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.

Epilepsy: Is there hope?

Epilepsy is a highly prevalent chronic neurologic disorder and leads to social, behavioural, health and economic consequences. 'Treatment gap' varies from 10 per cent in developed countries to 75 per cent in low-income countries. Stigma and discrimination related to epilepsy are prevalent worldwide. Electroencephalography (EEG) is considered the most important tool for evaluating the patient with epilepsy. Video-EEG monitoring is an important tool for confirming the seizure type and estimating the epileptogenic zone in the brain. Neuroimaging evaluation is important to determine the aetiology of the epilepsies. Genetic testing has increased the probability of identifying the causes of some types of epilepsies. Epilepsy can be treated in an affordable way with low-cost medications. Refractory epilepsies occur in approximately one-third of recently diagnosed patients with epilepsy. For this group of patients, there are options of surgical treatment, diets and neurostimulation to improve seizure control and quality of life. In poorly organized societies, there is a lack of prioritization of epilepsy in national health policies, limited resources for trained personnel and a shortage of basic antiepileptic medications. There is evidence of improvement in the understanding of epilepsy and a clear progress in the management of epileptic seizures in recent times.

Patterns of seizure control in patients with mesial temporal lobe epilepsy with and without hippocampus sclerosis.

OBJECTIVE: Patients with mesial temporal lobe epilepsy (MTLE) may present unstable pattern of seizures. We aimed to evaluate the occurrence of relapse-remitting seizures in MTLE with (MTLE-HS) and without (MTLE-NL) hippocampal sclerosis. METHOD: We evaluated 172 patients with MTLE-HS (122) or MTLE-NL (50). Relapse-remitting pattern was defined as periods longer than two years of seizure-freedom intercalated with seizure recurrence. "Infrequent seizures" was considered as up to three seizures per year and "frequent seizures" as any period of seizures higher than that. RESULTS: Thirty-seven (30%) MTLE-HS and 18 (36%) MTLE-NL patients had relapse-remitting pattern (X2, p = 0.470). This was more common in those with infrequent seizures (X2, p < 0.001). Twelve MTLE-HS and one MTLE-NL patients had prolonged seizure remission between the first and second decade of life (X2, p = 0.06). CONCLUSION: Similar proportion of MTLE-HS or MTLE-NL patients present relapse-remitting seizures and this occurs more often in those with infrequent seizures.

Patterns of seizure control in patients with mesial temporal lobe epilepsy with and without hippocampus sclerosis / Padrões de controle de crises em pacientes com epilepsia de lobo temporal com ou sem esclerose hipocampal

Objective Patients with mesial temporal lobe epilepsy (MTLE) may present unstable pattern of seizures. We aimed to evaluate the occurrence of relapse-remitting seizures in MTLE with (MTLE-HS) and without (MTLE-NL) hippocampal sclerosis. Method We evaluated 172 patients with MTLE-HS (122) or MTLE-NL (50). Relapse-remitting pattern was defined as periods longer than two years of seizure-freedom intercalated with seizure recurrence. “Infrequent seizures” was considered as up to three seizures per year and “frequent seizures” as any period of seizures higher than that. Results Thirty-seven (30%) MTLE-HS and 18 (36%) MTLE-NL patients had relapse-remitting pattern (X2, p = 0.470). This was more common in those with infrequent seizures (X2, p < 0.001). Twelve MTLE-HS and one MTLE-NL patients had prolonged seizure remission between the first and second decade of life (X2, p = 0.06). Conclusion Similar proportion of MTLE-HS or MTLE-NL patients present relapse-remitting seizures and this occurs more often in those with infrequent seizures. .

Objetivo Pacientes com epilepsia do lobo temporal mesial (ELTM) podem apresentar padrão instável de crises epilépticas. Nosso objetivo foi avaliar ocorrência de crises remitente-recorrentes em ELTM com (ELTM-EH) e sem (ELTM-NL) esclerose hipocampal. Método Avaliamos 172 pacientes com ELTM-EH (122) ou ELTM-NL (50). Padrão remitente-recorrente foi definido como períodos superiores a dois anos de remissão intercalados com recorrência de crises. Até três crises por ano foram consideradas como "infrequentes" e qualquer período com frequência maior como "frequentes". Resultados Trinta e sete (30%) pacientes com ELTM-EH e 18 (36%) com ELTM-NL apresentaram crises remitente-recorrentes (X2, p = 0,470), mais comum naqueles com crises infrequentes (X2, p < 0,001). Doze pacientes com ELTM-EH e um ELTM-NL apresentaram remissão prolongada de crises entre a primeira e a segunda década de vida (X2, p = 0,06). Conclusão Proporção semelhante de pacientes com ELTM-EH e ELTM-NL apresentam crises remitente-recorrentes e isso ocorre com maior frequência em pacientes com crises esporádicas. .

