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Prion disease — Clinical Guidelines

Overview

Prion diseases, including Creutzfeldt-Jakob disease (CJD), kuru, and Gerstmann-Straüssler-Scheinker syndrome (GSK), are fatal neurodegenerative disorders characterized by the misfolding of prion protein (PrP) into a pathogenic form (PrPTSE) 1 10.

Diagnosis

Clinical Criteria: Rapidly progressive dementia, myoclonus, and characteristic EEG findings 10.

Laboratory Tests: Detection of PrPTSE in cerebrospinal fluid (CSF) or brain tissue via immunohistochemistry 3.

Imaging: MRI may show characteristic spongiform changes 10.

Biopsy: Tonsillar biopsy can detect PrPSc early in preclinical stages of scrapie in sheep 8.

Management

Supportive Care: Focus on symptom management, including sedation for myoclonus and supportive measures for neurological decline 4.

Experimental Therapies: No definitive treatments; research focuses on removing misfolded prion proteins before disease progression 1.

Special Populations

Elderly: Prion diseases predominantly affect older adults, with onset typically in the sixth decade or later 10.

Comorbidities: Management considerations include addressing comorbidities common in elderly patients, though specific guidelines are lacking 4.

Key Recommendations

Early Detection in Sheep: Consider tonsillar biopsy for preclinical diagnosis of scrapie in susceptible sheep genotypes (Evidence: Moderate 8).

Supportive Care Focus: Prioritize comprehensive supportive care to manage symptoms and improve quality of life (Evidence: Expert opinion 4).

Monitoring and Research: Actively monitor for new diagnostic markers and therapeutic approaches targeting prion protein misfolding (Evidence: Weak 3 6).

References

1 Wadman M. Foiling deadly prions. Science (New York, N.Y.) 2024. link 2 Arens W. Comment on Liberski, Gajos, Sikorska, and Lindenbaum: "Kuru, the First Human Prion Disease" . Viruses 2020. link 3 Properzi F, Logozzi M, Abdel-Haq H, Federici C, Lugini L, Azzarito T et al.. Detection of exosomal prions in blood by immunochemistry techniques. The Journal of general virology 2015. link 4 Blakemore S. A suitable case for treatment. Nursing standard (Royal College of Nursing (Great Britain) : 1987) 2009. link 5 Patel SR, Thavaseelan S, Handel LN, Wong A, Sigman M. Bilateral manual externalization of testis with self-castration in patient with prion disease. Urology 2007. link 6 Novitskaya V, Makarava N, Bellon A, Bocharova OV, Bronstein IB, Williamson RA et al.. Probing the conformation of the prion protein within a single amyloid fibril using a novel immunoconformational assay. The Journal of biological chemistry 2006. link 7 Breithaupt H. Mad deer. The North American version of prion disease. EMBO reports 2002. link 8 Schreuder BE, van Keulen LJ, Vromans ME, Langeveld JP, Smits MA. Tonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie. The Veterinary record 1998. link 9 Jeffrey M, Goodsir CM, Bruce ME, McBride PA, Farquhar C. Morphogenesis of amyloid plaques in 87V murine scrapie. Neuropathology and applied neurobiology 1994. link 10 Bendheim PE. The human spongiform encephalopathies. Neurologic clinics 1984. link 11 Diringer H. Sustained viremia in experimental hamster scrapie. Brief report. Archives of virology 1984. link

Prion disease