Elza Márcia Targas Yacubian

Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy

Objective: To evaluate the efficacy and safety of ezogabine (United States adopted name)/retigabine (international nonproprietary name) (EZG[RTG]) 1,200 mg/day as adjunctive treatment in adults with drug-resistant epilepsy with partial-onset seizures with or without secondary generalization. Methods: RESTORE 1 was a multicenter, randomized, double-blind, parallel-group trial. Following a prospective 8-week baseline phase, patients entered an 18-week double-blind treatment period (6-week forced dose titration to EZG[RTG] 1,200 mg/day in 3 equally divided doses or placebo, followed by a 12-week maintenance phase). Results were analyzed on an intent-to-treat basis for the entire 18-week period and for patients reaching the maintenance phase. Results: In 306 patients randomized, 305 received EZG(RTG) 1,200 mg/day (n = 153) or placebo (n = 152). Median percent reduction in total partial-seizure frequency was 44.3% vs 17.5% (p < 0.001) for EZG(RTG) and placebo, respectively, during the 18-week double-blind period; responder rates (≥50% reduction in total partial-seizure frequency from baseline) were 44.4% vs 17.8% (p < 0.001). In 256 patients (EZG[RTG], 119; placebo, 137) entering the 12-week maintenance phase, median percent reduction in seizure frequency for EZG(RTG) vs placebo was 54.5% and 18.9% (p < 0.001), respectively; responder rates were 55.5% vs 22.6% (p < 0.001). The proportion of patients discontinuing due to treatment-emergent adverse events (TEAEs) was 26.8% (EZG[RTG]) vs 8.6% (placebo). Dizziness, somnolence, fatigue, confusion, dysarthria, urinary tract infection, ataxia, and blurred vision were the most common TEAEs reported by more patients treated with EZG(RTG) than placebo. Conclusions: This study demonstrates that EZG(RTG) is effective as add-on therapy for reducing seizure frequency in patients with drug-resistant partial-onset seizures. Classification of evidence: This study provides Class II evidence that EZG(RTG) 1,200 mg/day is effective as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization.

Neuropsychological profile of patients with juvenile myoclonic epilepsy: A controlled study of 50 patients

The purpose of this study was to verify possible cognitive dysfunction in patients with juvenile myoclonic epilepsy (JME) and its relationship to factors related to epilepsy and schooling. Fifty subjects diagnosed with JME and 50 controls underwent neuropsychological assessment evaluating intellectual functions, attention, memory, executive functions, and language. The patients were further divided into two subgroups on the basis of educational level: < or = 11 and >11 years of formal education. Participants diagnosed with JME scored significantly below age-, education-, and gender-matched controls on neuropsychological measures of attention, immediate verbal memory, mental flexibility, control of inhibition, working memory, processing speed, verbal delayed memory, visual delayed memory, naming, and verbal fluency. A positive correlation was observed between duration of epilepsy and cognitive decline. However, in the group of patients with >11 years of education, this correlation was not significant. In this series of patients with JME, neuropsychological evaluation suggests widespread cognitive dysfunction outside the limits of the frontal lobes. The duration of epilepsy correlated with cognitive decline, and patients with higher education manifested less progression of deficits.

Self-perception of factors that precipitate or inhibit seizures in juvenile myoclonic epilepsy

PURPOSE To assess self-perception of factors that precipitate or inhibit seizures in patients with juvenile myoclonic epilepsy (JME). PATIENTS AND METHODS Thirty-six males and 39 females with JME and mean age of 25.8+/-8.7 years were analysed. All patients completed a standardized questionnaire to assess for the presence or absence of precipitant or inhibitory factors for their seizures in a face-to-face interview. These data were statistically analysed through logistic and linear regression models and Phi coefficient. RESULTS Ninety-two percent of the patients identified at least one precipitating factor (PF). In order of frequency the following PFs were recorded: stress (83%), sleep deprivation (77%), specific thoughts/mental concentration (23%), performance of hand activities and complex finger movements (20%), flashing lights and playing games (15%), speaking out in public (11%) and alcohol intake (11%), reading (7%), calculating and writing (5%), playing musical instruments (4%), drawing (3%), and specific types of music (1%). Menstrual cycle was the third most important PF in the women (33%). Although PFs were easily recognized, 77% of the patients stated that they were unable to avoid the occurrence of the seizures. CONCLUSIONS Structured questionnaire is useful in stimulating patients to self-report seizure precipitants. Patients with higher education and uncontrolled seizures identified them more easily. The presence of a significant number of uncommon PFs, such as mental and motor hand tasks, considered uncommon for other epileptic syndromes, suggests that the role of these factors may be under-recognized in JME.

Psychiatric disorders in juvenile myoclonic epilepsy: A controlled study of 100 patients

In this controlled study we evaluated the frequency of psychiatric disorders (PDs) in 100 patients with juvenile myoclonic epilepsy (JME) and compared it with that of 100 healthy controls matched with respect to age, gender, schooling, and socioeconomic status. Our aim was to quantify the frequency of PDs and evaluate the relationship between PDs and factors related to epilepsy. Subjects were evaluated with the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I) and Axis II disorders (SCID-II). Patients with JME presented with significantly more PDs (P<0.01) and psychosocial problems (P<0.01) than the controls. PDs were diagnosed in 49 patients with JME. Anxiety and mood disorders, present in 23 and 19 patients, respectively, were the most frequently observed. Twenty patients fulfilled criteria for personality disorders; 17 (85%) patients had cluster B personalities comprising the behavioral characteristics impulsivity, humor reactivity, emotional instability, and difficulty in accepting social rules, similar to those cited in the earliest mentioned description of this syndrome. PDs were more frequently observed in patients with higher seizure frequency (P<0.05).