Comorbidities associated with epilepsy and headaches / Comorbidades associadas às epilepsias e cefaleias

Comorbidities are often associated with chronic neurological diseases, such as headache and epilepsy. OBJECTIVES: To identify comorbidities associated with epilepsy and headaches, and to determine possible drug interactions. METHODS: A standardized questionnaire with information about type of epilepsy/headache, medical history, and medication was administered to 80 adult subjects (40 with epilepsy and 40 with chronic headache). RESULTS: Patients with epilepsy had an average of two comorbidities and those with headache of three. For both groups, hypertension was the most prevalent. On average, patients with epilepsy were taking two antiepileptic medications and those with headache were taking only one prophylactic medication. Regarding concomitant medications, patients with epilepsy were in use, on average, of one drug and patients with headache of two. CONCLUSIONS: Patients with chronic neurological diseases, such as epilepsy and headaches, have a high number of comorbidities and they use many medications. This may contribute to poor adherence and interactions between different medications.

As comorbidades geralmente estão associadas a doenças neurológicas crônicas, tais como cefaleia e epilepsia. OBJETIVOS: Identificar comorbidades associadas à epilepsia e cefaleia e determinar as possíveis interações de drogas. MÉTODOS: Questionário padronizado com informações sobre o tipo de epilepsia/cefaleia, os antecedentes médicos e as medicações foi aplicado a 80 indivíduos adultos (40 com epilepsia e 40 com cefaleia crônica). RESULTADOS: Pacientes com epilepsia e cefaleia apresentaram uma média de duas e três comorbidades, respectivamente, sendo, para ambos, hipertensão arterial sistêmica a mais prevalente. Em média, os pacientes com epilepsia estavam em uso de duas medicações antiepilépticas; aqueles com cefaleia, uma medicação profilática. Em relação às medicações concomitantes, os pacientes com epilepsia estavam em uso, em média, de uma droga e os pacientes com cefaleia de duas. CONCLUSÕES: Pacientes com doenças neurológicas crônicas, como epilepsia e cefaleia, apresentam elevado número de comorbidades e utilizam grande número de medicações. Isso pode contribuir para diminuir a aderência ao tratamento e facilitar interações entre diversas medicações.

Comorbidities associated with epilepsy and headaches.

UNLABELLED: Comorbidities are often associated with chronic neurological diseases, such as headache and epilepsy. OBJECTIVES: To identify comorbidities associated with epilepsy and headaches, and to determine possible drug interactions. METHODS: A standardized questionnaire with information about type of epilepsy/headache, medical history, and medication was administered to 80 adult subjects (40 with epilepsy and 40 with chronic headache). RESULTS: Patients with epilepsy had an average of two comorbidities and those with headache of three. For both groups, hypertension was the most prevalent. On average, patients with epilepsy were taking two antiepileptic medications and those with headache were taking only one prophylactic medication. Regarding concomitant medications, patients with epilepsy were in use, on average, of one drug and patients with headache of two. CONCLUSIONS: Patients with chronic neurological diseases, such as epilepsy and headaches, have a high number of comorbidities and they use many medications. This may contribute to poor adherence and interactions between different medications.

Structural abnormalities of the thalamus in juvenile myoclonic epilepsy.

Studies have suggested that the thalamus is a key structure in the pathophysiology of juvenile myoclonic epilepsy. The objective of the present investigation was to examine the thalami of patients with juvenile myoclonic epilepsy using a combination of multiple structural neuroimaging modalities. The association between these techniques may reveal the mechanisms underlying juvenile myoclonic epilepsy and help to identify the neuroanatomical structures involved. Twenty-one patients with juvenile myoclonic epilepsy (13 women, mean age=30±9 years) and a control group of 20 healthy individuals (10 women, mean age=31±8 years) underwent MRI in a 2-T scanner. The volumetric three-dimensional sequence was used for structural investigation. Evaluation of the thalamus comprised voxel-based morphometry, automatic volumetry, and shape analysis. Comparisons were performed between patient and control groups. Voxel-based morphometry analysis identified areas of atrophy located in the anterior portion of the thalamus. Post hoc analysis of automatic volumetry did not reveal significant differences between the groups. Shape analysis disclosed differences between patients and controls in the anterior and inferior portions of the right thalamus and in the anterior portion of the left thalamus. The present investigation confirms that thalami of patients with juvenile myoclonic epilepsy are structurally abnormal with impairments located mainly in the anterior and inferior sections.

