Structural insights of novel mutational frames in Bromodomain Containing-2 gene (BRD2) in juvenile myoclonic epilepsy: bed, bench, and laptop profiles.

PURPOSE: Juvenile myoclonic epilepsy (JME) is an adolescent onset type of idiopathic generalized epilepsies. Bromodomain containing protein-2 gene (BRD2), a transcriptional regulatory protein, has a susceptible role in the expression of JME. Considering the polymorphic variations observed in exon 3 of the BRD2 gene, we evaluated the molecular interactions with anti-seizure medication in individuals diagnosed with JME. METHODS: The genomic DNA was extracted from 5 mL of peripheral venous blood of JME participants (n = 55) and healthy control subjects (n = 55). Detailed anti-seizure medication and outcomes were noted during the study period. Identified novel mutations at nucleotide and protein sequences, compared by multiple sequence alignment. Wild-type (WT) and mutated-type (MT) structures were investigated for molecular docking and interactions with anti-seizure drugs. RESULTS: A common variant at c.1707G>A was found among 23 participants, while a single variant at c.1663ins C was found in one participant. The deletion positions were observed at c.1890delA, c.1892A>T, c.1895A>T, c.1896G>T, c.1897T>C, c.1898T>C, c.1899C>T, c.1900G>T, c.1901C>T and c.1902A>T exhibiting stop codon after p.111Pro>stop; these variants resulted in a truncated protein. In silico analysis was conducted to validate changes; docking analysis showed that novel variant has a significant role in the interactions with anti-seizure drugs. SIGNIFICANCE: Besides clinical and genetic outcomes, ∼5.45% unique genetical variations were observed in the participants. Significant mimicked at the binding site position (92-111) of human BRD2 ranges ∼8.2%, ∼16.4%, and ∼10.6%. Further, research is needed to identify the importance of polymorphism alterations at the binding site and their molecular interactions with anti-seizure drugs, which might be confirmed in a diverse population with JME.

Prevalence, nature, and severity of the psychiatric comorbidities and their impact on quality of life in adolescents with Juvenile myoclonic epilepsy.

INTRODUCTION: Adults with Juvenile myoclonic epilepsy (JME) are at increased risk for psychiatric comorbidities, personality traits, and abnormality in executive function. But studies on adolescents and their impact on quality of life are scarce in the literature. MATERIALS AND METHODS: This cross-sectional study was performed between August 2019 and October 2022 to compare the prevalence of psychiatric comorbidities in adolescents with JME and age and gender-matched healthy controls. After completing DSM-5 Structured Clinical Interview (SCID-5) initially in all patients, we measured the severity of individual psychiatric problems like anxiety, depression, and somatic symptoms by using an appropriate psychometric scale. We also measured both groups' intelligence quotient (IQ), executive function, and quality of life. RESULTS: One hundred patients with JME (14.3 ± 2.5 years, 48 boys) and 100 controls were enrolled. Psychiatric disorders were observed in 46% of JME and 6% of controls (p < 0.01). Psychiatric comorbidities noted in the patients with JME were: somatic symptom and related disorders(n = 14), anxiety (n = 13), adjustment disorders (n = 12), depression (n = 11), oppositional defiant disorder (n = 6), conduct disorder (n = 5), anorexia nervosa (n = 3), narcissistic (n = 3), histrionic (n = 1), substance-related disorder (n = 1), borderline (n = 2) and antisocial personality disorder (n = 2). The prevalence of depressive disorders, anxiety disorders, adjustment disorders, somatic symptoms, related disorders, and any personality disorder was significantly more in the JME group (p < 0.01 for all). Female gender, higher Epilepsy Stigma Scale score, and lower Epilepsy Outcome Expectancy Scale were significantly associated with depressive disorders (p = 0.04, 0.03, 0.03 respectively). Similarly, for anxiety, only female gender and lower Epilepsy Outcome Expectancy Scale were significant associated factors (p = 0.03, 0.02 respectively). CONCLUSIONS: Psychiatric disorders like anxiety, depression, and personality disorders are more frequent in adolescents with JME than in controls.

Electroencephalographic findings in asymptomatic relatives of patients with juvenile myoclonic epilepsy: relationship with the degree of kinship.

