Unsupervised clustering of a deeply phenotyped cohort of adults with idiopathic generalized epilepsy.

Objective: Idiopathic generalized epilepsy (IGE) in adults comprise juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic-clonic seizures alone (EGTCS), which are defined by their seizure types but also cover a broad endophenotype of symptoms. Controversy exists on whether adult IGE is a group of distinct diseases or a clinical spectrum of one disease. Here, we used a deeply phenotyped cohort to test the hypothesis that IGE comprises three distinct clinical entities.

Prodromal Phase of Idiopathic Generalized Epilepsy: A Register-Based Case Control Study.

Background And Objectives: Idiopathic generalized epilepsy (IGE) is associated with distinct behavioral traits, symptoms of frontal lobe dysfunction, and psychiatric comorbidity. Whether psychiatric symptoms are part of the IGE endophenotype or secondary to the burden of chronic disease is unknown. In this study, we aimed at describing the sequence of appearance of psychiatric and epilepsy symptoms in patients with IGE.

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE).

Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.

Objective: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients.

Methods: In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included.

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy.

Importance: After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients.

Objective: To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE.

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model.

Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications.

Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes.

Association of symptoms of psychiatric disease and electroencephalographic patterns in idiopathic generalized epilepsy.

Objective: Idiopathic generalized epilepsies (IGE) are genetic epilepsies with alterations of thalamo-frontocortical circuits that play a major role in seizure generation and propagation. Psychiatric diseases and drug resistance are strongly associated, but it remains unknown if they are symptoms of the same pathophysiological process. Hypothesizing that the same network alterations are associated with the frequency of epileptic discharges (ED) and psychiatric symptoms, we here tested the association of self-reported psychiatric symptoms and IGE severity estimated by electroencephalographic (EEG) biomarkers.

Neuropsychological profile and drug treatment response in Idiopathic Generalized Epilepsy.

Purpose: The endophenotype of Idiopathic Generalized Epilepsies (IGE) comprises distinct neuropsychological deficits compared to normal controls. It is unknown if the severity of features of the endophenotype correlates with resistance to anti-seizure medication. Therefore, we here studied the association of neuropsychological profiles with treatment response.

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment.

Drug resistance in idiopathic generalized epilepsies: Evidence and concepts.

Although approximately 10%-15% of patients with idiopathic generalized epilepsy (IGE)/genetic generalized epilepsy remain drug-resistant, there is no consensus or established concept regarding the underlying mechanisms and prevalence. This review summarizes the recent data and the current hypotheses on mechanisms that may contribute to drug-resistant IGE. A literature search was conducted in PubMed and Embase for studies on mechanisms of drug resistance published since 1980.

Salzburg consensus criteria are associated with long-term outcome after non-convulsive status epilepticus.

Purpose: To investigate differences in long-term survival and short-term neurological deficits in adult patients fulfilling either sub-criterion of the Salzburg Consensus Criteria (SC) for non-convulsive status epilepticus (NCSE).

Methods: We retrospectively identified a cohort of patients with first-time NCSE epilepticus at Odense University Hospital from 2014 to 2017. Results of electroencephalograms at admission were dichotomized according to the SC (more than 25 epileptiform discharges/10 s was defined as the fast criterion), and groups were compared statistically through survival analysis and in a logistic regression model adjusting for established prognostic determinants in status epilepticus.

Pseudoresistance in idiopathic/genetic generalized epilepsies - Definitions, risk factors, and outcome.

Objective: The aim of the study was to determine risk factors associated with pseudoresistance in a large, representative cohort of patients with Idiopathic/Genetic Generalized Epilepsy (IGE) and the impact of pseudoresistance on socioeconomic parameters.

Methods: We performed a literature review on definitions of pseudoresistance in IGE. In an established cohort of patients with IGE from Funen, patients with current or previous pseudoresistant seizures were retrospectively identified based on a comprehensive evaluation of the patients' medical records and direct patient contact, if required.

Sex-specific disease modifiers in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.

