La epilepsia mioclónica juvenil y las disfunciones neurocognitivas y ejecutivas asociadas / Juvenile myoclonic epilepsy and associated neurocognitive and executive dysfunctions

Resumen La epilepsia mioclónica juvenil (EMJ) es un trastorno benigno con buena respuesta a la medicación antiepiléptica. Evaluaciones neuropsicológicas revelaron trastornos cognitivos leves. El objetivo de este estudio es determinar el desempeño cognitivo y síntomas anímicos de la EMJ comparados con controles normales. Se evaluaron en forma prospectiva 30 pacientes con EMJ y 29 controles pareados por edad, género, y escolaridad. Se analizaron las características clínicas de la EMJ. Se administró una batería cognitiva completa, un cuestionario auto-administrado de dificultades ejecutivas (DEX), un inventario de depresión validado para epilepsia NDDI-E, escala de depresión de Beck (BDI), escala de ansiedad (GAD-7) y escala de riesgo de suicidio (MINI). Sin diferencias significativas en edad y escolaridad ent re EMJ y controles. Tiempo medio de evolución de la enfermedad, 18 años. El 53% presentó tres tipos de crisis, mioclonías, ausencias y convulsiones tónico-clónicas generalizadas. Hubo diferencias significativas con mayores fallas en atención, funciones ejecutivas, un puntaje significativamente mayor en el DEX en pacientes con EMJ. Se encontró un mayor puntaje en el NDDI-E, BDI y GAD-7 en EMJ. No se hallaron diferencias en el riesgo de suicidio respecto a controles. El estudio confirma que la EMJ presenta mayores fallas en el funcionamiento atencional y las habilidades ejecutivas relacionadas con la flexibilidad e inhibición, siendo en la mayoría de los casos los pacientes conscientes de sus dificultades. Conocer estas dificultades permitirá un mejor abordaje terapéutico, y mejorar síntomas muchas veces desestimados.

Abstract Juvenile myoclonic epilepsy (JME) is a benign disorder with a good response to antiepileptic drugs. Neurop sychological evaluations revealed mild cognitive deficits. The objective of this study is to determine the cognitive profile and mood symptoms in JME compared to normal controls. 30 patients with JME and 29 controls matched for age, gender, and education level were prospectively evaluated. The clinical characteristics were analysed. They were given a complete cognitive battery, a self-administered questionnaire of executive difficulties (DEX), the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Beck Depression Inventory (BDI), Generalized Anxiety Disorder Scale (GAD-7) and suicide risk scale (MINI). No significant differences in age and education were observed between JME and controls. Average time of evolution of the disease 18 years, 53% have three types of seizures: myoclonic, absence seizures and tonic-clonic seizures. Significant differences were found with greater failures in attention, executive function, a significantly higher score values in DEX in JME subjects. A higher score was found in the NDDI-E; BDI and GAD-7. No differences were found in the risk of suicide with respect to controls. The study confirms that JME presents greater failures in attentional functioning and executive skills related to flexibility and inhibition, with patients being aware of their difficulties in most cases. Knowing these difficulties would allow a better therapeutic approach to improve symptoms usually dismissed.

Research progress on transient receptor potential melastatin 2 channel in nervous system diseases / 浙江大学学报·医学版

Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer's disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.

Cognition of Patients with Juvenile Myclonic Epilepsy / 中国康复理论与实践

Objective To investigate the cognitive function and psychological mental state of patients with juvenile myoclonic epilepsy (JME), and the related risk factors. Methods From September, 2011 to Febrary, 2014, 21 patients with JME and 18 healthy controls matched with age, sex and educational level were assessed with Montreal Cognitive Assessment (MoCA), and Revised Chinese Wechsler Adult Intel-ligence Scale (WAIS-RC) and Symptom Checklist-90 (SCL-90). The risk factors were analyzed with Logistic regression analysis. Results There was no significant difference in the score of MoCA between two groups (t=―1.544, P=0.131). The scores of verbal intelligence quo-tient (VIQ), performance intelligence quotient (PIQ) and full intelligence quotient (FIQ) in WAIS-RC were significantly lower in the patient group than in the control group (t>4.119, P2.480, P<0.05). Logis-tic regression analysis showed that VIQ significantly decreased in patients taking valproic acid (B=―3.064, OR=0.047, 95% CI=0.002~0.920, P=0.044). Conclusion VIQ, PIQ and FIQ decreased in patients with JME. Furthermore, different levels of dysfunction were found in interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism. Taking valproic acid was the risk factor of cognitive decline.

The characteristical and clinical value of Somatosensory Evoked Potential and event?related potential P300 in Patients With Juvenile Myoclonic Epilepsy / 实用医学杂志

Objective To explore the characteristic and clinical value of Somatosensory Evoked Potential SEP and event?related potential P300 in patients with Juvenile Myoclonic Epilepsy (JME), trying to provide neuroelectrophysiological evidence for the pathogenesis, diagnosis and antiepileptic drug efficacy of this disease . Methods 28 patients with JME and 30 healthy controls were enrolled in the research. They were applied the SEP and P300 before and after one year treatment. Results (1) The amplitude of SEP in patients with JME was significantly higher than those in the control group(P=0.000), the abnormal rate was 75%(21/28), while the latency of SEP was no significant difference (P>0.05); The latency of P300 in patients with JME was significantly longer (P = 0.000), 2 out of 28 cases were poorly differentiated, 9 cases were longer (11/28, 39%), while the P300 amplitude was no significant difference(P=0.110). (2) After treatment, the amplitude of SEP was significantly lower (P<0.05), the latency of P300 was significantly shorter (P=0.001). (3) The amplitude of SEP had a positively linear relationship with the latency of P300 (r = 0.818, P = 0.000). Conclusions The SEP amplitude was significantly higher in patients with JME, often accompanied by a huge SEP, so SEP can provide electrophysiological evidence for the pathogenesis and diagnosis of this disease.And P300 may give a chance to find the subclinical cognitive abnormalities and to intervent it early. The SEP had a positively linear relationship with the P300, simultaneously dynamic monitoring the change of SEP amplitude and P300 latency may become an objective evaluation for the antiepileptic drug efficacy.

Lack of association between the prothrombin rs1799963 polymorphism and juvenile myoclonic epilepsy / Ausência de associação entre o polimorfismo G20210A (rs1799963) da protrombina e epilepsia mioclônica juvenil

Juvenile myoclonic epilepsy (JME) accounts for 26% of generalized idiopathic epileptic syndromes. The highest levels of thrombin activity are closely involved in the development of neurological diseases, including epilepsy. The prothrombin c.20210G>A (rs1799963) variation, which alters prothrombin mRNA stability, is associated with high plasma prothrombin levels. Objective : The present study was designed to investigate whether the SNP rs1799963 is a risk factor for JME in the northeastern Brazilian population. Results : The polymorphism was genotyped in 207 controls and 123 patients using polymerase chain reaction-restriction fragment length polymorphism method. No significant differences were observed in the genotype and allele frequencies of this polymorphism between cases and controls. Conclusion : These results present no evidence for an association of rs1799963 with JME. Further studies including other types of epilepsy are required to investigate the involvement of prothrombin gene in the genetic susceptibility to chronic seizure. .

Epilepsia mioclônica juvenil (EMJ) representa 26% das síndromes epilépticas idiopáticas generalizadas. Níveis elevados de atividade da trombina estão intimamente envolvidos no desenvolvimento de distúrbios neurológicos, incluindo epilepsia. A variante c.20210G>A (rs1799963) do gene de protrombina, que altera a estabilidade do RNAm, está associada com altos níveis de protrombina no plasma. Objetivo: Investigar se o SNP rs1799963 é um fator de risco para EMJ em uma amostra da população do nordeste brasileiro. Resultados : O polimorfismo foi genotipado em 123 pacientes e 207 controles usando a reação de polimerase em cadeia com restrição de polimorfismo. Não observamos diferença significativa nas frequências alélicas e genotípicas deste polimorfismo, entre as populações de pacientes e controle. Conclusão : Estes resultados não demonstram evidências para uma associação do polimorfismo rs1799963 com EMJ. Estudos posteriores, incluindo outros tipos de epilepsia, são necessários para investigar o envolvimento do gene protrombina na susceptibilidade genética a crises crônicas. .

Circadian rhythm and profile in patients with juvenile myoclonic epilepsy and temporal lobe epilepsy / Ritmo e perfil circadiano em pacientes com epilepsia mioclônica juvenil e epilepsia de lobo temporal

Objective This study intended to compare the circadian rhythm and circadian profile between patients with juvenile myoclonic epilepsy (JME) and patients with temporal lobe epilepsy (TLE). Method We enrolled 16 patients with JME and 37 patients with TLE from the Outpatient Clinic of UNICAMP. We applied a questionnaire about sleep-wake cycle and circadian profile. Results Fourteen (87%) out of 16 patients with JME, and 22 out of 37 (59%) patients with TLE reported that they would sleep after seizure (p < 0.05). Three (19%) patients with JME, and 17 (46%) reported to be in better state before 10:00 AM (p < 0.05). Conclusion There is no clear distinct profile and circadian pattern in patients with JME in comparison to TLE patients. However, our data suggest that most JME patients do not feel in better shape early in the day. .

