Investigators from Mayo Clinic, Rochester, MN, retrospectively identified 13 patients with type II Alexander disease (AxD) evaluated from Jan 1996 to Feb 2012. Median age at onset was 38 years (range 12-63); 5 were female. Neuroimaging data showed that 11 patients had atrophy of the medulla, all 13 had medullary T2 hyperintensity, 5 had T2 signal changes in the middle cerebellar peduncle, and 11 had pial FLAIR signal change in the medulla. Spinal cord imaging in 12 patients showed cord atrophy in 9, and 3 had cervical cord enhancement. Eight subjects had tadpole atrophy (atrophy of the medulla and cervical spinal cord with relative sparing of the pons). Three patients had thalamic or basal ganglia signal abnormality. Three patients had garland-like feature along the ventricular wall (ependymal nodularity), but to a lesser degree than that reported in infantile AxD. Compared with infantile or type 1 AxD, involvement of the periventricular white matter was sparse. Eight patients had mutations in the GFAP gene. Ten patients had a positive family history of probable AxD. Biopsy of the middle cerebellar peduncle in 1 patient demonstrated excessive Rosenthal fiber deposition in gray and white matter, consistent with a diagnosis of AxD. An autopsy on patient 2 showed severe atrophy of medulla and spinal cord with Rosenthal fiber deposition. [1]

COMMENTARY. Alexander disease is characterized as infantile, juvenile, and adult forms or as type I with early-onset or type II of late-onset. MRI features of infantile type I consist of frontal white matter changes, a periventricular rim, and signal abnormality involving the basal ganglia, thalamus, and brainstem. The imaging features of type II late-onset AxD are different from those of type I and show predominant brainstem involvement with significant atrophy of the medulla, middle cerebellar peduncle, and spinal cord. The differential diagnosis of involvement of the middle cerebellar peduncle include AxD type II, spinocerebellar ataxia, Wilson disease, liver cirrhosis, adrenoleukodystrophy, and neoplasm. Palatal tremor (palatal myoclonus) is suggestive of late-onset AxD [2] but was rare in the Mayo Clinic series.