From the Guidelines
Prion diseases are rare, fatal neurodegenerative disorders caused by abnormally folded proteins called prions, and management focuses on supportive care to alleviate symptoms and improve quality of life. These diseases include Creutzfeldt-Jakob disease (CJD), variant CJD, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and kuru. Currently, there is no effective treatment or cure for prion diseases. Medications such as clonazepam (0.5-2mg daily) or sodium valproate (starting at 250mg twice daily, increasing as needed) may help control myoclonus (muscle jerking) 1. Antidepressants like sertraline (50-200mg daily) or mirtazapine (15-45mg daily) can address depression, while antipsychotics such as quetiapine (25-200mg daily) may help with hallucinations or agitation. Pain management with opioids may be necessary in advanced stages.
Key Points
- Prion diseases progress rapidly, with death typically occurring within months to a few years after symptom onset 1.
- The underlying mechanism involves the conversion of normal prion proteins (PrPc) into an abnormal form (PrPSc) that accumulates in the brain, causing neuronal death and creating a sponge-like appearance in brain tissue.
- Prevention focuses on avoiding exposure to infected tissue, as these diseases can be acquired through consumption of contaminated meat, medical procedures using contaminated instruments, or inherited through genetic mutations 1.
- Genetic counseling is essential for families with a history of prion disease, as 10% to 15% of cases are caused by autosomal dominant gain-of-function variants in the prion protein gene, PRNP 1.
- A detailed pedigree should be taken, noting cause and age of death, disease duration, and neurologic and psychiatric history in at least 3 generations, to personalize the educational part of the genetic counseling session 1.
Transmission and Prevention
- Prion disease is not acquired through any normal activity, including sharing a household, intimate contact, caretaking activities, or routine medical or dental care 1.
- Individuals with pathogenic PRNP variants are healthy for the vast majority of their lives, with prions appearing in the central nervous system only briefly before onset of clinical symptoms.
- Blood-based transmission of prion disease has not been reported for any form of human prion disease other than acquired variant CJD, and even at the symptomatic stage of disease, blood is considered a “no detectable infectivity” tissue by the World Health Organization.
Phenotypes and PRNP Variants
- Symptoms of genetic prion disease vary widely and are imperfectly predicted by PRNP variant, with some variants presenting with a CJD-like phenotype and others with a GSS-like phenotype 1.
- Rare nonsense variants can cause prion disease by producing a truncated version of the protein that fails to properly localize to the plasma membrane, often presenting with a longer disease course and highly variable range of phenotypes atypical of prion disease.
From the Research
Definition and Forms of Prion Disease
- Prion diseases are a group of neurodegenerative diseases caused by abnormally shaped proteins called prions 2, 3, 4, 5.
- These diseases can occur in sporadic, genetic, and acquired forms 2, 3, 4, 5.
- Acquired prion diseases are the least common and are caused by infectious transmission, either by eating meat contaminated with prions or from iatrogenic exposure 2, 3, 4.
Diagnosis and Diagnostic Methods
- The diagnosis of prion diseases is often challenging and may require the use of highly sensitive and specific diagnostic tools, such as MRI and RT-QuIC 3, 4.
- Neuropathological examination of brain tissue ensures a definite diagnosis 3.
- New antemortem potential diagnostic tests based on amplifying prions in order to detect them are showing very high specificity 4.
Treatment and Prognosis
- Unfortunately, to date, all human prion disease clinical trials have failed to show survival benefit 4, 6.
- Despite several clinical trials, no effective treatment has been discovered in humans 6.
- However, an early diagnosis is of paramount importance for patient care decision planning, infection control purposes, and genetic counseling 3.
- Certain infection control protocols should be applied when handling central nervous system and other high-risk tissues 2.