Objetivo Este estudo pretende comparar o ritmo circadiano e o perfil circadiano entre pacientes com epilepsia mioclônica juvenil (EMJ) e epilepsia de lobo temporal (ELT). Método Nós entrevistamos 16 pacientes com EMJ e 37 com ELT do ambulatório da UNICAMP. Nós aplicamos um questionário sobre ciclo sono-vigília e perfil circadiano. Resultados Quatorze (87%) de 16 pacientes com EMJ e 22 de 37 (59%) pacientes com ELT relataram que eles apresentam sonolência pós-crise (p < 0,05). Três (19%) pacientes com EMJ e 17 (46%) relataram um melhor estado geral antes das 10h00min (p < 0,05). Conclusão Não há uma clara diferença de ritmo e de perfil circadiano entre pacientes com EMJ e ELT. No entanto, nossos dados sugerem que a maioria dos pacientes com EMJ não se sentem em sua melhor forma cedo pela manhã. .

A unique case of Ito syndrome presenting with Juvenile Myoclonic Epilepsy and normal intelligence

Background: Hypomelanosis of Ito is a neurocutaineous disease commonly associated with seizure and mental retardation. Case description: In this case report, we have found a unique coexistence of Hypomelanosis of Ito and Juvenile Myoclonic Epilepsy with normal intelligence. Discussion: The occurances of two genetically linked disease entities in a single individual arouse a possibility of some common genetic factors. Conclusion: The Juvenile myoclonic Epilepsy with normal intelligence can be a presenting feature in Hypomelanosis of ito. Key message: In contrary to common perception Hypomelanosis of ito can present with normal intelligence and the seizure type can be Juvenile myoclonic epilepsy as found in this case

Efficacy and Tolerability of Valproic Acid Once Daily Dosing for Juvenile Myoclonic Epilepsy / 대한소아신경학회지

PURPOSE: The purpose of this study was to evaluate the efficacy and tolerability of extended-release valproic acid once daily dosing in juvenile myoclonic epilepsy (JME). METHODS: Medical records of patients who received valproic acid monotherapy for the treatment of JME were retrospectively reviewed. Their clinical information regarding age, gender, seizure types, underlying neurologic status, dosing regimen, response to treatment, and adverse events related to valproic acid, were analyzed. Seizure control, compliance, and adverse events rates were compared between the group of once daily dosing and the group of twice daily dosing. RESULTS: Twenty one patients (11 boys and 10 girls) were included in the study. Twelve patients were taking valproic acid extended-release once daily and nine patients were taking twice a day. More than 50% decrease in myoclonic seizure was achieved in all the patients in both groups. Generalized tonic-clonic seizure was controlled in all the patients who were taking once daily while 3 patients (36%, 3/8 patients) in twice daily group had breakthrough generalized tonic clonic seizures during the 2 year period of treatment. However, there were no statistically significant differences in seizure control, compliance, and adverse event rates between the two groups. CONCLUSION: This study demonstrated that valproic acid extended-release once daily dosing was as effective and tolerable as twice daily in the treatment of JME. Once daily dosing of valproic acid would be convenient which improve patient compliance and consequently bring better outcome in treatment of JME.

Epilepsia mioclônica juvenil / Juvenile myoclonic epilepsy

A epilepsia mioclônica juvenil (EMJ) foi descrita por Janz e Christian em 1957, sendo inicialmente denominada "pequeno mal impulsivo". Atualmente é considerada a mais frequente das epilepsias generalizadas idiopáticas e é caracterizada, clinicamente, por três tipos distintos de crises epiléticas: crises mioclônicas, crises tônico-clônicas generalizadas e ausências. Corresponde a uma síndrome epilética idade-relacionada, com pico entre 12 e 14 anos, comprometendo ambos os sexos de forma semelhante. É uma síndrome geneticamente heterogênea e relacionada a mutações em diversos genes, como o GABRA1 (cromossomo 5q34-q35), o CACNB4 (cromossomo 2q22-q23), o CLCN2 (cromossomo 3q26) e o EFHC1 (cromossomo 6p12-p11). Os achados eletroencefalográficos também são heterogêneos, sendo observadas descargas de espícula, polispícula, espícula-onda ou polispícula-onda em projeção generalizada. Há diversos relatos de descargas focais no EEG destes pacientes. A fisiopatogenia da EMJ permanece não totalmente esclarecida, embora mutações nos canais de cloro, disfunções talâmicas e alterações nos receptores de serotonina estejam provavelmente implicadas. Evitar fatores desencadeantes, como privação de sono, uso abusivo de álcool e/ou café, estresse físico/emocional são parte fundamental do tratamento. O valproato de sódio é a droga de primeira linha no tratamento da EMJ, embora outras drogas antiepiléticas, como o clonazepam e a lamotrigina, já se tenham mostrado eficazes. Topiramato e zonisamide são consideradas promissoras no tratamento da EMJ, enquanto carbamazepina, oxcarbazepina, fenitoína, vigabatrina e gabapentina são contraindicadas...

