Dentatorubral-Pallidoluysian Atrophy (DRPLA)
General description
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder caused by an abnormal expansion of CAG repeats in the Atrophin 1 gene. The disease exhibits anticipation, with the age of onset ranging from childhood to middle age, and its clinical manifestations vary depending on the age at which symptoms appear.
In individuals younger than 20 years, DRPLA is characterized by myoclonus, epilepsy, cerebellar ataxia, intellectual disability, behavioral changes, speech difficulties, sleep disturbances, and sensory hypersensitivity. These symptoms are often severe and may be resistant to treatment.
For those who develop the disease between their 20s and 40s, symptoms include a combination of early-onset and late-onset features. This may involve choreoathetosis, progressive dementia, psychiatric symptoms such as delusions and personality changes, and cerebellar ataxia. Seizures may occur but are less common than in the juvenile form.
In individuals older than 40 years, DRPLA primarily presents with cerebellar ataxia and chorea, along with progressive cognitive decline and psychiatric disturbances.
References
- Kurokawa, Ryo, et al. "Clinical and neuroimaging review of triplet repeat diseases." Japanese Journal of Radiology 41.2 (2023): 115-130.
Atrophy
-
Cerebrum
-
Cerebellum
-
Brainstem
-
Middle cerebellar peduncle
In the late adult type, atrophy is observed in multiple regions including the cerebellum, brainstem, cerebrum, and bilateral middle cerebellar peduncles.
Conversely, the early onset type primarily exhibits cerebellar atrophy, with progression leading to additional brainstem and cerebral atrophy.
The early adult type presents a combination of features from both the early onset and late adult types, showing atrophy in the cerebellum, midbrain, and cerebrum.
T2WI and FLAIR hyperintensity
-
CerebrumCerebral white matter
-
CerebellumCerebellar white matter
-
Middle cerebellar peduncle
-
Brainstem
In the late adult type, there is involvement of the cerebellar white matter, cerebellar peduncles, brainstem, and cerebral white matter, with bilateral hyperintensities evident on T2WI and FLAIR sequences.
The early adult type also displays T2WI and FLAIR hyperintensities similar to those observed in the late adult type, but the extent of the lesion is typically more limited.
In contrast, the young adult type does not typically exhibit T2WI and FLAIR hyperintensities in the early stages of the disease. However, as the disease progresses, abnormal signals become evident in the periventricular white matter, eventually resembling the pattern seen in the adult types.
Paravermal sign
-
CerebellumParavermis
Paravermal FLAIR hyperintensity is also thought to be specific sign of Neuronal intranuclear inclusion disease (NIID). However, paravermal sign can also be found in this disease and Fragile X associated tremor-ataxia syndrome (FXTAS).