Variably Protease-sensitive Prionopathy in a Middle-aged Man With Rapidly Progressive Dementia

Variably protease-sensitive prionopathy (VPSPr) is a recently described sporadic prion disease with distinctive clinical and histopathological features. We report the clinical, imaging, and neuropathological features of VPSPr in a 46-year-old right-handed man who presented with progressive cognitive decline, behavior disturbances, and a 50-pound weight loss over 6 months. The initial evaluation revealed severe cognitive impairment with no focal neurologic deficits. His cognitive, psychiatric, and behavior symptoms progressed rapidly, and he died 12 months after the initial visit. Throughout his disease course, workup for rapid progressive dementia was unremarkable except that brain MRI diffusion-weighted imaging showed persistent diffuse cortical and thalamic signal abnormalities. Sporadic Creutzfeldt-Jakob disease was highly suspected; however, two EEGs (8 months apart) demonstrated only nonspecific cerebral dysfunction. The patient's CSF 14-3-3 protein was negative at the initial visit and again 8 months later. His CSF real-time quaking-induced conversion and total tau level were normal. An autopsy of his brain was performed, and the neuropathological findings confirmed VPSPr. Our case underlines the importance of considering VPSPr in the spectrum of prion disease phenotypes when evaluating individuals with rapidly progressive dementia.