Epilepsia Mioclônica Juvenil: endofenótipos distintos considerando aspectos neuropsicológicos, traços de personalidade e variáveis clínicas / Juvenile Myoclonic Epilepsy: distinct phenotypes considering aspects neuropsychological, personality traits and variables clinics

INTRODUÇÃO: Estudos neuropsicológicos sugerem que indivíduos com EMJ apresentam disfunção executiva além de maior impulsividade, refletindo uma disfunção de lobo frontal. Este estudo teve como objetivos verificar: 1. o desempenho e gravidade de comprometimento das funções executivas; 2. presença de traços de personalidade impulsivos; 3. a correlação entre o desempenho nas funções cognitivas e a expressão de traços de personalidade impulsivos e; 4. se as variáveis da epilepsia se correlacionam com as disfunções executivas e a um pior controle de impulsos. MÉTODOS: Foram avaliados 42 pacientes com EMJ e 42 sujeitos saudáveis pareados por idade, escolaridade e nível socioeconômico, através de bateria compreensiva de testes neuropsicológicos avaliadores de funções executivas e questionário padronizado de avaliação de traços de personalidade (ITC). RESULTADOS: Pacientes com EMJ tiveram pior desempenho nos testes de atenção imediata, seletiva e sustentada; controle mental e inibitório; flexibilidade mental; fluência verbal; formação de conceitos e manutenção de metas. A disfunção executiva foi moderada/grave em 83,33 por cento. Pacientes com EMJ apresentaram maior expressão dos traços de personalidade impulsivos. A disfunção executiva se correlacionou com o pior controle dos impulsos. Pacientes refratários apresentaram pior disfunção executiva e maior expressão de traços impulsivos. CONCLUSÕES: Nosso estudo demonstra a presença de disfunção atencional e executiva nos pacientes com EMJ, além da presença de traços de personalidade impulsivos. Além disso, verificamos a existência de dois grupos distintos de pacientes, sendo que pacientes mais refratários apresentam-se globalmente comprometidos. Estes achados sugerem que há uma necessidade de melhor caracterização fenotípica dos pacientes com EMJ a fim de incluir endofenótipos visto que nossos resultados demonstram uma possível existência de grupos distintos de pacientes com EMJ.

INTRODUCTION: Neuropsychological studies suggest that patients with JME have executive dysfunction and impulsiveness, reflecting a possible frontal lobe dysfunction. This study aimed to verify: 1. the performance and severity of attentional and executive functions; 2. presence of impulsive personality traits; 3. correlation between cognitive performance and the expressions of impulsive personality traits; 4. correlation between epilepsy variables and neuropsychological performance as well as worse impulse control. METHODS: We evaluated 42 patients with JME and a group of 42 control subjects, matched for age, education and socioeconomic status with a comprehensive battery of neuropsychological tests of attentional and executive functions and a standardized assessment of personality traits (TCI). RESULTS: Patients with JME showed worse performance than controls on tests of attentional span, working memory, inhibitory control, concept formation, maintenance of goals, and verbal fluency. Executive dysfunction was severe/moderate in 83.33 percent. Patients with JME showed higher expression of personality traits associated with an impaired impulse control. Attentional/executive dysfunction was correlated with poor impulse control. Refractory patients had worse executive dysfunction with an even a greater presence of impulsive personality traits. CONCLUSIONS: Our study demonstrates the presence of attentional and executive dysfunction in patients with JME, as well as the presence of impulsive personality traits. We also note the existence of two distinct groups of patients, were more refractory patients appear to present broader impairment. These findings suggest that there is a need for better phenotypic characterization of patients with JME to include diverse phenotypes since our results suggest a possible existence of distinct groups of patients with JME.

Adherence to treatment in patients with juvenile myoclonic epilepsy: correlation with quality of life and adverse effects of medication / Adesão ao tratamento em pacientes com Epilepsia Mioclônica Juvenil: correlação com qualidade de vida e efeitos adversos da medicação

PURPOSE: To study the adherence to clinical treatment in patients with Juvenile Myoclonic Epilepsy (JME) and its correlation to Quality of Life (QOL) scores, and antiepileptic drugs (AEDs) adverse effects. METHODS: Forty-three JME (ILAE,1989) outpatients in regular treatment were evaluated by clinical anamnesis and EEG/video-EEG at Hospital São Paulo, UNIFESP, Brazil. They answered a self-report questionnaire assessing adherence to treatment (scores 0 to 100), with higher scores meaning poorer adherence; Quality of Life in Epilepsy-31 (QOLIE-31) Brazilian validated version (scores 0 to 100), and the Adverse Events Profile (AEP), scores 19 to 76, in which scores ≥45 indicate toxicity; values less than 0.05 were considered statistically significant. RESULTS: Sixteen patients (37,2 percent) were on monotherapy, while 26 (60.4 percent) on polytherapy. Twenty-two (48 percent) had experienced a seizure in the preceding three months of the survey. Mean adherence to treatment score was 68.5. AEP scores ≤45 were observed in 38 (88.3 percent), and 29 (67.4 percent) reported spontaneous adverse effects with AEDs. The most common adverse effects were sleepiness in 11(13.8 percent), and restlessness in 7(8.8 percent).QOLIE-31 highest mean score was 79.0 (Social Function), and the lowest 33.0 (Seizure Worry). Adherence to treatment presented good correlation to better QOL scores (Pearson<0.05), while higher AEP scores indicated poorer adherence (Pearson<0.05). CONCLUSIONS: Adherence to treatment showed high correlation to better QOL. The presence of adverse effects was negatively associated with adherence.

OBJETIVOS: Este estudo teve como objetivo avaliar a adesão ao tratamento com drogas antiepilépticas (DAEs) em pacientes com Epilepsia Mioclônica Juvenil (EMJ) e correlacionar com a Qualidade de Vida (QV) e com os efeitos adversos à medicação. METODOLOGIA: A amostra foi composta de 43 pacientes com diagnóstico clínico e eletrográfico (EEG/Vídeo-EEG) de EMJ (ILAE,1989), em tratamento regular no Hospital São Paulo, UNIFESP, Brasil. Todos os pacientes responderam a um questionário de adesão ao tratamento (escores de 0-100), em que escores mais elevados evidenciavam uma pobre adesão ao tratamento. Para avaliar a QV foi utilizada a versão brasileira validada do Quality of Life in Epilepsy Inventory 31 (QOLIE-31); os efeitos adversos das DAEs foram avaliados através do Adverse Events Profile (AEP), escores de 19 a 76, no qual escores ≥45 indicam toxicidade. Foram considerados significantes os valores de p<0,05. RESULTADOS: Dezesseis pacientes (37,2 por cento) estavam em monoterapia e 26 (60,4 por cento), em politerapia; 22 (48 por cento) tiveram uma crise nos últimos três meses antes da entrevista. A média de adesão ao tratamento foi 68.5. Foram observados escores ≤45 em 38 (88.3 por cento) no AEP e 29 (67.4 por cento) apresentaram queixas espontâneas em relação ao uso das DAEs. Os efeitos adversos mais comuns foram sonolência em 11 (13,8 por cento) e inquietação em 7 (8,8 por cento). A maior média do QOLIE-31 foi 79,0 (Funcionamento Social), e a mais baixa 33,0 (Preocupação com as Crises). A adesão ao tratamento apresentou correlação estatística com valores melhores na QV enquanto valores elevados no AEP indicaram pior adesão (Pearson <0,05). CONCLUSÃO: A adesão ao tratamento mostrou alta correlação com uma melhor QV. A presença de efeitos adversos foi negativamente associada com a adesão ao tratamento.

Epilepsia mioclônica juvenil: estudo clínico, epidemiológico, terapêutico e da qualidade de vida / Juvenile myoclonic epilepsy: a clinical, epidemiological, therapeutic and quality of life study

INTRODUÇÃO: A Epilepsia Mioclônica Juvenil (EMJ) é uma epilepsia idiopática generalizada, que, apesar de descrita há mais de um século, é uma entidade clínica ainda subdiagnosticada. OBJETIVO: Apresentar o perfil clínico, epidemiológico e terapêutico de pacientes com EMJ, além de mensurar a qualidade de vida destes. METODOLOGIA: Foram avaliados dezenove pacientes com EMJ, acompanhados no Hospital Universitário da Universidade Federal de Alagoas, com o Protocolo de Consulta Clínica e o QOLIE-31 (Quality of life in epilepsy), versão brasileira. RESULTADOS: O estudo mostrou que dentre os 19 pacientes selecionados, 12 (63 por cento) eram do sexo feminino; a idade de início das crises epiléticas teve média de 12 anos (±3); a história familiar para epilepsia foi positiva 78,9 por cento dos entrevistados; todos apresentavam crises mioclônicas de predomínio matinal associadas a crises tônico-clônicas generalizadas; 14 pacientes (73,7 por cento) estavam em monoterapia, sendo 13 com o ácido valpróico. A "Pontuação Global" (Overall score) do QOLIE-31 variou de 26 a 98, com média de 62,1 (±18,4) e T-score (escore padronizado) corresponde a 47. CONCLUSÃO: A análise dos resultados auxilia sobremaneira na melhor caracterização deste grupo de pacientes, além de quantificar através de instrumento validado, pela primeira vez, a qualidade de vida destes, a qual não pode mais ser ignorada no seu manejo.