INTRODUCTION: A prevalence of 1 to 71% of electroencephalogram (EEG) abnormalities has been reported in asymptomatic relatives of patients with juvenile myoclonic epilepsy (JME). OBJECTIVE: To determine the frequency of EEG abnormalities in asymptomatic relatives of patients with JME according to the degree of kinship. METHODS: Prospective, analytical study. First-, second, and third-degree relatives of patients with JME who agreed to participate and signed informed consent were included. The analysis was descriptive, bivariate. RESULTS: 209 asymptomatic relatives were included, out of which 115 (55%) were females and 94 (45%) were males, with a mean age of 35.9 ± 16.9 (range between 6 and 73 years). Forty-four (21.1%) relatives had abnormal EEGs. First-degree relatives (12%) had abnormalities more frequently in comparison with second- and third-degree relatives (p = 0.007). CONCLUSIONS: EEG abnormalities were observed in one third of asymptomatic relatives. It is important to highlight that there were more alterations among first-degree relatives. In the future, these findings might enable for the risk of clinically developing the disease to be estimated and for genetic counseling to be provided.

INTRODUCCIÓN: Se ha reportado de 1 a 71 % de prevalencia de anormalidades en el electroencefalograma (EEG) de familiares asintomáticos de pacientes con epilepsia mioclónica juvenil (EMJ). OBJETIVO: Determinar la frecuencia de anormalidades en el EEG en familiares asintomáticos de pacientes con EMJ de acuerdo con el grado de parentesco. MÉTODOS: Estudio prospectivo y analítico. Se incluyeron familiares de primer, segundo y tercer grado de pacientes con EMJ, quienes aceptaron participar y firmaron el consentimiento informado. El análisis fue descriptivo bivariado. RESULTADOS: Se incluyeron 209 familiares asintomáticos, 115 (55 %) mujeres y 94 (45 %) hombres, con edad media de 35.9 ± 16.9 (rango entre seis y 73 años); 44 familiares (21.1 %) tuvieron EEG anormal. Los familiares de primer grado (12 %) cursaron con mayor frecuencia con anormalidades en comparación con los de segundo y tercer grado (p = 0.007). CONCLUSIONES: Se observaron anormalidades en el EEG de una tercera parte de los familiares asintomáticos. Es importante resaltar que existieron más alteraciones entre los familiares de primer grado. En un futuro, estos hallazgos permitirán estimar el riesgo de desarrollar la enfermedad clínicamente y brindar consejo genético.

The association between temperament features and childhood traumas in patients with juvenile myoclonic epilepsy

Background/aim: Epilepsy is a common chronic neurological problem that impairs daily activities, functionality, and quality of life. Childhood traumas (CTs) are known to be critical factors in the onset or development of many psychiatric and medical disorders. They also play a critical role in the development of temperament and personality. This study aimed to investigate the association between CTs and common temperament patterns and features seen in epilepsy patients. Materials and methods: The study included 38 patients who were diagnosed with juvenile myoclonic epilepsy (JME) and volunteered to participate in the study. In addition to the sociodemographic form and questions on disease features, Structured Clinical Interview for DSM-IV Axis I Disorders, Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire (TEMPS-A), Childhood Trauma Questionnaire (CTQ), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were administered to all participants. In the present study, a cut-off value of 35 was used for the CTQ scale. The patients with CTQ scores lower than 35 (50%, n = 19, Group 1) and the patients with CTQ scores above 35 (50%, n = 19, Group 2) were compared. Results: The comparison of TEMPS-A and its subscale scores in the JME patients in the groups with CTQ scores above or below a cut-off value detected significant differences between the groups in depressive and irritable temperament scores. The mean BDI scores were also different between the two groups. Furthermore, a significant positive correlation was detected between the disease duration, anxiety, and depression scores in the JME patients. A significant relationship was detected between the emotional neglect subscale score of the JME patients and the BDI scores. A significant positive correlation was found between the total disease duration, BDI, and BAI. Significant moderate-level relationships were found between the BDI score and irritable, depressive, cyclothymic, and anxious temperaments and between the BAI score and irritable, depressive, cyclothymic, and anxious temperaments. Conclusion: Several temperamental features of JME patients are related to CTs. More depressive symptoms are seen in JME patients with higher disease durations.

