3.10.6 Prion diseases
Prion Diseases
Prion diseases, also known as transmissible spongiform encephalopathies, are a group of rare and often fatal neurodegenerative disorders that affect the brain and central nervous system. They are caused by abnormally folded protein particles, called prions, that can spread from one individual to another through contaminated food, medical equipment, or surgical procedures.
The hallmark of prion diseases is the accumulation of abnormal prions in the brain, which can lead to the progressive degradation of brain tissue and the formation of characteristic spongiform changes. These changes are characterized by the presence of vacuoles, or tiny fluid-filled spaces, in the brain, which gives it a spongy appearance.
This is compared to viruses and bacteria which consist of protein, and RNA or DNA. Prion protein is the product of a gene located on chromosome 20 referred to as PRNP. The gene is normally expressed and not unique to just prion diseases. The prion protein expressed in the nervous system is called PrP.
Prion diseases can manifest in a variety of ways, depending on the specific form of the disease and the regions of the brain that are affected. Common symptoms of prion diseases include memory loss, behavioural changes, ataxia (difficulty with coordination and balance), and progressive decline in cognitive function.
Diagnosis of prion diseases is often challenging, as the symptoms can be similar to those of other neurodegenerative disorders. In addition, the incubation period for prion diseases can be quite long, sometimes lasting years or even decades, making early detection difficult.
There is currently no cure for prion diseases, and treatment is primarily focused on managing symptoms and providing supportive care. The neuropathology of prion diseases highlights the importance of research into the underlying mechanisms of these disorders, in order to develop more effective treatments and therapies.
In conclusion, prion diseases are a group of rare and often fatal neurodegenerative disorders that are caused by abnormally folded protein particles, called prions, which can lead to the progressive degradation of brain tissue and characteristic spongiform changes. Further research is needed to better understand the neuropathology of prion diseases and to develop more effective treatments and therapies.
Prion diseases, often known as transmissible spongiform encephalopathies (TSEs), are a group of infrequent, slowly progressing neurodegenerative illnesses that can affect both humans and animals. There is no known cure and treatment is generally a palliative approach. The annual incidence is about 1 in 1,000,000. Long incubation times, distinctive spongiform alterations linked to neuronal death, and an inability to elicit an inflammatory response set them apart.
Three aetiologies are referred to:
| Prion disease aetiology: | Summary: |
| Sporadic | Arise spontaneously with no known cause. |
| Familial | Resulting from genetic mutations in the PrP gene. |
| Variant (transmitted) | Related to bovine spongiform encephalopathy. Transmission of abnormal prion protein via body fluids like faeces, saliva, blood, or urine, through environmental contamination of soil, food or water. |
Puoti, (2012)
It is thought that prions are the cause of TSEs. The name “prions” refers to abnormal, pathogenic organisms that can spread and are capable of causing specific, normal cellular proteins known as prion proteins, which are most prevalent in the brain, to fold abnormally. These typical prion proteins’ roles are yet not fully known. Brain damage and the typical symptoms of the disease are caused by the prion proteins’ aberrant folding. Prion illnesses typically advance quickly.
The definitive diagnosis of prion disease is by histological examination of brain tissue.
Sporadic CJD vs variant CJD:
VariantCJD is a type of transmitted prion disease and is among the rarest of them all. It is felt psychiatrists should be aware of this type as it affects a younger population and often presents with psychiatric symptoms. But the last reported case of vCJD was in 2016.
| Characteristics: | sCJD: | vCJD: |
| The average age of onset | 68 years | 28 years |
| Duration of illness till death | 4-5 months | 12-14 months |
| Clinical presentation | Dementia | Psychiatric and behavioural symptoms |
| MRI ‘Pulvinar Sign’ | