Cerebellar lesions in multiple system atrophy: postmortem MR imaging-pathologic correlations

Abstract

Background and purpose: Cerebellar atrophy and white matter T2-hyperintensities have been characterized as cerebellar lesions of multiple system atrophy (MSA). The aim of the study was to correlate MR images with histologic findings in cerebellar lesions of MSA.

Materials and methods: Postmortem T2-weighted images using 1.5T were compared with histologic findings in 7 postmortem-proved cases with MSA. The MR imaging findings in the cerebellar cortices and deep white matter dentate nucleus regions were compared with their histologic findings in each case.

Results: We detected 3 types of cerebellar changes: type 1, no apparent atrophy or signal-intensity changes; type 2, cerebellar atrophy and inhomogeneous (patchy and/or confluent) cerebellar white matter hyperintensities; and type 3, cerebellar atrophy and diffuse white matter hyperintensities. Hypointensities were seen in the dentate nucleus regions. Atrophy of the cerebellar white matter was more severe than that of cerebellar cortices, and this anatomy was well depicted on coronal images. Histologically, degeneration was more severe in the cerebellar white matter than in the cerebellar cortices. Hyperintensities in the cerebellar white matter showed loss of myelinated fibers and gliosis. Hypointensities in the dentate nucleus regions revealed diffuse ferritin deposition in preserved dentate nuclei and white matter both around and within the nuclei.

Conclusions: Hyperintensities in the cerebellar white matter reflect degenerated white matter associated with loss of myelinated fibers and gliosis, whereas hypointensities in the dentate nucleus regions reflect diffuse ferritin deposition in preserved dentate nuclei and white matter around and within the nuclei. Degeneration is more severe in the cerebellar white matter than in the cerebellar cortices.

Fig 1.

Case 1 (type 1). A and B, Postmortem axial (A) and coronal (B) T2-weighted images show no apparent cerebellar atrophy or signal-intensity changes. Note the convex contour of the cerebellar deep white matter on the coronal image (arrowheads in B). No signal-intensity changes or atrophy is seen in the middle cerebellar peduncles or pontine base. Hypointensities are seen in the dentate nucleus regions. Cerebellar cortices, deep white matter, and dentate nucleus regions are depicted well on the coronal image (B) compared with the axial image (A). C, A myelin-stained section corresponding to the white boxed area in B shows mild pallor in the deep cerebellar white matter (arrowheads). Dentate nucleus and white matter within and surrounding the dentate nucleus are well preserved (arrows) (Klüver-Barrera stain, original magnification ×5). D and E, Histologic finding of the boxed area in C shows mild loss of myelin (D) and axons (E) with mild gliosis (Klüver-Barrera stain, original magnification ×200, D; Bielschowsky stain, original magnification ×200, E). F, Immunohistochemical findings of the dentate nucleus (circled area in C) show diffuse ferritin deposition and well-preserved neurons (arrows) (ferritin stain, original magnification ×200).

Fig 2.

Case 2 (type 2). A and B, Postmortem axial (A) and coronal (B) T2-weighted images show atrophied cerebellar cortices with dilation of folial fissures and atrophied deep cerebellar white matter with a concave contour (arrowheads in B). Note the confluent hyperintensities in the cerebellar deep white matter (arrows in B). Hypointensities are seen in the dentate nucleus regions (A and B). There are diffuse hyperintensities and atrophy in the middle cerebellar peduncles and crossed hyperintensities and atrophy in the pontine base (A). Cerebellar deep white matter and dentate nucleus regions are not depicted precisely on the axial image (A), due to partial volume effects of water seen in dilated folial fissures. C, A myelin-stained section corresponding to the white boxed area in B shows pallor in the deep cerebellar white matter (arrowheads). Dentate nucleus and white matter within and surrounding the dentate nucleus are well preserved (arrows) (Klüver-Barrera stain, original magnification ×5). D and E, Histologic finding of the boxed area in C shows loss of myelin (D) and axons (E) with gliosis (Klüver-Barrera stain, original magnification ×200, D;. Bielschowsky stain, original magnification ×200, E). F, Immunohistochemical finding of the dentate nucleus (circled area in C) shows diffuse ferritin deposition and well-preserved neurons (arrows) (ferritin stain, original magnification ×200).

Fig 3.

Case 5 (type 3). A and B, Postmortem axial (A) and coronal (B) T2-weighted images show atrophied cerebellar cortices with dilation of folial fissures and atrophied deep cerebellar white matter with a concave contour (arrowheads in B). Note the diffuse hyperintensities in the deep cerebellar white matter (arrows in B). There are diffuse hyperintensities and atrophy in the middle cerebellar peduncles and crossed hyperintensities and atrophy in the pontine base (A). Cerebellar deep white matter and dentate nucleus regions are not depicted precisely on the axial image (A). Hypointensities of the dentate nucleus region are conspicuous due to diffuse hyperintensities of the cerebellar deep white matter (B). C, A myelin-stained section corresponding to the white boxed area in B shows the diffuse pallor of the deep cerebellar white matter (arrowheads). Mild atrophy of the dentate nucleus and mild pallor of the white matter within and surrounding the dentate nucleus are seen (arrows) (Klüver-Barrera stain, original magnification ×5). D and E, Histologic findings of the boxed area in C show tissue rarefaction associated with loss of myelin (D) and axons (E) as well as gliosis (Klüver-Barrera stain, original magnification ×200, D; Bielschowsky stain, original magnification ×200, E). F, Immunohistochemical findings of the dentate nucleus (circled area in C) show diffuse ferritin deposition and preserved neurons with atrophy (arrows) (ferritin stain, original magnification ×200).