No evidence for a BRD2 promoter hypermethylation in blood leukocytes of Europeans with juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain-containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives. In contrast, we found a uniform low average percentage of methylation (<4.5%) for 13 CpG76-CpGs in whole blood cells from 782 unrelated European Caucasians, including 116 JME patients, 196 patients with genetic absence epilepsies, and 470 control subjects. We also failed to confirm an allelic association of the BRD2 promoter single nucleotide polymorphism (SNP) rs3918149 with JME (Armitage trend test, P = 0.98), and we did not detect a substantial impact of SNP rs3918149 on CpG76 methylation in either 116 JME patients (methylation quantitative trait loci [meQTL], P = 0.29) or 470 German control subjects (meQTL, P = 0.55). Our results do not support the previous observation that a high DNA methylation level of the BRD2 promoter CpG76 island is a prevalent epigenetic motif associated with JME in Caucasians.

Refractory juvenile myoclonic epilepsy: a meta-analysis of prevalence and risk factors.

BACKGROUND AND PURPOSE: Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome for which treatment response is generally assumed to be good. We aimed to determine the prevalence and prognostic risk factors for refractoriness of JME. METHODS: We systematically searched PubMed and EMBASE and included 43 eligible studies, reporting seizure outcome after antiepileptic drug (AED) treatment in JME cohorts. We defined refractory JME as persistence of any seizure despite AED treatment and performed a random-effects meta-analysis to assess the prevalence of refractory JME and of seizure recurrence after AED withdrawal in individuals with well-controlled seizures. Studies reporting potential prognostic risk factors in relation to seizure outcome were included for subsequent meta-analysis of risk factors for refractoriness. RESULTS: Overall, 35% (95% confidence interval, 29-41%) of individuals (n = 3311) were refractory. There was marked heterogeneity between studies. Seizures recurred in 78% (95% confidence interval, 52-94%) of individuals who attempted to withdraw from treatment after a period of seizure freedom (n = 246). Seizure outcome by publication year suggested that prognosis did not improve over time. Meta-analysis suggested six variables as prognostic factors for refractoriness, i.e. having three seizure types, absence seizures, psychiatric comorbidities, earlier age at seizure onset, history of childhood absence epilepsy and praxis-induced seizures. CONCLUSION: One-third of people with JME were refractory, which is a higher prevalence than expected. Risk factors were identified and can be used to guide treatment and counselling of people with JME.

Treatment and challenges with antiepileptic drugs in patients with juvenile myoclonic epilepsy.

BACKGROUND: Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges. METHOD: A questionnaire about the use of AEDs, adherence to therapy, and quality of life was given to patients with JME recruited from Drammen Hospital. Data regarding AEDs were confirmed from medical records at Drammen Hospital, Norway (2007-2018). Additional clinical interviews were performed, and a mixed method approach was applied. RESULTS: Ninety patients with defined JME diagnosis, 54/36 women/men aged 14-39 (mean: 25) years, were included. Only 29 (33%) were seizure-free. Within the last year, 21% experienced generalized tonic-clonic seizures (GTCS), and 68% had myoclonic jerks. Seventy-six (84%) used AEDs, 78% in monotherapy. A total of 10 AEDs were used;: most commonly valproate (n = 33), lamotrigine (n = 27), and levetiracetam (n = 21). Two-thirds of valproate users were men while all other AEDs were used more in females than in men. Valproate and levetiracetam displayed better efficacy against GTCS than lamotrigine. One-third often/sometimes forgot their medication nonintentionally while 14% had intentional poor adherence. The majority reported good quality of life (76%). No significant correlations between the use of AEDs, use of valproate, poor adherence, quality of life score, and seizure freedom were demonstrated. Half of the patients had serum concentrations measured every year, and two-thirds thought this was important. Qualitative interviews elucidated treatment challenges in JME;, adverse effect burden, adherence, and activities of daily life. CONCLUSION: Despite the use of AEDs in the majority of patients, only one-third were seizure-free. Other challenges included polypharmacy, the use of valproate in women, and variable adherence. This points to a need for closer follow-up in patients with JME.

Prevalence and clinical characteristics of headache in juvenile myoclonic epilepsy: experience from a tertiary epilepsy center.