Modification in body weight associated with antiepileptic drugs.

UNLABELLED: Antiepileptic drugs (AED) may cause body weight changes. OBJECTIVE: To evaluate the dietary habits and body weight associated with AED in epileptic patients. METHOD: Sixty-six patients were subjected to two interviews, and had their weight and body mass index calculated and compared at both times, interval between six to eight months. RESULTS: It was observed that 59.1% showed weight gain. The patients who had no weight gain had a greater proportion of individuals who engaged in some form of physical activity. However, of the 45 patients who maintained their initial dietary and medication pattern, 75.6% recorded a weight gain. Weight gain was seen in 66.7% of patients on carbamazepine (n=18), 60% on valproate (n=5), 50% on carbamazepine+clobazam treatment (n=14), and 58.3% of patients on other(s) polytherapy (n=12). CONCLUSION: The patient should be alerted to possible weight gain, and should be advised about dieting and participating in regular physical activity.

Modification in body weight associated with antiepileptic drugs / Alteração de peso corpóreo associado às drogas antiepilépticas

Antiepileptic drugs (AED) may cause body weight changes. OBJECTIVE: To evaluate the dietary habits and body weight associated with AED in epileptic patients. METHOD: Sixty-six patients were subjected to two interviews, and had their weight and body mass index calculated and compared at both times, interval between six to eight months. RESULTS: It was observed that 59.1 percent showed weight gain. The patients who had no weight gain had a greater proportion of individuals who engaged in some form of physical activity. However, of the 45 patients who maintained their initial dietary and medication pattern, 75.6 percent recorded a weight gain. Weight gain was seen in 66.7 percent of patients on carbamazepine (n=18), 60 percent on valproate (n=5), 50 percent on carbamazepine+clobazam treatment (n=14), and 58.3 percent of patients on other(s) polytherapy (n=12). CONCLUSION: The patient should be alerted to possible weight gain, and should be advised about dieting and participating in regular physical activity.

Drogas antiepilépticas (DAE) podem causar alteração do peso corpóreo. OBJETIVO: Avaliar o hábito alimentar e do peso corpóreo associado às DAE em pacientes epilépticos. MÉTODO: Sessenta e seis pacientes foram submetidos a duas entrevistas, e tiveram peso e índice de massa corpórea (IMC) calculados e comparados nos dois momentos, com intervalo de 6 a 8 meses. RESULTADOS: Apresentaram aumento de peso 59,1 por cento dos pacientes. Porém, os pacientes que não tiveram ganho de peso apresentaram maior proporção de indivíduos desenvolvendo alguma atividade física. Enquanto que dentre os 45 que mantiveram o padrão alimentar e medicação inicial 75,6 por cento registraram ganho de peso. Observou-se ganho de peso em 66,7 por cento dos pacientes com carbamazepina (n=18); 60 por cento com valproato (n=5); 50 por cento com carbamazepina e clobazam (n=14); 58,3 por cento dos pacientes com politerapia (n=12). CONCLUSÃO: Deve-se alertar o paciente sobre o ganho de peso, orientar quanto à dieta alimentar e, principalmente, incentivar atividade física regular.

Correlation between quantitative EEG and MRI in idiopathic generalized epilepsy.

The objective of this study was to investigate the relationship between the focal discharges sometimes observed in the electroencephalogram of patients with idiopathic generalized epilepsies and subtle structural magnetic resonance imaging abnormalities. The main hypothesis to be assessed is that focal discharges may arise from areas of structural abnormality which can be detected by quantitative neuroimaging. Focal discharges were used for quantitative electroencephalogram source detection. Neuroimaging investigations consisted of voxel-based morphometry and region of interest volumetry. For voxel-based morphometry, volumetric MRI were acquired and processed. The images of each patient were individually compared with a control group. Statistical analysis was used to detect differences in gray matter volumes. Region of interest-based morphometry was automatically performed and used essentially to confirm voxel-based morphometry findings. The localization of the focal discharges on the electroencephalogram was compared to the neuroimaging results. Twenty-two patients with idiopathic generalized epilepsies were evaluated. Gray matter abnormalities were detected by voxel-based morphometry analysis in 77% of the patients. There was a good concordance between EEG source detection and voxel-based morphometry. On average, the nearest voxels detected by these methods were 19 mm (mm) apart and the most statistically significant voxels were 34 mm apart. This study suggests that in some cases subtle gray matter abnormalities are associated with focal epileptiform discharges observed in the electroencephalograms of patients with idiopathic generalized epilepsies.

