Laura Maria de Figueiredo Ferreira Guilhoto

ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology

The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self‐limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.

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.

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).

Magnetic resonance spectroscopy reveals an epileptic network in juvenile myoclonic epilepsy

Purpose:u2002 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.

Prognosis of juvenile myoclonic epilepsy is related to endophenotypes

PURPOSEnTo investigate if phenotypic variations have prognostic implications in juvenile myoclonic epilepsy (JME).nnnMETHODSnSixty-five consecutive JME patients had video-EEG recording and were followed for at least three years. Reflex traits were defined as seizures and/or EEG discharges induction by eye-closure, photic stimulation, language, praxis or calculation. Patients had psychiatric evaluation and answered to STAI (State-Trait Anxiety Inventory). Seizure control was classified according to Prasad et al. (2003).(24) Patients were divided into Group 1: good seizure control and Group 2: moderate or poor seizure control. Video-EEG/EEG evaluation was repeated in 21 patients.nnnRESULTSnForty of 65 (61.5%) patients reached good seizure control, 25 (38.5%) of whom became seizure free. Group 2 patients had longer epilepsy duration (13.9±9.0 vs. 8.7±8.2; p=0.019); higher prevalence of the combination of all three seizure types (72.0% vs. 30.0%; p=0.003); discharges in baseline EEG (56.0% vs. 22.5%; p=0.008); seizure recording (68% vs. 20%; p<0.001) and sensitivity to praxis (63.6% vs. 29.6%; p=0.023). Compared to seizure-free patients, those with persistent seizures presented younger age at epilepsy onset (12.6±3.33 years vs. 15.4±5.47 years; p=0.015); higher prevalence of personality disorders (25% vs. 4%; p=0.029); higher scores in STAI-T (45.9±11.31 vs. 36.6±11.43; p=0.011) and higher incidence of sensitivity to praxis (58.6% vs. 25.0%; p=0.04) and to language (53.8 vs. 16.7%; p=0.026) tasks. Repetition of EEG/video-EEG revealed a parallel evolution of reflex traits disappearance and seizure control.nnnDISCUSSIONnClinical features and reflex traits have prognosis implications in JME.

Provocative and inhibitory effects of a video-EEG neuropsychologic protocol in juvenile myoclonic epilepsy

Purpose:u2002 Studies suggest that higher cognitive functions could precipitate seizures in juvenile myoclonic epilepsy (JME). The present study aimed to analyze the effects of higher mental activity on epileptiform discharges and seizures in patients with JME and compare them to those of habitual methods of activation.

Personality traits related to juvenile myoclonic epilepsy: MRI reveals prefrontal abnormalities through a voxel-based morphometry study.

Studies involving juvenile myoclonic epilepsy (JME) patients have demonstrated an elevated prevalence of cluster B personality disorders (PD) characterized as emotional instability, immaturity, unsteadiness, lack of discipline, and rapid mood changes. We aimed to verify a possible correlation between structural brain abnormalities in magnetic resonance image (MRI) and the PD in JME using voxel-based morphometry (VBM). Sixteen JME patients with cluster B PD, 38 JME patients without psychiatric disorders, and 30 healthy controls were submitted to a psychiatric evaluation through SCID I and II and to a MRI scan. Significant reduction in thalami and increase in mesiofrontal and frontobasal regions volumes were observed mainly in JME patients with PD. Structural alterations of the orbitofrontal cortex (OFC), involved in regulation of mood reactivity, impulsivity, and social behavior, were also observed. This study supports the hypothesis of frontobasal involvement in the pathophysiology of cluster B PD related to JME.

Voxel-based morphometry evaluation of patients with photosensitive juvenile myoclonic epilepsy.

We aim to investigate structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients with photosensitivity (PS). Sixty JME patients, 19 (32%) of whom were photosensitive, were submitted to 1.5T magnetic resonance voxel-based morphometry (VBM). The control group (CTL) consisted of 30 sex-matched healthy volunteers. JME patients with (JME-PS) and without (JME-NPS) PS did not differ in their duration of disease, treatment or seizure control. VBM revealed significantly reduced bilateral gray matter volume (GMV) in thalami, insula cortices and cerebellar hemispheres; while significantly increased GMV was observed in the right superior frontal, orbitofrontal and medial frontal gyri of the JME group compared to CTL. JME-PS had reduced bilateral GMV of visual cortices when compared with CTL; while it was not seen among JME-NPS patients. Reduced left hippocampus and left inferior frontal gyrus volume was observed among JME-PS compared with JME-NPS. This study demonstrates structural abnormalities beyond the limits of the frontal lobes and provides evidence for the role of the occipital cortex in human PS, reinforcing the existence of functional-anatomic ictogenic networks in JME and the concept of system epilepsies.

Are personality traits of juvenile myoclonic epilepsy related to frontal lobe dysfunctions? A proton MRS study

Purpose:u2002 Personality traits characterized by emotional instability and immaturity, unsteadiness, lack of discipline, hedonism, frequent and rapid mood changes, and indifference toward one’s disease have been associated with patients who have juvenile myoclonic epilepsy (JME). Literature data demonstrate worse seizure control and more psychosocial dysfunctions among patients with JME who have those traits. In this controlled study we performed a correlation analysis of psychiatric scores with magnetic resonance spectroscopy (MRS) values across JME patients, aiming to verify the existence of a possible relation between frontal lobe dysfunction and the prevalence of personality disorders (PDs) in JME.

Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P<0.001), older age (P<0.001), and uncontrolled seizures (P=0.045). The intraclass coefficient (test-retest reliability) for LAEP overall score was 0.848 (95% CI=0.782-0.895), with a range from 0.370 (unsteadiness) to 0.750 (memory problems). Cronbachs α coefficient (internal consistency) was 0.903. The LAEP was highly correlated with Quality of Life in Epilepsy-31 inventory (r=-0.804, P>0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups.