Alexander disease:clinical features and pathophysiology

Tomokatsu Yoshida

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine

Recently, glial fibrillary acidic protein (GFAP) mutation was confirmed in reported cases of Alexander disease (AxD). We conducted a nationwide survey and a clinical study, and classified AxD into three types:cerebral AxD (Type 1), with the presence of seizures, psychomotor developmental retardation, macrocephaly, and abnormalities in the superior frontal cerebral white matter observed on brain MRI;bulbospinal AxD (Type 2), with motor and bulbar symptoms, and signal abnormalities and atrophy observed on MRI of the medulla oblongata;and an intermediate form (Type 3). Recent research in vivo and in vitro has suggested that the pathology of AxD involves not only functional abnormalities in intermediate filaments but also those in astrocytes. Several studies on treatment have been reported, but numerous issues have to be resolved prior to clinical application.

Address correspondence to Dr. Tomokatsu Yoshida, Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine (465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan)