Variably protease-sensitive prionopathy

Variably protease-sensitive prionopathy (VPSPr) is a very rare type of sporadic human prion disease that was first described in 2008.

Epidemiology

Variably protease-sensitive prionopathy is very rare, with an annual incidence of 1-2 per million ⁵.

Clinical presentation

Clinical presentation is varied, but most patients demonstrate a combination of:

• progressive neuropsychiatric features: dementia and psychosis ^1-3

• progressive motor features: ataxia and parkinsonism ^1-3

• progressive aphasia ^1-3

It is thought that many patients have previously been misdiagnosed as normal pressure hydrocephalus, Parkinson disease, dementia with Lewy bodies, or frontotemporal dementia, due to the overlap with the clinical features of variably protease-sensitive prionopathy ³.

Pathology

Neuropathologically, variably protease-sensitive prionopathy is characterized by spongiform degeneration of the cerebral neocortex, basal ganglia, and thalamus, with relative sparing noted in infratentorial structures ^1-3. Unlike all other sporadic prion diseases which are all associated with prion protein (PrP) that is resistant to treatment with proteases, the PrP in variably protease sensitive prionopathy is somewhat sensitive to these enzymes, making the condition neuropathologically-unique compared to these other prion diseases ^1-3. Furthermore, it has been established that variably protease-sensitive prionopathy has only a limited potential for human-to-human transmission ⁴.

Radiographic features

Radiographic features are non-specific in variably protease-sensitive prionopathy. In available case series-level evidence, MRI has been reported to demonstrate cerebral atrophy ^1-3. Regions of abnormal high diffusion signal (e.g. in the thalamus or cortex) is generally absent ^1-3, but has uncommonly been reported ^6,7.

Treatment and prognosis

There is no treatment available for variably protease-sensitive prionopathy, so supportive symptomatic management is recommended ^3,5. In regards to prognosis, the mean duration of symptoms is reported to be approximately 20 months before death, notably longer than other prion diseases such as Creutzfeldt-Jakob disease ¹. 

History and etymology

The disease was first recognized by Pierluigi Gambetti, an Italian-American neuropathologist and previous director of the National Prion Disease Pathology Surveillance Center, and his colleagues in 2008 ¹.