Specific Imaging Findings

The most common infantile form of Alexander disease (AD) is characterized by frontotemporal white matter abnormalities (CT hypodense, low T1 and high T2 signal) with typical anteroposterior progression pattern, involvement of U-fibers and possible cystic degeneration. The external and extreme capsules are usually involved. There are characteristic T1 hyperintense and T2 hypointense periventricular frontal rims, hyperdense on CT. The deep gray matter may be swollen and T2 hyperintense showing gradual volume loss. Brainstem abnormalities are primarily involving the medulla and midbrain. Contrast enhancement is seen in ventricular ependyma, periventricular rim, frontal white matter, optic chiasm, fornix, basal ganglia, thalamus, dentate nucleus, and brainstem. Hydrocephalus may occcur due to aqueductal stenosis. Atypical MRI findings are more commonly observed in juvenile and adult AD and include: predominant or isolated involvement of posterior fossa, multifocal tumor-like brainstem lesions, signal abnormalities or atrophy of the medulla or spinal cord and garland-like features along the ventricular wall. MRS may show markedly decreased NAA, with increased myo-inositol, choline, and lactate.

Pertinent Clinical Information

There are three clinical subgroups of AD: infantile (birth to 2 years), juvenile (2–12 years), and adult forms. Infantile AD presents with increasing macrocephaly, failure of normal development, seizures, serious feeding problems, and rapid neurologic deterioration with average survival of 3 years. In juvenile AD, macrocephaly is less frequent and patients usually suffer from progressive signs of bulbar dysfunction, developmental regression, ataxia and spasticity with average survival of 8 years.