INTRODUCTION: The Juvenile Myoclonic Epilepsy (JME) is an idiopathic generalized epilepsy that, despite being descripted for more than a century, it is still a clinical entity often misdiagnosed. OBJECTIVE: Introduce the clinical, epidemiological and therapeutic profile of patients with JME, addition to measuring the quality of their life. METHODOLOGY: Nineteen patients carrying JME were evaluated. They had been examinated at the Federal University of Alagoas' Academic Hospital, with the Clinical Enquiry Protocol and the QOLIE-31 (Quality of life in epilepsy), Brasilian version. RESULTS: Among the 19 selected patients, 63 percent were female; the average age for the first seizure was twelve years (±3); the epilepsy familiar history were positive in 78,9 percent of the patients; all patients presented myoclonic seizures with matinal predominance associated to generalized tonic-clonic seizures; 14 patients (73,7 percent) were in monotherapy, 13 of these with sodium valproate. The "Overall score" of QOLIE-31 range from 26 to 98, with an average score of 62,1 (±18,4) and T-score (standardized score) corresponding 47. CONCLUSION: The analysis helps considerably in the best characterization of this group of patients and quantifies for the first time, through validated instrument, the quality of life of them, which can no longer be ignored in their management.

Espectroscopia por ressonância magnética de prótons em epilepsia mioclônica juvenil sugere o comprometimento de uma rede neuronal específica / Proton magnetic resonance spectroscopy study of juvenile myoclonic epilepsy patients suggests involvement of a specific neuronal network

OBJECTIVES: The neuroanatomical basis and the neurochemical abnormalities that underlay juvenile myoclonic epilepsy (JME) are not fully defined. While the thalamus plays a central role in synchronization of widespread regions of the cerebral cortex during a seizure, emerging evidence suggests that all cortical neurons may not be homogeneously involved. The purpose of this study was to investigate the cerebral metabolic differences between patients with JME and normal controls. METHODS: All patients had a JME diagnosis based on seizure history and semiology, EEG recording, normal magnetic resonance neuroimaging (MRI) and video-EEG. Forty JME patients (JME-P) were submitted to 1.5 T MRI proton spectroscopy (1H-MRS), multi-voxel with PRESS sequence (TR/TE = 1500/30 ms) over the following locations: prefrontal cortex (PC), frontal cortex (FC), thalamus, basal nuclei, posterior cingulate gyrus (PCG), insular, parietal and occipital cortices. We determined ratios for integral values of N-acetyl aspartate (NAA) and glutamine-glutamate (GLX) over creatine-phosphocreatine (Cr). The control group (CTL) consisted of 20 age and sex-matched healthy volunteers. RESULTS: Group analysis demonstrated a tendency for lower NAA/Cr ratio of JME-P compared to CTL predominantly on FC, PC, thalamus and occipital cortex. When compared to CTL, JME-P had a statistically significant difference in GLX/Cr on FC, PC, insula, basal nuclei, PCG and on thalamus. When evaluating the relationship among the various components of this epileptic network among JME-P, the strongest correlation occurred between thalamus and PC. Also, we found a significant negative correlation between NAA/Cr and duration of epilepsy. CONCLUSION: Reductions in NAA may represent loss or injury of neurons and/or axons, as well as metabolic dysfunction while glutamate is considered to be an excitatory neurotransmitter in the brain which is involved in the pathogenesis of epileptogenic seizures.

Longitudinal Assessment of Cognitive Function in Patients with Juvenile Myoclonic Epilepsy / 대한간질학회지

BACKGROUND AND PURPOSE: We investigated the cognitive change of patients with juvenile myoclonic epilepsy (JME) after a long-term antiepileptic drug(s) (AED) administration to clarify the cause of cognitive impairment. METHODS: Thirty-three patients with JME who were newly diagnosed or did not take any AED for at least 6 months prior to the beginning of the study were included. We conducted neuropsychological tests at baseline and after at least 12 months of AEDs trial. Forty healthy controls were acquired according to age- and education-match to patients with JME. We compared the differences of neuropsychological outcomes among them. We tried to identify the determinants for cognitive performances after AEDs trial. RESULTS: Twenty-seven patients completed the second neuropsychological tests. Seizure frequency and EEG abnormality were significantly decreased after AEDs intake. The Number of epileptiform discharges (EDs) on EEG tended to be decreased at last visit. However, cognitive performances between baseline and follow-up period were not different. Cognitive measures of baseline and follow-up period were worse than those of controls in list learning, forward digit span, backward digit span, Trail Making Test, and verbal fluency. Cognitive performances of follow-up period in the JME group were not correlated with age at seizure onset, duration of epilepsy, seizure recurrence, EEG abnormality, and type of AEDs. CONCLUSIONS: Cognitive performances of JME were not recovered to the level of healthy controls despite the control of seizures and EDs by AEDs. Therefore, cognitive impairment of JME may be due to irreversible, disease-related characteristics.

