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.

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 VPSPr 3.

Neuropathologically, VPSPr is characterised 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 VPSPr 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 VPSPr has only a limited potential for human-to-human transmission 4.

Radiographic features are non-specific in VPSPr. In available case series-level evidence, MRI has been reported to demonstrate cerebral atrophy 1-3. Notably, and unlike other prion diseases, patients have not demonstrated any regions of high or abnormal diffusion signal on DWI 1-3.

Currently (as of August 2017), there is no treatment currently available for VPSPr so supportive symptomatic management is recommended 3. 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

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

Neurodegenerative diseases

Neurodegenerative diseases are legion and their classification just as protean. A useful approach is to divide them according to underlying pathological process, although even using this schema, there is much overlap and thus resulting confusion.

Share article

Article information

rID: 55123
Tags: cases, cases
Synonyms or Alternate Spellings:
  • Variably protease sensitive prionopathy (VPSPr)
  • Variably protease-sensitive prionopathy

Support Radiopaedia and see fewer ads

Updating… Please wait.
Loadinganimation

Alert accept

Error Unable to process the form. Check for errors and try again.

Alert accept Thank you for updating your details.