The burden of disease of idiopathic/genetic generalized epilepsy - A nationwide online survey.

The aim of the study was to assess the self-reported burden of disease in people with idiopathic/genetic generalized epilepsy and risk factors associated with high disease burden. We performed a nationwide online survey on epilepsy characteristics/treatment, quality of life/daily living followed by Standardized Assessment of Personality-Abbreviated Scale, Major Depression Inventory, Barratt Impulsiveness Scale (brief) and the brief Epilepsy Anxiety Survey Instrument. The survey was sent to 275 representative patients with IGE ('Funen cohort') and later publicly distributed via the Danish Epilepsy Association.

Magnetic evoked potential polyphasia in idiopathic/genetic generalized epilepsy: An endophenotype not associated with treatment response.

Objective: Increased Motor Evoked Potential (MEP) polyphasia was recently described in idiopathic/genetic generalized epilepsy (IGE). Here, we studied the association of MEP polyphasia with treatment response and other clinical characteristics in patients with IGE.

Methods: MEPs were recorded from the biceps brachii, flexor carpi radialis and interosseus dorsalis muscles bilaterally during tonic contraction in IGE patients (n = 72) and historical controls (n = 54) after single pulse transcranial magnetic stimulation.

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.

Risk factors of paradoxical reactions to anti-seizure medication in genetic generalized epilepsy.

This study aimed at providing valid estimates for the risk of clinically relevant seizure aggravation by recommended anti-seizure medications in patients with Genetic Generalized Epilepsy (GGE). To this aim, treatment response, side effects and paradoxical reactions to anti-seizure treatment were retrospectively assessed in a near-population based cohort comprising 471 adult GGE patients. A total of 1046 treatment attempts were analyzed (lamotrigine: 351, valproic acid: 295, levetiracetam: 249, primidone/phenobarbital: 94, zonisamide: 57).

Trait impulsivity in Juvenile Myoclonic Epilepsy.

Objective: Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta-analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs).

Patterns and prognostic markers for treatment response in generalized epilepsies.

Objective: To determine the pattern of treatment response in patients with idiopathic generalized epilepsy (IGE) and whether routinely assessed clinical and neurophysiological parameters allow predicting response to lamotrigine, levetiracetam, or valproic acid.

Methods: In 328 adult patients with IGE, demographic data, imaging, EEG data, current and prior antiepileptic treatment, treatment outcome, and side effects were analyzed from the patients' medical files and patient interviews.

Results: Seizure freedom with acceptable side effects at the first attempt was achieved in 61 (18.

The clinical spectrum of familial and sporadic idiopathic generalized epilepsy.

Objective: Although the genetic origin of Idiopathic/Genetic Generalized Epilepsy (IGE) is hardly disputed, only a minority of patients show Mendelian inheritance. We here questioned if clinical characteristics like long-term outcome and treatment response differ between patients with sporadic and familial IGE.

Methods: In a near-population based cohort of IGE patients, clinical characteristics, treatment response and family history of 443 IGE patients were analyzed.

Prognostic Value of Generalized Polyspike Trains and Prolonged Epileptiform EEG Runs.

Introduction: A considerable proportion of patients with genetic/idiopathic generalized epilepsy (IGE) suffer from persistent seizures. In this study, it was questioned if generalized polyspike trains (GPT) or prolonged epileptiform EEG runs allow identification of difficult-to-treat patients in a first seizure clinic setting or after recurrent seizures.

Methods: The first routine outpatient EEGs from untreated patients (later diagnosed with IGE) and routine EEGs from IGE patients with persistent seizures despite medical treatment were analyzed.

High long-term mortality after incident status epilepticus in adults: Results from a population-based study.

Objective: To determine annual incidence, etiology, severity, and short- and long-term mortality of first-time, nonanoxic status epilepticus (SE) in adults in a population-based retrospective cohort study.

Methods: We systematically identified all episodes of SE in the year 2014 on the island of Funen. Patients with SE due to anoxia, patients with recurrent SE, and patients <18 years old were excluded.