Clinical study of childhood acute disseminated encephalomyelitis, multiple sclerosis, and acute transverse myelitis in Fukuoka Prefecture, Japan.

Acute disseminated encephalomyelitis (ADEM) has recently been studied in several countries owing to the development and wide spread use of imaging technology, but few epidemiological studies of childhood ADEM have been undertaken in Asian countries. To perform a comprehensive survey of ADEM and related diseases in Japanese children, we conducted a multicenter, population-based study on childhood ADEM, multiple sclerosis, and acute isolated transverse myelitis in Fukuoka Prefecture, Japan. We identified 26 children with ADEM, 8 with multiple sclerosis, and 4 with acute transverse myelitis during 5 years between September 1998 and August 2003. The incidence of childhood ADEM under the age of 15 years was 0.64 per 100,000 person-years, mean age at onset was 5.7 years, and male-female ratio was 2.3:1. The prevalence of childhood multiple sclerosis was 1.3 per 100,000 persons. The mean age at onset of multiple sclerosis, 9.3 years, was significantly higher than that of ADEM. Nineteen (73%) and four (15%) patients with ADEM experienced antecedent infectious illnesses and vaccinations, respectively, within 1 month before the onset. Clinical and radiological findings of ADEM revealed that the frequency of seizures, mean white blood cell counts in cerebrospinal fluid, and the frequency of subcortical lesions in Fukuoka study, seemed to be higher than those in previous non-Asian studies. These findings suggest that there are ethnic or geographical differences in the incidence and clinical features of ADEM, and that there might be potent genetic or environmental risk factors for ADEM distinct from those for multiple sclerosis.

[Genetics of epilepsy].

Epilepsy is a common neurological disease and encompasses a variety of disorders with paroxysms. Although there is a genetic component in the pathogenesis of epilepsy, the molecular mechanisms of this syndrome remain poorly understood. The identification of genes responsible for human epilepsy was first documented in progressive myoclonic epilepsy (EPM) because of their clear inheritance and phenotypic presentation. EPM is characterized by frequent myoclonic jerks and cumulative neurological deterioration and includes MERRF, a mitochondrial disease and DRPLA, a triplet disorder. The genes responsible for EPM seem to participate in the maintenance of cell viability. Genetic defects have been recently identified also for some familial epilepsy in which the phenotypes are similar to common idiopathic epilepsies. Defects of neuronal nicotinic acetylcholine receptor, a ligand-gated ion channel, caused nocturnal frontal lobe epilepsy. Mutations of two K(+)-channel genes were identified in benign familial neonatal convulsions. Mutations in the voltage-gated Na(+)-channel alpha 1, 2 and beta 1 and the GABAA receptor gamma 2 subunit genes were found as a cause of dominant epilepsy with febrile seizures plus, a clinical subset of febrile seizures. Abnormalities of Na(+)-channel alpha 1 subunit were also associated with severe myoclonic epilepsy in infancy. Other genes encoding ion channels expressed in the brain were also found to be associated with other familial epilepsy. This line of evidence suggests the involvement of channels expressed in the brain in the pathogenesis of certain idiopathic epilepsy, albeit there are a few exceptions that abnormalities of non-channel molecules have been found to be associated with idiopathic epilepsy.