The comorbidity of headache and epilepsy is often seen in neurological practice. The objective of this study was to assess the prevalence, types of, and risk factors for headache in juvenile myoclonic epilepsy (JME). We assessed a total of 200 patients and 100 healthy controls in our study. Headache was classified in participants using a self-administered questionnaire. Demographical, clinical features and headache characteristics were recorded. Seizure and headache temporal profiles were noted. Headache was present in 111 (56%) patients and 50 (50%) healthy participants. From these patients, 47 (42.3%) JME patients had migraine [30 (27%) migraine without aura (MO), 17 (15.3%) migraine with aura (MA)], 52 (46.8%) had tension type headache (TTH), 4 (3.6%) had both migraine and TTH, and 8 (7.2%) had other non-primary headaches. In the healthy control group, migraine was detected in 16 (32%) subjects, TTH in 33 (66%), both migraine and TTH in 1 (2%) subject. A positive migraine family history and symptom relief with sleep were more frequent in JME patients (p = 0.01). Headache was classified as inter-ictal in 82 (79.6%) patients and peri-ictal in 21 (20.4%) patients. In conclusion, the present study revealed that headache frequency was not significantly different between JME patients and healthy controls (p > 0.05). However, migraine frequency was higher in JME patients than healthy controls. Some migraine and TTH characteristics were different in between groups. We suggest that our results support both genetic relationship and shared underlying hypothetical pathopysiological mechanisms between JME and headache, especially migraine.

Prevalence of juvenile myoclonic epilepsy in people <30 years of age-A population-based study in Norway.

OBJECTIVE: Despite juvenile myoclonic epilepsy (JME) being considered one of the most common epilepsies, population-based prevalence studies of JME are lacking. Our aim was to estimate the prevalence of JME in a Norwegian county, using updated diagnostic criteria. METHODS: This was a cross-sectional study, based on reviews of the medical records of all patients with a diagnosis of epilepsy at Drammen Hospital in the period 1999-2013. The study population consisted of 98,152 people <30 years of age. Subjects diagnosed with JME, unspecified genetic generalized epilepsy, or absence epilepsy were identified. All of these patients were contacted and asked specifically about myoclonic jerks. Electroencephalography (EEG) recordings and medical records were reevaluated for those who confirmed myoclonic jerks. Information about seizure onset was obtained from the medical records, and annual frequency of new cases was estimated. RESULTS: A total of 55 subjects fulfilled the diagnostic criteria for JME. The point prevalence was estimated at 5.6/10,000. JME constituted 9.3% of all epilepsies in the age group we investigated. Of subjects diagnosed with either unspecified genetic generalized epilepsy or absence epilepsy, 21% and 12%, respectively, had JME. We identified 21 subjects with JME (38%) who had not been diagnosed previously. Six subjects (11%) had childhood absence epilepsy evolving into JME. Between 2009 and 2013, the average frequency of JME per 100,000 people of all ages per year was estimated at 1.7. SIGNIFICANCE: A substantial portion of people with JME seem to go undiagnosed, as was the case for more than one third of the subjects in this study. By investigating subjects diagnosed with unspecified genetic generalized epilepsy or absence epilepsy, we found a prevalence of JME that was considerably higher than previously reported. We conclude that JME may go undiagnosed due to the underrecognition of myoclonic jerks. To make a correct diagnosis, clinicians need to ask specifically about myoclonic jerks.

Exploring psychiatric comorbidities and their effects on quality of life in patients with temporal lobe epilepsy and juvenile myoclonic epilepsy.

