Alexander disease

Alexander disease is a rare disorder with limited understanding of its cause, although it does seem to be a disorder of astrocytes rather than a leukodystrophy. It can be divided into three groups: infantile, juvenile, and adult. The infantile type shows enlargement of the head, retarded development and evidence of a severe neurological disorder. The juvenile sufferers are more likely to exhibit bulbar signs, and may-not be significantly retarded. Among adults the condition can fluctuate, and so mimic multiple sclerosis. The differential diagnosis in these three groups is discussed, especially the unusual ways in which they can present. The definitive diagnosis may depend on demonstrating Rosenthal fibres in a brain biopsy, or at autopsy, but other tests can be suggestive. The cerebrospinal fluid can show an elevation of B-crystallin and heat shock protein, and the GFAP gene is considered a reliable marker. The EEG and magnetic imaging findings are non-specific. Pathological studies of the brain can be characteristic with demyelination, especially in the frontal lobes, and Rosenthal fibres concentrated in the subpial. and subependymal areas. It is possible that these fibres cause a dysfunction of the astrocytes. The genetic investigations are reviewed, and possible causes are discussed. These remain theoretical, but it has been suggested that the disorder is a response to stress from some unknown stimulus. Rosenthal fibres seem to be the result of the condition, although they may be related to the aetiology. There is no specific treatment. (C) 2003 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.