ABSTRACT
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.
Subject(s)
Humans , Magnetic Resonance Imaging , Epilepsies, Myoclonic , Myoclonic Epilepsy, Juvenile , Proton Magnetic Resonance SpectroscopyABSTRACT
OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of topiramate (TPM) in juvenile myoclonic epilepsy (JME). METHOD: We assessed seizure control and adverse effects of TPM in 22 patients (18 females) aged 13 to 53 years. Target TPM dosage was up to 200 mg/day. The patients were subdivided into 3 groups: those treated with seizure control plus side effects (n=4); treated with non-controlled seizures (n=15) and with JME newly diagnosed (n=3). RESULTS: Sixteen patients completed the first year of the follow-up. Generalized tonic-clonic seizures were completely controlled in 10 (62.5%); more than 50% of reduction in 4 (25.0%) and less than 50% in 2 (12.5%). Myoclonia were controlled in 11 (68.8%) and persisted in 5 (31.2%) patients. Absence seizures were present in 5 (22.7%) of whom 2 (9.0%) showed more than 50% of seizure reduction while 3 (13.6%) presented worsening. Discontinuations were due to inadequate seizure control and adverse events (N=4), low compliance and loss of follow-up (N=2) and subject choice (N=1). CONCLUSION: TPM showed to be an effective and well-tolerated drug in the treatment of JME. Although frequently observed, TPM side effects were tolerable and the drug could be maintained in the majority of patients.
OBJETIVO: Avaliar a eficácia e tolerabilidade do topiramato (TPM) na epilepsia mioclônica juvenil (EMJ). MÉTODO: Avaliamos a resposta terapêutica e efeitos colaterais do TPM em 22 pacientes (18 mulheres) com idades entre 13 e 53 anos. A dose alvo utilizada foi até 200 mg/dia. Os pacientes foram divididos em 3 grupos no início do tratamento: aqueles com controle das crises mas que apresentavam efeitos colaterais (n=4); com crises não controladas (n=15) e com EMJ recém diagnosticada (n=3). RESULTADOS: Dezesseis pacientes completaram o primeiro ano de acompanhamento. Crises tônico-clonicas generalizadas foram completamente controladas em 10 (62,5%), tiveram redução maior de 50% em 4 (25,0%) e menor de 50% em 2 (12,5%). Mioclonias foram controladas em 11 (68,8%) e persistiram em 5 (31.2%) pacientes. As crises de ausências, presentes em 5 (22,7%) pacientes, tiveram redução maior do que 50% em 2 (9,0%) e agravamento em 3 (13,6%). A retirada do estudo foi devida principalmente ao controle inadequado das crises e efeitos colaterais indesejáveis (n=4), pouca adesão e perda do seguimento (n=2) e escolha do paciente (n=1). CONCLUSÃO: TPM foi considerada droga eficaz e bem tolerada no tratamento da EMJ. Apesar de freqüentemente observados, os efeitos colaterais do TPM foram toleráveis e a medicação pode ser mantida na maioria dos pacientes.