Vasodepressive Response of Head-up Tilt-Table Test in Patients With Juvenile Myoclonic Epilepsy

BACKGROUND: Juvenile myoclonic epilepsy (JME) is characterized by myoclonic seizures on awakening and giant somatosensory evoked potentials. Those characteristics suggest that JME is related with dysfunction of the brainstem reticular formation. Cardiovascular reflex is also closely related with the brainstem reticular formation, and head-up tilt-table test (HUT) is frequently employed to evaluate the cardiovascular reflex. We performed HUT to assess the cardiovascular reflex in patients with JME and syncope/presyncope. METHODS: We included 52 patients with alleged JME. HUT was performed in 20 of them with a history of presyncope or syncope. The protocol of HUT included 70 degree table tilting test and isoproterenol infusion test (1~5 microgram/min). We determined the positive responses according to the change of blood pressure and heart rate. The positive responses were classified as vasodepressive, cardioinhibitory, or mixed types. We retrospectively analyzed the clinical findings and responses of HUT. RESULTS: Syncope or presyncope occurred during the seizure-prone situation in 3 (15%), and during the syncope-prone situation in 17 (85%) patients. Fifteen (75%) patients had positive responses in HUT. The positive responses were during the baseline test in 1 (5%), during the low dose (( or = 4 microgram/min) of isoproterenol infusion in the remaining 4 (20%) patients. All the positive responses were vasodepressive type. CONCLUSIONS: In patients with JME, vasomotor reflex may be impaired. Our results suggest dysfunction of the brainstem reticular formation in JME.

Juvenile myoclonic epilepsy

Juvenile myoclonus epilepsy (JME) is a common epileptic syndrome, the etiology of which is genetically determined. Its onset occurs from 6 through 22 years of age, and affected patients present with myoclonic jerks, often associated with generalized tonic-clonic seizures - the most common association - and absence seizures. JME is non-progressive, and there are no abnormalities on clinical examination or intellectual deficits. Psychiatric disorders may coexist. Generalized polyspike-and-waves are the most characteristic electroencephalographic pattern. Usual neuroimaging studies show no abnormalities. Atypical presentations should be entertained, as they are likely to induce misdiagnosis. Prevention of precipitating factors and therapy with valproic acid (VPA) are able to control seizures in the great majority of patients. Whenever VPA is judged to be inappropriate, other antiepileptic drugs such as lamotrigine may be considered. Treatment should not be withdrawn, otherwise recurrences are frequent.

A epilepsia mioclônica juvenil é uma síndrome epiléptica comum, cuja etiologia é fundamentada na genética. Inicia-se entre 6 e 22 anos e os indivíduos apresentam mioclonias, que podem ser acompanhadas por crises tônico-clônicas generalizadas - associação mais comum - e crises de ausência. A doença não é progressiva, e não há alterações detectáveis no exame físico ou déficits intelectuais. Distúrbios psiquiátricos podem coexistir. Polipontas-ondas lentas generalizadas constituem o padrão eletrencefalográfico ictal típico. Não há anormalidades em exames de imagem convencionais. Apresentações atípicas devem ser consideradas, pois predispõem a erros de diagnóstico. A prevenção de fatores desencadeantes e o uso de ácido valpróico (VPA) controlam as crises epilépticas na grande maioria dos casos. Quando o VPA é inapropriado, outras drogas como a lamotrigina podem ser utilizadas. O tratamento não deve ser interrompido, visto que as recidivas são freqüentes.

Cognitive Impairment in Juvenile Myoclonic Epilepsy

BACKGROUND AND PURPOSE: Cognitive impairments are frequent consequences of epilepsy, with intellectual ability reportedly being lower in patients with idiopathic generalized epilepsies than in the general population. However, neuropsychological investigations have been rarely performed in patients with juvenile myoclonic epilepsy (JME). We aimed to quantify the cognitive function in JME patients using various neuropsychological tests. METHODS: We compared cognitive function in 27 JME patients with that in 27 healthy volunteers using tests examining cognitive performance, such as the verbal and visual memory, frontal function, attention, IQ score, and mood. In the JME group, we examined risk factors for cognitive function such as age, sex, family history, education level, age at seizure onset, seizure frequency, EEG abnormality, disease duration, and previous intake of antiepileptic drugs. RESULTS: Verbal learning was significantly lower in JME patients than in controls, and attention and verbal fluency were impaired in JME patients compared with controls. However, general intellectual ability and mood did not differ between the groups. Early onset of seizure and long duration of disease were closely related to impaired cognitive function. CONCLUSIONS: JME patients may exhibit impaired cognitive function, in terms of memory and execution, despite having normal intelligence and mood.