AIM: The relation of epilepsy with psychiatric disorders is of great interest to researchers due to its behavioral, social, and cognitive outcomes. In this study, we explored psychiatric comorbidity and its effects on quality of life (QOL) in patients with mesial temporal lobe epilepsy (MTLE) and juvenile myoclonic epilepsy (JME). METHODS: Thirty patients with MTLE, 30 patients with JME, and 30 healthy controls underwent the Structured Clinical Interview for DSM-IV (SCID-I) to diagnose psychiatric disorders. None of the subjects had previously undergone psychiatric examination. The Quality of Life in Epilepsy Inventory-89 (QOLIE-89) was used to assess QOL. We compared psychiatric comorbidity among groups and evaluated its effects on QOL. RESULTS: We detected comorbid psychiatric disorders in 37% of patients with JME and in 57% of patients with MTLE. Comorbid psychiatric disorders were less frequent in healthy controls compared to the patient groups (P = 0.029). Comparing demographic and clinical features of patients with JME and MTLE and their mean QOL scores, there was no statistical difference. Furthermore, we compared QOLIE scores between patients with and without psychiatric comorbidity. JME patients with mood disorders had lower scores on the Attention/Concentration subscale (P = 0.013). MTLE patients with a psychotic disorder had lower scores on the Social Isolation, Energy, and Fatigue subscales (P = 0.045). Patients with somatoform disorders had higher Pain scores (P = 0.04). CONCLUSION: Our study suggests that comorbid psychiatric disorders negatively affect patients' QOL regardless of seizure syndrome. Comorbid psychiatric conditions should be determined to increase QOL in patients with epilepsy.

Status epilepticus in patients with juvenile myoclonic epilepsy: Frequency, precipitating factors and outcome.

Status epilepticus (SE) is rarely described in patients with juvenile myoclonic epilepsy (JME), and little is known about its frequency, subtypes, and predictors and the prognosis of these patients. In this retrospective study, we aimed to analyze the incidence of SE in patients with JME and emphasize the risk factors and long-term outcome of SE in an epilepsy outpatient-based cohort. We included patients with JME with a history of predominant myoclonic seizures and at least one diagnostic EEG with normal background activity and bursts of typical ≥3-Hz generalized spike-polyspike and waves. We investigated the electroclinical features of patients with JME who had experienced SE and compared them with patients with JME without SE. Of the 133 patients with JME, only 5 patients were diagnosed with SE (3.8%) according to new criteria. The most common SE subtype was myoclonic SE (MSE, 4 patients), followed by generalized clonic-tonic-clonic SE (1 patient) and nonconvulsive SE (1 patient). One patient had both MSE and generalized clonic-tonic-clonic SE. In three out of five patients, recurrent episodes of SE were observed. Same seizure precipitants including sleep deprivation, inappropriate antiepileptic drug treatment, and noncompliance were identified in patients with JME with and without SE, not reaching a significant difference between the groups. Myoclonia limited to specific body parts (one arm, face, or head) were significantly more common in patients with JME with SE (p: 0.002). We did not find any significant correlation with drug-resistant course and SE. Status epilepticus is rarely observed in patients with JME, and MSE appears to be the most common subtype. Local myoclonia might predict SE in a subgroup of patients with JME. We may suggest that some patients with JME have a liability to SE, in addition to usual seizure precipitating factors of JME. It seems that SE per se does not affect the outcome of JME and the patients with SE did not have drug-resistant course in the final analysis.

Delineating behavioral and cognitive phenotypes in juvenile myoclonic epilepsy: Are we missing the forest for the trees?

INTRODUCTION: Patients with juvenile myoclonic epilepsy (JME) have executive dysfunction and impulsive traits. There are lines of evidence that JME is a heterogeneous epilepsy syndrome considering outcome. In this study, we aimed to analyze this heterogeneity beyond seizure control. The objective was to identify whether the pattern of cognitive dysfunction and impulse control is also heterogeneous, in an attempt to establish possible differences in patients with easy- and hard-to-control epilepsies. METHODS: Essentially, 57 patients with JME were compared with 44 controls. Patients and controls were assessed with a neuropsychological battery for executive, attention, and memory functions. The expression of impulsive traits was evaluated with the Temperament and Character Inventory - novelty seeking domain. Then, patients were categorized according to seizure control as having easy- and hard-to-control JME. RESULTS: Patients with hard-to-control JME showed worse performance in 12 out of 25 neuropsychological tests than those with easy-to-control JME. Patients with hard-to-control JME also demonstrated significantly higher scores in novelty seeking - subfactor impulsiveness (p=0.002). SIGNIFICANCE: Our study demonstrated the existence of distinct or more severe cognitive and psychiatric profiles in a subset of patients with JME. Patients with treatment-refractory seizures seem to present a broader impairment related to both cognitive deficits and impulsive traits. These findings suggest that patients with JME are not equally compromised by executive and memory deficits or dysfunction, neither by their impulsive traits. Thus, there is a need for a better characterization of patients with JME to include diverse phenotypes since our results suggest a possible existence of distinct groups of patients with JME.