Focal electrical status (FES): a new finding associated with polymicrogyria.

Polymicrogyria (PMG), a malformation of cortical organization, may, occasionally, be associated with electrical status epilepticus of sleep and focal electrical status. The aim of this study was to better characterize the latter association. This was an historic cohort study. Inclusion criteria were diagnosis of PMG on neuroimaging and presence of focal electrical status on EEG. Focal electrical status was considered when patients presented with continuous epileptiform abnormalities over a focal area on awakeness, which became bilateral and synchronous during sleep. Interictal EEGs lasted for at least 20 minutes and up to 4 hours and were performed during awakeness and sleep. Neuroimaging findings were classified as holosylvian PMG and hemispheric PMG. All patients, except one, had asymmetric neuroimaging findings, mostly on the right side. All patients had partial motor seizures, which were easily controlled with antiepileptic drugs in two of them. Despite seizure control, their EEGs still registered focal electrical status. The other four patients presented with atonic seizures and/or atypical absences. All patients showed awakeness focal electrical status that was activated by sleep. Focal electrical status is a different EEG pattern from other continuous electrographical patterns previously described, such as electrical status epilepticus of sleep, continuous epileptiform discharges, and rhythmic epileptiform discharges. Each one has its own peculiarity. Focal electrical status seems to be associated with asymmetric and extensive PMG.

Cuidados na interpretação dos guias para tratamento medicamentoso de epilepsia / Caution in the interpretation of guidelines for drug treatment of epilepsy

Este artigo revê de modo crítico o papel da medicina baseada em evidência, os guias desde sua preparação até a sua interpretação. Os pontos fortes e suas limitações são apresentados e o porquê da sua extrema popularidade, principalmente nos países desenvolvidos. Discute aspectos importantes destes guias para o tratamento medicamentoso das epilepsias, assim como alguns recentes ensaios clínicos sobre o uso de novas drogas antiepilépticas. Conclui ainda que mesmo quando há evidências a experiência clínica não deve ser substituída ou negligenciada, uma vez que a conduta final deve ser tomada pelo clínico diante do seu paciente específico com suas necessidades especiais.

This article critically reviews the role of evidence-based medicine and its guidelines, from their logistic preparation to their interpretation. The strengths and weaknesses of the methodological points are presented, as well the reasons for the extreme popularity of the guidelines in developed countries. The review discusses the main foundations of the most cited guidelines and some recent large studies. Some of the final conclusions are that clinical experience is always an important factor to consider, even in the face of solid evidence, to achieve the best possible management of any particular patient.

Tratamento das epilepsias generalizadas idiopáticas / Idiopathic generalized epilepsies treatment

As epilepsias generalizadas idiopáticas (EGIs) correspondem a um-terço de todas as epilepsias. Apesar desta elevada freqüência, as EGIs permanecem pouco reconhecidas. As características clínicas são fundamentais para o diagnóstico. Neste grupo de epilepsias, todos os tipos de crises generalizadas podem ocorrer especialmente as crises tônico-clônicas generalizadas, as crises mioclônicas e as crises de ausência. O eletroencefograma é bastante sugestivo do diagnóstico quando evidencia os típicos complexos espículas ou poliespículas-onda lenta, generalizados, simétricos e com atividade de base normal. De acordo com o tipo de crise predominante e com a idade de início das crises, as EGIs são divididas em subsíndromes. A importância do diagnóstico preciso está relacionada com a elevada porcentagem de indivíduos livre de crises quando tratados com a medicação antiepiléptica apropriada. Por outro lado, o uso de algumas medicações antiepilépticas como carbamazepina e fenitoína pode exacerbar as crises ou até mesmo induzir estado de mal epiléptico em determinadas subsíndromes. Neste artigo, revisamos as principais medicações antiepilépticas utilizadas no tratamento das EGIs bem como alguns aspectos práticos no tratamento das subsíndromes mais freqüentes.

