Diagnosis:
Genetics:
- Autosomal dominant
- DRPLA gene chr. 12. CAG repeat expansion (normal repeat number is 6-35). Protein= atrophin-1 protein.
Clinical features:
- Chorea, ataxia, dementia, myoclonus
Pathology:
Gross: diffuse brain atrophy, worse in pons and cerebellum. Atrophy & discolouration of the globus pallidus, dentate nucleus, subthalamus & pontine tegmentum.
Microscopic: neuronal loss of dentate nucleus with grumose degeneration (eosinophilic granular material near the bodies of dentate neurons, it consists of preterminal axons). Neuronal loss & astrocytosis of external globus pallidus.
Neuronal loss also in: red nucleus, caudate, putamen, substantia nigra, subthalamus.
White matter degeneration of: cerebellar/olivary complex, superior cerebellar complex, posterior columns, spinocerebellar tracts.
Eosinophilic neuronal inclusions. Cytoplasmic inclusions in dentate nucleus neurons.
Immunohistochemistry: atrophin-1 positive intranuclear inclusions, ubiquitin positive intranuclear inclusions & cytoplasmic inclusions.