Objective:

To report two patients with sporadic, adult-onset ataxia with a rapidly progressive disease course and extra-cerebellar symptoms resembling prion disease.

Background:

Sporadic, adult-onset cerebellar ataxia is a disease with multiple etiologies. Cortical cerebellar atrophy (CCA), idiopathic late-onset cerebellar ataxia and sporadic adult-onset ataxia of unknown etiology have been used to refer to this disorder. These names describe key features of the disease, including degeneration limited to the cerebellar cortex (with or without secondary involvement of inferior olivary nucleus), slowly progressive ataxia and the absence of a clear etiology.

Design/Methods:

We studied two patients with rapidly progressive cerebellar ataxia and dementia. We performed postmortem evaluation of the brain and whole genome sequencing, as well as analysis of AAGGG pentanucleotide repeat expansion in the RFC1.

Results:

Case 1 was a 36-year-old man with a one-year history of ataxia and dementia. Case 2 was a 41-year-old woman with a 16-month history of ataxia and dementia. Extensive studies on autoimmune etiologies and prion disease were negative in both patients. Pathological findings were consistent with CCA, but there were also degenerative changes in the thalamus of both cases. Immunohistochemistry did not show prion protein deposits. Genetic analyses did not reveal any pathogenic variants associated with cerebellar ataxia or pathologic repeat expansion in the RFC1 gene.

Conclusions:

Although the underlying etiology of rapidly progressive CCA is unknown, we propose that the combination of clinical and pathological features of CAA with a short disease course defines a new disease entity, which we refer to as rapidly progressive cerebellar cortical and thalamic degeneration (RPCCAT).