From the Guidelines
Prion diseases are rare, fatal neurodegenerative disorders caused by abnormally folded proteins called prions, and currently, there is no effective treatment or cure for these diseases, with management focusing on supportive care to alleviate symptoms and improve quality of life 1.
Overview of Prion Diseases
Prion diseases include Creutzfeldt-Jakob disease (CJD), variant CJD, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and kuru. These diseases progress rapidly, with death usually occurring within months to a few years after symptom onset. The underlying pathology involves the conversion of normal prion proteins (PrPC) to an abnormal form (PrPSc) that accumulates in the brain, causing neuronal death and creating a sponge-like appearance in brain tissue.
Diagnosis and Testing
Diagnosis of prion disease is often delayed unless the patient is seen by a neurologist familiar with the disease 1. Historical diagnostic tools have included selected magnetic resonance imaging, electroencephalogram, and nonspecific fluid biomarkers of neuronal damage. The disease-specific real-time quaking induced conversion assay, which detects prion seeds in cerebrospinal fluid or brain tissue, has revolutionized both pre- and postmortem diagnosis, offering >90% sensitivity and specificity, particularly for sporadic forms of prion disease 1.
Management and Treatment
Management of prion diseases focuses on supportive care to alleviate symptoms and improve quality of life. 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 anxiolytics such as lorazepam (0.5-2mg as needed) can address psychiatric symptoms.
- Pain management typically involves standard analgesics.
Prevention
Prevention focuses on avoiding exposure to infected tissue, as prions can be transmitted through:
- Consumption of contaminated meat
- Medical procedures using contaminated instruments
- Rarely through genetic inheritance 1.
Genetic Counseling
Genetic counseling is important for families with a history of prion disease, as approximately 10% to 15% of cases are genetic, arising from autosomal dominant protein-altering variants in PRNP 1. Targeted sequencing of PRNP should be routinely offered for all suspected cases of prion disease, whether or not a family history is immediately apparent 1.
From the Research
Definition and Characteristics of Prion Disease
- Prion diseases are a group of rare, neurodegenerative conditions that are invariably fatal and cause a variety of symptoms, which can prove challenging to control 2.
- The disease-causing agent is a protein (PrP) that is normally produced in the nervous system, aggregated in an abnormal form, known as prion (PrPSc) 3.
- Prion diseases can be acquired sporadically, genetically, or infectiously either by eating meat contaminated with prions or from iatrogenic exposure 3.
Diagnosis and Challenges
- Diagnosing prion disease can be difficult and can lead to frustration 4.
- The use of highly sensitive and specific diagnostic tools, such as MRI and RT-QuIC, may aid in the diagnosis 3.
- Neuropathological examination of brain tissue ensures a definite diagnosis 3.
Treatment and Management
- There is no currently available disease-altering treatment for prion diseases and the care and management of affected patients are directed towards symptomatic relief and quality of life 4.
- Symptomatic treatment follows many of the same principles observed in geriatric and/or hospice care, with some important differences due to disease-specific characteristics 4.
- Pharmacological management of neuropsychiatric and motor symptoms of prion disease may include the use of benzodiazepines, antipsychotic and anticonvulsant medications 2.
- Education and psychosocial support are also very important in managing patients and families affected by the illness 4.
Research and Future Directions
- There continues to be a paucity of good-quality evidence and a need for longitudinal, population-based and standardised research to allow a robust evidence base, which in turn will guide excellent symptom control and end of life care for this group of complex patients 2.
- Treatment trials have not shown improved survival, but therapies may be available soon 5.
- Preliminary studies suggest that lithium mediated inhibition of glycogen synthetase kinase 3 and lithium-induced autophagy may be avenues for further research 6.