Psychiatric disorders among 165 patients with juvenile myoclonic epilepsy in India and association with clinical and sociodemographic variables.

OBJECTIVE: The current study evaluated the association between clinical variables and psychiatric disorders (PDs) in patients with juvenile myoclonic epilepsy (JME). METHODS: Consecutive patients with JME who had at least two years of regular follow-up from May 2011 to April 2014 formed the study population. The association between clinical and sociodemographic data with psychiatric evaluation on structured clinical interview and quality of life in epilepsy - 31 (QOLIE-31) was evaluated using logistic regression analysis. RESULTS: Out of 165 patients in the current study, 77 (46.6%) patients were diagnosed with PDs; while 50 were categorized to having anxiety disorders, 27 patients had depressive disorders. The mean age of the study population was 25.35 ± 7.6 years with 37.52% women. Patients with PDs had lower overall QOLIE score (55.84 ± 13.07 vs 68.70 ± 11.23, p<0.001) and lower social function score (80.95 ± 19.22 vs 91.09 ± 14.74, p<0.001). Being married was the strongest predictor of depressive disorders (ß=8.59; 95% CI, 1.44-51.28; p=0.018); whereas, lower emotional well-being (ß=0.942; 95% CI, 0.907-0.978; p=0.002) was the only variable associated with anxiety disorders. Patients with depressive disorders had longer duration of PDs (11.85 ± 8.68 years vs 7.75 ± 6.70 years, p=0.039), and a majority of them were married (66.7% vs 26.0%, p=0.001). Patients with depressive disorders scored low on emotional well-being (50.81 ± 14.62 vs 61.02 ± 13.05, p=0.002), energy levels (52.78 ± 11.71 vs 62.80 ± 10.84, p<0.001), and social function (70.96 ± 20.69 vs 86.34 ± 16.16, p=0.001). Depressive disorders were more prevalent among married patients above 35 years of age (5.2% vs 36.8%, p=0.042). SIGNIFICANCE: Nearly half of the patients with JME had coexisting PDs. The psychological profile of anxiety disorders was different from depressive disorders in patients with JME. Depressive disorders were more prevalent among older patients with JME, and marriage was strongly associated with depressive disorders.

Epidemiology and clinical manifestations of juvenile myoclonic epilepsy (JME) in Iran.

Because most descriptive studies did not specifically analyze the syndromes of idiopathic generalized epilepsy (IGE), including juvenile myoclonic epilepsy (JME), epidemiologic data concerning these syndromes are scarce or often unreliable. In this retrospective chart review study, all patients with a clinical diagnosis of JME were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, from 2008 to 2013. Demographic variables and relevant clinical and EEG variables were summarized descriptively. 2,750 patients with epilepsy were registered at our epilepsy clinic; 239 patients (8.7 %) were diagnosed as having JME. Female to male ratio was 1.7. Age at seizure onset was 15 ± 3.5 years. Generalized tonic-clonic seizures were reported by 225 patients (94.1 %) and absences by 90 (37.6 %). Electroencephalography (EEG) was abnormal in 69.6 % of the patients. JME is one of the most common syndromes of IGEs. The key element in making the correct diagnosis is obtaining a detailed clinical history. MRI or laboratory tests in a patient, in whom you are suspecting JME are not necessary. Even EEG has some limitations and normal or even atypical findings in a patient with typical history for JME should not deter from the correct diagnosis.

Psychosocial long-term outcome in juvenile myoclonic epilepsy.

