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White matter changes associated with feline GM2 gangliosidosis (Sandhoff disease): correlation of MR findings with
R A Kroll1, M A Pagel, S Roman-Goldstein
1Department of Neurology, Oregon Health Sciences University, Portland 97201-3098, USA.
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.
Insights
Magnetic resonance (MR) imaging reveals delayed myelination in Sandhoff disease felines, offering a noninvasive method for monitoring disease progression in this animal model.
Area of Science:
- Neuroscience
- Veterinary Medicine
- Medical Imaging
Background:
- Sandhoff disease is a rare, fatal neurodegenerative lysosomal storage disorder.
- It is characterized by the accumulation of GM2 gangliosides in neurons.
- Current understanding of disease progression relies on invasive methods.
Purpose of the Study:
- To characterize brain magnetic resonance (MR) changes in a feline model of Sandhoff disease.
- To establish MR imaging standards for noninvasive monitoring in future studies.
- To correlate MR findings with histopathology.
Main Methods:
- MR imaging (T1- and T2-weighted) was performed on five affected and six control felines aged 4.5 to 12 weeks.
- Qualitative assessment of myelination patterns and ventricular system size.
- Post-mortem histopathological examination (light and electron microscopy) of brain tissue.
Main Results:
- Affected felines exhibited delayed myelination, evidenced by T1 hypointensity and T2 hyperintensity in white matter.
- Histopathology confirmed reduced myelin in subcortical and internal capsule regions.
- Ultrastructural analysis did not reveal white matter abnormalities.
Conclusions:
- MR imaging can detect white matter myelination changes secondary to neuronal damage in Sandhoff disease.
- This provides a noninvasive in vivo method for monitoring disease progression.
- The feline model offers a valuable platform for developing and testing therapeutic strategies.