Idiopathic generalized epilepsies (IGEs) correspond to one-third of all epilepsies. Despite of this high frequency, IGEs remains underdiagnosed. Clinical features are the cornerstone to diagnosis. In this group all types of generalized seizures may occur such as generalized tonic-clonic, absences and myoclonic seizures. EEG is very supportive of IGEs diagnosis when it shows the typical generalized symmetrical, spike or polispyke and waves complexes with normal background. According to the main seizure type and the age of onset, IGEs are divided in subsyndromes. The importance of the correct diagnosis is supported by the high rate of seizure free patients under appropriate antiepileptic drug therapy. On the other hand, the use of some antiepileptic drugs such as carbamazepine or phenytoin may exacerbate the seizures or even induce status epilepticus in some subsyndromes. In this article, the main antiepileptic drugs used in the treatment of IGEs are reviewed as well as some practical issues for IGEs subsyndromes treatment.

Tratamento das epilepsias parciais / Partial epilepsies treatment

As epilepsias parciais constituem a forma mais comum de epilepsia nos indivíduos adultos. As drogas antiepilépticas (DAEs) permanecem como a principal forma de tratamento para os pacientes com epilepsia. Apesar da importância da medicação um número elevado de pacientes permanece sob um regime terapêutico inapropriado ou até mesmo sem qualquer medicação. Existem várias medicações disponíveis para o tratamento das epilepsias. A escolha de uma medicação específica ou a associação entre DAEs deve ser particularizada o máximo possível. Neste artigo revisamos alguns aspectos como classificação, início das crises, idade, sexo, comorbidades, custo e posologia das DAEs e história medicamentosa com a perspectiva de auxiliar nesta individualização do tratamento. Algumas características das principais DAEs disponíveis também são discutidas. Estes aspectos podem auxiliar na criação de um perfil ajudando assim na escolha do regime terapêutico mais apropriado para cada indivíduo. Aspectos práticos como o manuseio dos efeitos adversos, monoterapia e politerapia também são abordados.

Partial epilepsies are the most common form of epilepsy in adult individuals. Antiepileptic drugs (AEDs) continue as the main form of treatment for patients with epilepsy. Regardless of the importance of the medication a high number of patients are under inappropriate or not receiving AEDs. There are several medications available for the treatment of epilepsy. The choice of a particular medication or association among AEDs may be individualized as much as possible. In this article some aspects such as classification, onset of the seizures, age, sex, associated medical conditions, cost and posology of AEDs and medical drug history are reviewed. Details of the available AEDs are also discussed. These points may help to create a profile helping the decision for the appropriate AED. Some practical issues like adverse reaction management, monotherapy and politherapy are also discussed.

Guidelines for drug treatment of epilepsy: a critical review.

This article critically reviews the role of evidence-based medicine and its guidelines, from their logistic preparation to their interpretation. The strengths and weaknesses of the methodological points are presented, as well the reasons for the extreme popularity of the guidelines in developed countries. The review discusses the main foundations of the most cited guidelines and some recent large studies. Some of the final conclusions are that clinical experience is always an important factor to consider, even in the face of solid evidence, to achieve the best possible management of any particular patient.

Guidelines for drug treatment of epilepsy: a critical review / Guias para tratamento medicamentoso de epilepsia: uma revisão crítica

This article critically reviews the role of evidence-based medicine and its guidelines, from their logistic preparation to their interpretation. The strengths and weaknesses of the methodological points are presented, as well the reasons for the extreme popularity of the guidelines in developed countries. The review discusses the main foundations of the most cited guidelines and some recent large studies. Some of the final conclusions are that clinical experience is always an important factor to consider, even in the face of solid evidence, to achieve the best possible management of any particular patient.

Este artigo revê de modo crítico o papel da medicina baseada em evidência e alguns dos guias mais citados, desde a logística de preparação até a interpretação. Os pontos fortes e as limitações são apresentados, assim como o porquê da extrema popularidade, especialmente nos países desenvolvidos. São discutidos aspectos importantes e os principais achados, assim como recentes ensaios clínicos sobre o uso de novas drogas antiepilépticas. O artigo conclui que mesmo quando há evidência apoiando certa escolha, a experiência clínica não deve ser substituída ou negligenciada, uma vez que a conduta final deve ser tomada pelo clínico diante do seu paciente considerando as suas necessidades especiais.