIFICANCE: Brivaracetam shows good responder and retention rates in GGE and is generally well tolerated. It is an appropriate alternative treatment for GGE, especially in refractory epilepsy and when other AEDs are not tolerated.

Facial emotion perception and social competence in children (8 to 16 years old) with genetic generalized epilepsy and temporal lobe epilepsy.

Facial emotion perception (FEP) impairments are common in adults with epilepsy and associated with impaired psychosocial functioning. Research into the presence of FEP deficits in children with epilepsy and the functional implications of these deficits is limited. The primary aims of this study were to assess FEP abilities in children (8 to 16 years old) with genetic generalized epilepsy (GGE) and temporal lobe epilepsy (TLE) and examine whether FEP is related to everyday social functioning. Forty-four children (8 to 16 years) with epilepsy (22 GGE, 22 TLE) and 22 typically developing controls completed the Pictures of Facial Affect (POFA) battery to assess FEP and a brief test of intellectual functioning (intelligence quotient [IQ]). Parents completed questionnaires assessing social competence of their child. Neurologists completed the Global Assessment of Severity of Epilepsy (GASE) scale as a measure of overall epilepsy severity. Demographic and clinical information was obtained from medical records and clinical interviews with parents. Findings revealed significant, overall FEP impairments and reduced social competence in children with GGE and TLE compared to controls. The magnitude of FEP impairment (i.e., across all emotions) was comparable in the two epilepsy groups, yet different emotions were impaired in each group: children with GGE were impaired in recognizing anger and disgust, whereas children with TLE were impaired in sadness and disgust, compared to controls. Contrary to expectations, total FEP accuracy was not significantly correlated with social competence in either epilepsy group. In conclusion, children with GGE and TLE have significant impairments recognizing emotional expressions on faces. Further research is needed to examine whether underlying FEP impairments relate to social and emotional functioning in children with epilepsy.

Social cognition in idiopathic generalized epilepsies and potential neuroanatomical correlates.

Social cognition allows us to elaborate mental representations of social relationships and use them appropriately in a social environment. One of its main attributes is the so-called Theory of Mind (ToM), which consists of the ability to attribute beliefs, intentions, emotions, and feelings to self and others. Investigating social cognition may help understand the poor social outcome often experienced by persons with Idiopathic Generalized Epilepsies (IGE), who otherwise present with normal intelligence. In recent years, several studies have addressed social cognition in subjects with focal epilepsies, while literature on social cognition in IGE is scarce, and findings are often conflicting. Some studies on samples of patients with mixed IGE showed difficulties in emotion attribution tasks, which were not replicated in a homogeneous population of patients with Juvenile Myoclonic Epilepsy alone. Impairment of higher order social skills, such as those assessed by Strange Stories Test and Faux Pas Tasks, were consistently found by different studies on mixed IGE, suggesting that this may be a more distinctive IGE-associated trait, irrespective of the specific syndrome subtype. Though an interplay between social cognition and executive functions (EF) was suggested by several authors, and their simultaneous impairment was shown in several epilepsy syndromes including IGE, no formal correlations among the two domains were identified in most studies. People with IGE exhibit subtle brain structural alterations in areas potentially involved in sociocognitive functional networks, including mesial prefrontal and temporoparietal cortices, which may relate to impairment in social cognition. Heterogeneity in patient samples, mostly consisting of groups with mixed IGE, and lack of analyses in specific IGE subsyndromes, represent evident limitations of the current literature. Larger studies, focusing on specific subsyndromes and implementing standardized test batteries, will improve our understanding of sociocognitive processing in IGE. Concomitant high-resolution structural and functional neuroimaging may aid the identification of its neural correlates. This article is part of the Special Issue "Epilepsy and social cognition across the lifespan".

Anxiety and depression symptoms disrupt resting state connectivity in patients with genetic generalized epilepsies.

OBJECTIVE: To analyze the lifetime trajectories in genetic generalized epilepsies (GGEs) and investigate the impact of symptoms of anxiety and depression on resting state functional connectivity (FC). METHODS: Seventy-four GGE patients were classified according to the pharmacological response as seizure-free (12 patients), pharmacoresistant (PhR; 14 patients), and fluctuating (FL; 48 patients). Fifty-four subjects completed both the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), and 38 also underwent 3-T resting state functional magnetic resonance imaging. These 38 patients were subdivided into a positive group (13 patients with concurrent symptoms of depression and anxiety) and a negative group (21 asymptomatic patients and four with mild anxiety or depression symptoms). For FC analysis of resting state networks, we matched 38 healthy asymptomatic volunteers and used the UF2C toolbox running on MATLAB2017/SPM12. RESULTS: The PhR group presented shorter duration of epilepsy (P = 0.016) and follow-up (P < 0.001) compared to the FL group. The PhR group showed higher levels (median = 20) on the BAI and BDI. Myoclonic seizures were the most difficult to control, as 50% of subjects persisted with them at last appointment, compared to generalized tonic-clonic seizures and absence seizures (<40%). Patients with concurrent anxiety and depression symptoms were 7.7 times more likely to exhibit pharmacoresistant seizures, although an increase of 1 year of epilepsy duration was associated with a decrease in the odds of presenting pharmacoresistance by a factor of 0.9. Overall, FC was altered between default mode network (DMN) and visuospatial/dorsal attention. However, only the positive group displayed abnormal FC between DMN and left executive control network, and between salience and visuospatial/dorsal attention. SIGNIFICANCE: Our findings may help clinicians to have a better understanding of GGE clinical course and increase attention to the potential relationship of psychopathologies and brain connectivity.

