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.

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.

Neurophysiological characteristics of Lafora's Disease

Avaliamos as características neurofisiológicas (EEG e potenciais evocados) de 2 pacientes na fase III da doença de Lafora, No EEG, desorganizaçäo da atividade de base foi associada a descargas epileptiformes difusas e bilaterais, com acentuaçäo em regiöes pccipitais onde também ocorreram descargas isoladas nos exames de ambos os pacientes. Resposta fotoconvulsiva foi evidenciada nos 2 casos e, em 1 deles, foram registradas descargas occipitais seguindo a estimulaçäo fótica com baixa frequência (1-3 flashes/s) correspondendo a grande amplitude de N2-P2 na resposta evocada visual por flash

MRI and brain SPECT findings in patients with unilateral temporal lobe epilepsy and normal CT scan

Foram estudados 26 pacientes com epilepsia do lobo temporal clinicamente documentada por vários EEGs com atividade epileptiforme intercrítica e TC de crânio normal SPECT com TC HMPAO e ressonância magnética (RM) foram realizados em todos os casos 61,5 por cento (n=17) dos SPECTs revelaron algum tipo de anormalidade. Atrofia hipocampal, nas imagens enfatizadas em T1 e presença de hipersinal nas imagens enfatizadas em T2, sugerindo esclerose mesial temporal, foram o principal achado (n=12,75 por cento das RM anormais). RM correlacionou-se ao ECG em 50 por cento (n=13). Concordância entre RM e SPECT ocorreu em 30.7 por cento (n=8) e entre SPECT e EEG em 57.7 por cento (n=15), RM, SPECT e EEG foram congruentes em 26.9 por cento (n=7). Estes resultados refletem o valor do SPECT intercrítico e RM na detecçäo e lateralizaçäo de anormalidades em epilepsia do lobo temporal. Por outro lado, em dois casos, o SPECT correlacionou-se mal com o EEG. Este método funcional näo deve ser utilizado isoladamente na detecçäo de focos temporais. RM é mais útil do que a TC como recurso de neuroimagem na epilepsia do lobo temporal. Ela pode detectar pequenas lesöes estruturais e esclerose mesial temporal, näo facilmente identificáveis pela TC

Características clínicas de pacientes com epilepsia temporal e esclerose mesial / Clinical characteristcs of patients with temporal lobe epilepsies and mesial sclerosis

Entre as epilepsias do lobo temporal, a síndrome temporal mesial é caracterizada por manifestaçöes clínicas homogêneas e achados específicos em exames paraclínicos. Descrevemos características clínicas de 22 pacientes, com 14 a 51 anos de idade (média 31,8 anos) e duraçäo da epilepsia de 6 a 41 anos (média 22,08 anos), com epilepsia do lobo temporal e sinais de esclerose mesial na RM e/ou no estudo anátomo-patológico. Crises epilépticas nos primeiros anos de vida estavam presentes em 19 (86,3 por cento ) dos pacientes; dentre estas, 11 foram convulsöes febris (em 10 complicados), as quais, quando apresentaram manifestaçöes motoras dimidiadas, constituíram importante dado para a lateriazaçäo da área epileptogênica, sendo sempre contralaterais ao lado da esclerose mesial temporal. Ocoreu intervalo livre de 8 meses a 24 anos (média 7,58 anos) entre o possível fator etiológico e o aparecimento de crises recorrentes sugestivas de epilepsia temporal, que incluiam crises parciais simples, com manifestaçöes viscerais, e crises parciais complexas, durante as quais sinais motores lateralizados foram importantes na lateralizaçäo do lobo epileptogênico de 9/71 pacientes. Crises tônico-clônicas generalizadas infreqüentes foram relatadas por 13 pacientes (59 por cento ), ocorrendo geralmente no início da epilepsia