Alexander disease: diagnosis with MR imaging

Abstract

Background and purpose: To date, the demonstration of Rosenthal fibers on brain biopsy or autopsy specimens is considered a prerequisite for a definitive diagnosis of Alexander disease. We initiated a multiinstitutional survey of MR abnormalities in both presumed and confirmed cases of Alexander disease to assess the possibility of an MR-based diagnosis.

Methods: MR imaging studies in three patients with an autopsy-based diagnosis of Alexander disease were analyzed to define MR criteria for the diagnosis. These criteria were then applied to 217 children with leukoencephalopathy of unknown origin.

Results: Five MR imaging criteria were defined: extensive cerebral white matter changes with frontal predominance, a periventricular rim with high signal on T1-weighted images and low signal on T2-weighted images, abnormalities of basal ganglia and thalami, brain stem abnormalities, and contrast enhancement of particular gray and white matter structures. Four of the five criteria had to be met for an MR imaging-based diagnosis. In a retrospective analysis of the MR studies of the 217 patients, 19 were found who fulfilled these criteria. No other essentially new MR abnormalities were found in these patients. In four of the 19 patients, subsequent histologic confirmation was obtained. The clinical symptomatology was the same in the patients with and without histologic confirmation and correlated well with the MR abnormalities. MR abnormalities were in close agreement with the known histopathologic findings of Alexander disease.

Conclusion: The defined criteria are sufficient for an in vivo MR imaging diagnosis of Alexander disease; only in atypical cases is a brain biopsy still necessary for a definitive diagnosis.

fig 1.

Early MR imaging study at the age of 4 months in a patient with autopsy-proved infantile Alexander disease. A–D, T2-weighted images show abnormally high signal in the medulla (A), the hilus of the dentate nucleus (arrows, A), the entire midbrain except for the red nuclei (B), the basal ganglia, and the thalamus (C). The frontal white matter has a slightly higher signal intensity than the occipital white matter (C). The head of the caudate nucleus is swollen (arrowheads, C). Around the ventricles, there is a rim of low signal intensity (arrows, B–D). E–G, T1-weighted images show high signal intensity of the periventricular rim (arrows, E). After contrast administration, the T1-weighted images show enhancement of areas in the midbrain (F), ventricular lining (arrows, F), and periventricular rim (arrows, G).

fig 2.

A–D, Early (A) and late (B–D) MR studies of a patient with autopsy-confirmed juvenile Alexander disease, obtained at ages 20 months (A) and 9 years (B–D). The early T2-weighted image (A) shows extensive cerebral white matter abnormalities with partial sparing of the occipital region. There is a thin periventricular rim of low signal intensity (arrows, A). The basal ganglia and thalamus have an increased signal intensity. The putamen and caudate nucleus are mildly swollen (A). On follow-up, the extent of the cerebral white matter abnormalities is more or less the same; the occipital white matter is still partially spared (D). The basal nuclei are dark and atrophic on the T2-weighted images (D). A thin periventricular rim of low signal intensity is visible (arrows, D). The proton density–weighted image (C) shows enormous cysts in the frontoparietal white matter, a large cavum vergae, and enlarged lateral ventricles. A lesion is seen in the posterior part of the medulla (B)

fig 3.

MR imaging of a patient with biopsy-confirmed infantile Alexander disease. A and B, At the age of 1½ months, the frontal white matter has a slightly higher signal intensity on T2-weighted images and slightly lower signal intensity on unenhanced T1-weighted images than does the remainder of the cerebral white matter, which has normal signal intensity for unmyelinated white matter. There is a periventricular rim of low signal intensity on T2-weighted images (arrows, A) and high signal intensity on T1-weighted images (arrows, B), with some extensions into the frontal white matter (arrowheads, A and B). The caudate nucleus and putamen have high signal intensity on T2-weighted images and are mildly swollen. C and D, At the age of 3 months, a major increase in ventricular size is seen with extreme thinning of the posterior cerebral mantle. The frontal white matter has a more abnormal signal intensity than the occipital white matter, appears markedly swollen, and shows early cystic degeneration (arrows, D). There is a thin periventricular rim of low signal intensity on T2-weighted images (arrows, C). The basal ganglia are now markedly atrophic. After contrast administration, enhancement occurs in the ventricular lining, caudate nucleus, putamen, frontal white matter, and parts of the frontal cortex (D).

fig 4.

Early MR imaging studies in a patient with presumed juvenile Alexander disease, obtained at the age of 4 years. A and B, Extensive cerebral white matter abnormalities are seen on these T2-weighted images (B), with sparing of the occipital U fibers (arrows, B). The signal abnormality is more pronounced in the frontal than in the occipital white matter. There is an irregular periventricular rim of low signal intensity (arrowheads, B). The basal ganglia and thalamus have a mildly increased signal intensity. Within the posterior fossa, signal abnormalities are seen in the central part of the medulla, the hilus of the dentate nucleus, and the cerebellar hemispheric white matter, characteristically with the normal dentate nucleus prominently visible in between (A). fig 5. Contrast-enhanced MR image in a patient with presumed juvenile Alexander disease, obtained at the age of 12 years. Note enhancement of the intraparenchymal trajectory of the fifth cranial nerve on both sides

fig 6.

Late MR imaging study of a patient with presumed juvenile Alexander disease, obtained at the age of 10 years. A and B, There is extensive white matter involvement with frontal preponderance (A). The basal ganglia are dark and atrophic on T2-weighted images (A). A thin periventricular rim of low signal intensity is just visible (arrows, A). After contrast administration, enhancement of the entire cerebellar surface and dentate nucleus is seen (B).