PURPOSE: Juvenile myoclonic epilepsy (JME) is a well-defined subsyndrome of idiopathic generalized/genetic epilepsy. It is allegedly related to specific personality characteristics and has been associated with unfavorable social outcome. We aimed to analyze psychosocial outcome in patients with JME. To delineate consequences of the chronic seizure disorder from possible neurobiologic contributions being inherent to the condition itself, we compared social outcome in JME subjects with that of age- and sex-matched control patients with absence epilepsy (AE). METHODS: Patients with an epilepsy course of at least 20 years were included. All JME and AE patients (n = 41 in each group) answered a structured questionnaire asking about seizures, treatment, and psychosocial variables. In addition, patients with JME were assessed with the Quality of Life in Epilepsy Inventory 31 (QOLIE-31). RESULTS: In JME, 46.3 years (20-69) after onset of epilepsy, the overall psychosocial long-term outcome was favorable (80.5% of patients had never been unemployed for more than 1 year, 90.2% were well integrated into social context). Quality of life in all inquired subdomains revealed high scores. Compared with AE controls, JME patients did not perform worse regarding psychosocial outcome; rate of university access and degrees in JME patients was even higher (70% vs. 34%, p = 0.001). JME patients showed a high level of quality of life, and current or previous psychiatric comorbidity was associated significantly with lower overall quality of life scores (p = 0.02). SIGNIFICANCE: Our long-term study on JME patients demonstrated favorable psychosocial outcome that contrasted previous findings. This is the first study to compare social outcome in JME with another genetically determined form of epilepsy. Similar outcomes in JME and AE patients argue against specific neurobiologic alterations in JME that may predispose to social deficits. In JME, reduced quality of life seems to be associated with psychiatric comorbidity.

Impact of family support on psychiatric disorders and seizure control in patients with juvenile myoclonic epilepsy.

OBJECTIVE: Psychiatric disorders (PDs) are frequently observed in patients with juvenile myoclonic epilepsy (JME). In this study, we aimed to assess factors associated with PDs in patients with JME. METHODS: Retrospective analysis of data of 90 consecutive patients with JME was performed. Assessment of DSM-IV Axis I clinical disorders was done using Structured Clinical Interview for Axis I. Diagnosis of PDs is made when the score exceeds the threshold provided by the DSM-IV. We also applied the Global Assessment of Functioning (GAF) scale which is part of the multiaxial evaluation of the DSM-IV (Axis-V). Using seizure frequency score at presentation, we classified subjects into controlled and uncontrolled groups. RESULTS: In the current cohort, 29 (32.2%) patients were diagnosed with PDs. Fewer patients with PDs had family support (48.3% vs. 83.6%; p=0.001). Lifetime prevalence of PDs was higher among patients with current PDs (96.6% vs. 18.0%; p<0.0001). Subthreshold illness was not different between the groups (17.2% vs. 27.9%; p=0.204). Mean GAF was higher in patients without PDs than in patients with PDs (89.19±6.92 vs. 64.22±9.76; p<0.0001). Patients with PDs had lower seizure control (7.8% vs. 73.1%; p<0.0001) compared with patients without PDs. Logistic regression analysis for factors associated with diagnosis of PDs revealed that none of the factors significantly affected the odds of seizure control. Patients with lack of family support had poor seizure control (0% vs. 36.9%; p<0.0001); 51.7% of patients with JME with PDs reported lack of family support. Patients with family support had lower lifetime prevalence of PDs (30.8% vs. 76.0%; p<0.0001), whereas patients with JME without family support had lower levels of education (8.0% vs. 35.4%; p=0.009). CONCLUSION: Lack of family support is associated with poor seizure control and higher incidence of PDs in patients with JME. Lack of family support increases neither the odds of PDs nor seizure control.

A systematic review and meta-analysis of factors related to first line drugs refractoriness in patients with juvenile myoclonic epilepsy (JME).