Language function in childhood idiopathic epilepsy syndromes.

PURPOSE: To examine the impact of diverse syndromes of focal and generalized epilepsy on language function in children with new and recent onset epilepsy. Of special interest was the degree of shared language abnormality across epilepsy syndromes and the unique effects associated with specific epilepsy syndromes. METHODS: Participants were 136 youth with new or recent-onset (diagnosis within past 12 months) epilepsy and 107 healthy first-degree cousin controls. The participants with epilepsy included 20 with Temporal Lobe Epilepsy (TLE; M age = 12.99  years, SD = 3.11), 41 with Benign Epilepsy with Centrotemporal Spikes (BECTS; M age = 10.32, SD = 1.67), 42 with Juvenile Myoclonic Epilepsy (JME; M age = 14.85, SD = 2.75) and 33 with absence epilepsy (M age = 10.55, SD = 2.76). All children were administered a comprehensive test battery which included multiple measures of language and language-dependent abilities (i.e., verbal intelligence, vocabulary, verbal reasoning, object naming, reception word recognition, word reading, spelling, lexical and semantic fluency, verbal list learning and delayed verbal memory). Test scores were adjusted for age and gender and analyzed via MANCOVA. RESULTS: Language abnormalities were found in all epilepsy patient groups. The most broadly affected children were those with TLE and absence epilepsy, whose performance differed significantly from controls on 8 of 11 and 9 of 11 tests respectively. Although children with JME and BECTS were less affected, significant differences from controls were found on 4 of 11 tests each. While each group had a unique profile of language deficits, commonalities were apparent across both idiopathic generalized and localization-related diagnostic categories. DISCUSSION: The localization related and generalized idiopathic childhood epilepsies examined here were associated with impact on diverse language abilities early in the course of the disorder.

Cortical excitability affects mood state in patients with idiopathic generalized epilepsies (IGEs).

Previously, we demonstrated an association between cortical hyperexcitability and mood disturbance in healthy adults. Studies have documented hyperexcitability in patients with idiopathic generalized epilepsies (IGEs; long-interval intracortical inhibition [LICI]) and high prevalence of mood comorbidities. This study aimed to investigate the influences of cortical excitability and seizure control on mood state in patients with IGEs. Single and paired-pulse transcranial magnetic stimulation (TMS) was applied to 30 patients with IGEs (16 controlled IGEs [cIGEs], 14 with treatment-resistant IGEs [trIGEs]), and 22 healthy controls (HCs) to assess cortical excitability with LICI. The Profile of Mood Sates (POMS) questionnaire was used to assess total mood disturbance (TMD), as well as, six mood domains: Depression, Confusion, Anger, Anxiety, Fatigue, and Vigor. To assess the effects of seizure control (HC vs. cIGEs vs. trIGEs) and LICI response (inhibitory vs. excitatory) on TMD, a two-way multivariate analysis of variance (MANOVA) was performed. Analyses revealed a significant main effect of long-interval intracortical inhibition (LICI) response on TMD (F(1, 46) = 4.69, p = 0.04), but not seizure control (F(2, 46) = 0.288, p = 0.75). Excitatory responders endorsed significantly higher TMD scores, indicating greater mood disturbance, than inhibitory responders (MD = -2.12; T (50) = -2.47, p = 0.04). Also, excitatory responders endorsed more items than inhibitory responders on the Depression (MD = -2.12; T (50) = -2.47, p = 0.04) and Fatigue (MD = -3.42; T (50) = -2.96, p = 0.03) subscales of the POMS. These findings provide further evidence of a relationship between hyperexcitability and mood disturbance, and indicate that cortical excitability may have greater influence on mood state than seizure control in patients with IGEs. Results also support theories for the underlying role of gamma-aminobutyric acid (GABA) network dysfunction in the etiology of depression. To better understand the clinical relevance and causal nature of these relationships, further investigation is warranted.