Alexander disease--classification revisited and isolation of a neonatal form

Abstract

Alexander disease is usually classified according to the age of onset, e.g. an infantile form with onset during the first two years of life, a juvenile form with onset in childhood, mainly school age. It has been recognized, however, that the clinical course can be very variable within these groups. Thus, this clinical classification is not a useful predictor of severity and progression of the disease. This is demonstrated here on the basis of the history of seven own patients and a literature review. Only an onset in very early infancy, during the neonatal period, seemed to be associated with a rather uniform pattern of disease course, often leading to early death. This neonatal form showed very stereotyped symptoms, in part different from later onset: Early, often intractable, generalized seizures; hydrocephalus with raised intracranial pressure due to aqueductal stenosis because of pathological astroglia proliferation; lack of developmental progression but without prominent spasticity or ataxia; elevated CSF protein content. This was associated with the well-established neuroradiological findings, e.g. severe white matter affection with fronto-temporal predominance, involvement of basal ganglia and periventricular enhancement as an obligatory symptom. The identification of this early onset form is especially important as seizures and signs of raised intracranial pressure may mislead the diagnosis.