INTRODUCTION: Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its hallmark features encompass unprovoked bilateral myoclonus and tonic-clonic seizures that manifest during adolescence. While most JME patients respond favorably to anti-seizure medication (ASM), a subset experiences refractory JME, a condition where seizures persist despite rigorous ASM treatment, often termed "Drug-Resistant Epilepsy" (DRE). This systematic review and meta-analysis aims to determine the prevalence of refractory JME, and further to identify socio-demographic, electrophysiological and clinical risk factors associated with its occurrence. Pinpointing these factors is crucial as it offers the potential to predict ASM responsiveness, enabling early interventions and tailored care strategies for patients. MATERIAL AND METHODS: The systematic review and meta-analysis followed the Cochrane Handbook and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study evaluated outcomes post ASM treatment in JME cohorts by searching papers published up to September 2023 in PubMed/MEDLINE, Scopus, and Google Scholar databases. Predefined inclusion criteria were met by 25 eligible studies, forming the basis for analysis. RESULTS: A total of 22 potential risk factors for refractory JME were documented. Notably, robust risk factors for treatment resistance included Psychiatric Disorder (Odds Ratio (OR), 3.42 [2.54, 4.61] (95% Confidence Inverval (Cl)), Febrile Seizures (OR, 1.83 [1.14, 2.96] (95% Cl)), Alcohol Consumption (OR, 16.86 [1.94, 146.88] (95%Cl)), Aura (OR, 2.15 [1.04, 4.47] (95%Cl)), childhood absence epilepsy (CAE) evolving into JME (OR, 4.54 [1.61, 12.78] (95%CI)), occurrence of three seizure types (OR, 2.96 [1.96, 4.46] (95%CI)), and Focal EEG abnormalities (OR, 1.85 [1.13, 3.01] (95%Cl)). In addition, there were some non-significant risk factors for DRE because of noticeable heterogeneity. CONCLUSION: In aggregate, over 36% of JME patients demonstrated drug resistance, with seven significant risk factors closely linked to this refractoriness. The interplay between these factors and whether they denote treatment non-response or heightened disease burden remains an open question and more studies would be required to fully examine their influence.

Epidemiology of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a widely recognized presumed genetic, electroclinical idiopathic generalized epilepsy syndrome. The prevalence of JME in large cohorts has been estimated to be 5% to 10% of all epilepsies and around 18% of idiopathic generalized epilepsies but may be lower in some settings. There is a marked female predominance. However, some of the basic epidemiology of JME is not well known, possibly because the syndrome is not sharply defined. A questionnaire study about the diagnostic criteria for JME suggests that diagnosis of JME can be made with the history of myoclonus plus a single generalized tonic-clonic seizure plus generalized fast spike-waves or polyspike-waves on the EEG. However, until these diagnostic criteria are fully accepted, the detailed epidemiology of JME will remain imprecise.

Juvenile myoclonic epilepsy: psychiatric comorbidity and impact on outcome.

Juvenile myoclonic epilepsy (JME) is a well-defined age-related idiopathic epilepsy syndrome. Past studies have emphasized the difficulties in the treatment of patients with JME, which have been attributed to some specific psychiatric, psychological, and psychosocial characteristics. These aspects have aroused a significant amount of interest in the last two decades. In this article, the available studies that investigated the prevalence of psychiatric disorders (PDs) in JME and its impact on seizure outcome were reviewed in order to provide an update to clinicians about these two important aspects associated with this common epilepsy syndrome. The review disclosed a high prevalence of PDs in patients with JME, particularly mood, anxiety, and personality disorders. In addition, most recent studies have also observed that overall prevalence of PDs in JME has not shown statistically significant differences when compared with TLE, an epilepsy syndrome where the psychiatric aspects are most frequently studied. Taken together, data regarding the prevalence of PDs and their possible consequences on seizure outcome on JME indicate that special attention should be directed to psychological disturbances and psychiatric symptoms in this epilepsy syndrome. The early recognition and treatment of psychiatric symptoms, as well as psychological disturbances and psychosocial difficulties, should be considered fundamental to JME prognosis.

Chronodependency and provocative factors in juvenile myoclonic epilepsy.

In juvenile myoclonic epilepsy (JME), occurrence of seizures and epileptiform EEG discharges is influenced by internal and external factors. The most important internal factor is the chronodependency: the occurrence of myoclonic jerks in the early morning is one of the hallmarks of JME. Approximately two-thirds of the patients with JME report that seizures are provoked by a variety of general factors like stress, fatigue, fever, and sleep and more specific precipitants like flashing sunlight, music, reading, thinking, and excess alcohol. The prevalence rate of photosensitivity (photoparoxysmal EEG response) in patients with JME ranges from 8 to 90%; it is seen more often in females and adolescents and depends on drug use. Since both JME and photosensitivity are connected with generalized types of epilepsy and myoclonus, the two traits are comorbid for that reason. Epileptiform EEG discharges can be provoked by other activation methods: sleep, hyperventilation, and specific cognitive tasks. Attention seems to have a non-specific, inhibitory effect of the epileptiform discharges. Hyperventilation can induce absence seizures in patients with JME, while cognitive tasks are efficient in precipitating myoclonic seizures. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?