Hyperventilation Revisited: Physiological Effects and Efficacy on Focal Seizure Activation in the Era of Video‐EEG Monitoring

Summary:  Purpose: Hyperventilation is an activation method that provokes physiological slowing of brain rhythms, interictal discharges, and seizures, especially in generalized idiopathic epilepsies. In this study we assessed its effectiveness in inducing focal seizures during video‐EEG monitoring.

Instruction manual for the ILAE 2017 operational classification of seizure types

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor‐onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic–clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic–atonic, myoclonic–tonic–clonic, tonic, or tonic–clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic–clonic, epileptic spasms, or behavior arrest. This “users’ manual” for the ILAE 2017 seizure classification will assist the adoption of the new system.

Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis

OBJECTIVE We assessed the cognitive performance of patients with temporal lobe epilepsy (TLE) caused by unilateral hippocampal sclerosis (HS), in comparison with that of matched, healthy controls. We report the relationship between cognitive measures and duration of epilepsy, correlating with hippocampal volumes, and the impact of educational level on cognitive decline. METHODS This study involved 61 outpatients (40 with < or = 8 years and 21 with >8 years of formal education) with unilateral HS and 61 controls. Volumetric MRI was performed on all patients and 10 controls. The results (mean, SD) of the neuropsychological tests of healthy subjects and patients were compared using the Student t and Mann-Whitney tests. RESULTS Patients performed worse than controls in the neuropsychological evaluation. When adjusted z scores were used to calculate the impairment index, patients had a greater percentage of abnormal tests compared with controls. The cognitive decline, assessed through the impairment index, correlated with duration of epilepsy. Higher level of education did not protect against this decline, thus not supporting the hypothesis of cerebral reserve in this population. A significant correlation between hippocampal volumetric measures and duration of epilepsy was observed only in patients with left HS. CONCLUSION Patients with TLE caused by HS present with cognitive morbidity that extends beyond memory deficits. Cognitive decline is associated with duration of epilepsy, and in patients with left-sided HS, duration may correlate with volumetric hippocampal loss.

Magnetic resonance spectroscopy reveals an epileptic network in juvenile myoclonic epilepsy

Purpose:  To investigate the cerebral metabolic differences between patients with juvenile myoclonic epilepsy (JME) and normal controls and to evaluate to what extent these metabolic alterations reflect involvement of an epileptic network.

Neuropsychiatric profiles of patients with juvenile myoclonic epilepsy treated with valproate or topiramate.

In this cross-sectional study, the neuropsychiatric profiles of 42 patients with juvenile myoclonic epilepsy (JME) who were treated with valproate (VPA) or topiramate (TPM) in monotherapy were compared with the aim of verifying the relationship between cognitive dysfunction, psychiatric disorders, and factors related to epilepsy. Patients with JME taking VPA 500-1750 mg/day or TPM 50-175 mg/day were selected. For all patients, psychiatric profiles were evaluated with the Scheduled Clinical Interview, axes I and II (SCID I and SCID II), or the Brazilian version of the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS-PL). Neuropsychological measures included intellectual functions, attention, memory, executive functions, and language. Patients taking TPM exhibited worse neuropsychological performance on attention, short-term memory, processing speed, and verbal fluency functions related to frontal lobes, which may be dysfunctional in JME. Anxiety disorders were associated with lack of seizure control and having had more than 20 lifetime generalized tonic-clonic seizures.

Validity and reliability of the Portuguese version of the quality of life in epilepsy inventory (QOLIE-31) for Brazil

PURPOSE We report the cultural adaptation and psychometric properties of the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) for the Portuguese language and Brazilian culture. METHODS This study involved 150 outpatients: 50 presurgical patients with refractory temporal lobe epilepsy (TLE) related to mesial temporal sclerosis (MTS), 50 patients with juvenile myoclonic epilepsy (JME), and 50 seizure-free patients with TLE. They completed the QOLIE-31, Nottingham Health Profile (NHP), Beck Depression Inventory (BDI), and Adverse Events Profile (AEP) and underwent a neuropsychological evaluation (NE). Internal consistency reliability, interrater and test-retest reliability, and construct validity were assessed. RESULTS QOLIE-31 mean scores were 33.1 (Social Function), 68.9 (Overall Quality of Life), 56.5 (Seizure Worry), 64.1 (Emotional Well-Being), 63.7 (Energy/Fatigue), 38.9 (Cognitive Function), and 49.7 (Medication Effects). Internal consistency was high (Cronbachs alpha), as were the associations between QOLIE-31 and the BDI, NHP, AEP, and NE. CONCLUSION The Portuguese/Brazilian version of the QOLIE-31 inventory showed good reliability, validity, and construct validity.