Prion diseases, also known as transmissible spongiform encephalopathies, include kuru in New Guinea; sporadic Creutzfeldt-Jakob disease (sCJD), which is found worldwide; familial CJD (fCJD); and variant CJD (vCJD), which is found mostly in the United Kingdom and France. Variant CJD has been linked to bovine spongiform encephalopathy (“mad cow” disease), which is a prion disease in cattle. Other rare types of prion diseases include fatal insomnia (a rare hereditary disorder that causes difficulty sleeping) and Gerstmann-Sträussler-Scheinker syndrome (an extremely rare disorder that typically occurs around age 40).
Prions are infectious agents formed by the conversion of a normal cell surface protein (PrPC) to a misfolded cell surface protein called PrPCJD or PrPSC (“SC” stands for the animal prion disease scrapie). sCJD may result from somatic mutation in the prion protein gene or, more likely, from the spontaneous, random conversion of a normal prion protein to an abnormal prion protein and the subsequent expansion of the altered form. About 10% of CJD cases are familial, resulting from inherited mutations in the PrP gene.
CJD is uniformly fatal, presenting as a rapidly progressive dementia culminating in death, usually within 8 months. The most commonly reported visual manifestations include diplopia, supranuclear palsies, complex visual disturbances, homonymous visual field defects, hallucinations, and cortical blindness. In the Heidenhain variant of CJD, patients present primarily with isolated visual symptoms. Due to the complex clinical manifestations, this rare but clinically distinct group of patients with sCJD may be a diagnostic dilemma. Diffusion-weighted and FLAIR MRI may reveal early cortical changes and PET scan may reveal hypometabolism in posterior cortical regions.
Diagnostic testing for prion disease includes MRI, electroencephalogram (EEG), lumbar puncture, and possibly brain biopsy. Diffusion-weighted MRI images show typical high-intensity caudate and/or putamen lesions. The EEG shows characteristic periodic sharp wave complexes. CSF usually contains the 14-3-3 protein, and brain histologic studies reveal spongiform degeneration. No treatment is currently available.
Geschwind MD. Prion diseases. Continuum (Minneap Minn). 2015;21(6):1612–1638.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.