Desempenho cognitivo de pacientes com epilepsia do lobo temporal e epilepsia mioclônica juvenil: avaliação por meio da Escala WAIS-III / Cognitive performance of patients with temporal lobe epilepsy and juvenile myoclonic epilepsy: evaluation through the Wechsler Intelligence Scale WAIS-III

OBJETIVOS: Comparar os resultados em uma prova cognitiva de pacientes com epilepsia com dois parâmetros: um fornecido pelas normas brasileiras e outro pelas norte-americanas, tendo em vista as diferenças culturais. MÉTODO: Quarenta e cinco pacientes adultos com diagnóstico de epilepsia foram submetidos à avaliação de nível intelectual por meio da Escala Wechsler de Inteligência, WAIS-III nos seguintes itens: Quociente de Inteligência Verbal (QI V), Quociente de Inteligência de Execução (QI E) e Quociente de Inteligência Total (QI T). As correções dos protocolos seguiram as normas brasileiras e as norte-americanas. RESULTADOS: Dos 45 pacientes, 30 tinham o diagnóstico de epilepsia do lobo temporal (ELT) por esclerose mesial temporal (EMT), 15 no hemisfério esquerdo e 15 no direito, e 15 de epilepsia mioclônica juvenil (EMJ). Em todos os 45 protocolos do WAIS-III os resultados de QI V, QI E e QI T foram maiores quando empregados os parâmetros brasileiros. Assim, 18 pacientes que alcançaram QI T nas faixas "Média" e "Média Inferior", segundo as normas brasileiras, obtiveram níveis inferiores quando corrigidos pelas normas norte-americanas, ou seja, o QI T destes mesmos pacientes caiu para as faixas "Limítrofe" e "Muito Rebaixado" respectivamente. Nos pacientes com ELT, as diferenças de pontos entre os QI V e QI E não foram concordantes quando cotejados por normas diferentes e em cinco deles o desempenho verbal foi maior do que o motor quando corrigidos pelas normas norte-americanas. Nos pacientes com EMJ, os valores do QI V e QI E foram maiores quando empregadas normas brasileiras. CONCLUSÃO: Os resultados da avaliação cognitiva pelo WAIS-III de pacientes com epilepsia mostram que a interpretação do nível intelectual é muito distinta quando corrigida segundo normas brasileiras ou norte-americanas. Há também diferença na análise qualitativa do desempenho intelectual, uma vez que o estudo das discrepâncias internas variou conforme a norma populacional utilizada.

To compare the results of a cognitive task of patients with epilepsy with two parameters: one provided by the Brazilian and the other by the US normative scores viewing the cultural differences. METHOD: Forty-five adult patients diagnosed with epilepsy were submitted to intellectual evaluation through the Wechsler Adult Intelligence Scale, WAIS-III, in the following items: Verbal Intelligence Quotient (V IQ), Performance Intelligence Quotient (P IQ) and Full Scale (FS IQ). The correction of the protocols followed the Brazilian and the US normative scores. RESULTS: Thirty out of the 45 patients were diagnosed with temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS), 15 in the left hemisphere and 15 in the right, and 15 with juvenile myoclonic epilepsy (JME). In all 45 WAIS protocols the results of the V IQ, P IQ and FS IQ were higher when the Brazilian parameters were employed. Therefore, 18 patients that achieved FS IQ in the "Average" and "Low Average" ranges, according to the Brazilian normative scores, got lower levels when corrected by the US normative scores, that is, the FS IQ of these 18 patients fell to the æBorderlineÆ and æExtremely LowÆ ranges respectively. In the patients with TLE, the differences in the scores between the V IQ and P IQ did not correspond when evaluated by different normative scores and in five of them the verbal was higher than the performance when corrected by the US normative scores. In the patients with JME, the values of V IQ and P IQ were higher when the Brazilian normative scores were employed. CONCLUSION: The results of the cognitive evaluation through the WAIS of patients with epilepsy showed that interpretation of the intellectual level is very dissimilar when corrected by the Brazilian or US normative scores. There is also a difference in the qualitative analysis of the intellectual performance since the study of the inner discrepancy varied according the population normative scores employed.

Structural Brain Abnormalities in Juvenile Myoclonic Epilepsy Patients: Volumetry and Voxel-Based Morphometry

OBJECTIVE: We aimed to find structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients. MATERIALS AND METHODS: The volumes of the cerebrum, hippocampus and frontal lobe and the area of the corpus callosum's subdivisions were all semi-automatically measured, and then optimized voxel-based morphometry (VBM) was performed in 19 JME patients and 19 age/gender matched normal controls. RESULTS: The rostrum and rostral body of the corpus callosum and the left hippocampus were significantly smaller than those of the normal controls, whereas the volume of the JME's left frontal lobe was significantly larger than that of the controls. The area of the rostral body had a significant positive correlation with the age of seizure onset (r = 0.56, p = 0.012), and the volume of the right frontal lobe had a significant negative correlation with the duration of disease (r = -0.51, p = 0.025). On the VBM, the gray matter concentration of the prefrontal lobe (bilateral gyri rectus, anterior orbital gyri, left anterior middle frontal gyrus and right anterior superior frontal gyrus) was decreased in the JME group (corrected p < 0.05). CONCLUSION: The JME patients showed complex structural abnormalities in the corpus callosum, frontal lobe and hippocampus, and also a decreased gray matter concentration of the prefrontal region, which all suggests there is an abnormal neural network in the JME brain.