White matter changes associated with feline GM2 gangliosidosis (Sandhoff disease): correlation of MR findings with pathologic and ultrastructural abnormalities.

PURPOSE To establish changes on MR of the brain in a feline model of Sandhoff disease in order to develop standards by which this model may be used in future noninvasive studies.

METHODS Five affected felines and six age-matched, littermate controls were evaluated. T1- and T2-weighted images were obtained once or twice for each of four affected and five control animals at 4 1/2 to 12 weeks of age, for a total of 15 MR examinations. Images were evaluated qualitatively for the pattern of myelination and the size of the ventricular system. After the animals were killed, pathologic specimens of the brain were examined with light and electron microscopy, and pathologic changes were correlated with MR.

RESULTS Compared with control animals, affected animals showed MR evidence of delayed myelination, manifested by white matter signal hypointensity on T1-weighted images and signal hyperintensity on T2-weighted images. This finding was corroborated by histopathologic findings of decreased myelin in the subcortical and internal capsule regions. White matter abnormalities were not detected ultrastructurally in the animals examined.

CONCLUSION Although GM2 gangliosidosis is primarily a neuronal disease, MR imaging can show changes in myelination of white matter tracts that may be secondary to the neuronal damage. This provides a noninvasive method of in vivo monitoring as therapeutic strategies are developed in this animal model.