Seven patients with atypical Alexander disease, showing signs of medulla and spinal cord involvement and little evidence of leukoencephalopathy, are reported from University Medical Center, Amsterdam, the Netherlands; and centers in the UK, USA, Canada, and Sweden. Patient 1 presented with progressive spinal cord dysfunction at age 9 years. Spinal MRI showed thickening of the spinal cord, and brain MRI revealed medulla and dentate nucleus changes, with a garland appearance lining the lateral ventricles. Rosenthal fibers consistent with Alexander disease were found in perivascular and subependymal regions of the ventricular wall biopsy. Diagnosis was confirmed by genetic testing and de novo mutations in the GFAP gene. All patients had juvenile onset and signs of brain stem and spinal cord dysfunction or atrophy; none had macrocephaly. [1]

COMMENT. Alexander disease, a rare leukoencephalopathy caused by mutations in the GFAP gene, is characterized by white matter abnormalities, predominantly affecting the frontal lobes. The disease typically occurs in infants with macrocephaly and delayed development. Since DNA confirmation of the diagnosis, the clinical and MRI phenotype has widened to include cases with predominant brainstem and spinal cord involvement, usually of late onset. Signal abnormalities or atrophy of these locations should warrant DNA analysis for Alexander disease. An MRI appearance of ventricular garlands, a relatively new sign, is also an indication for DNA confirmation.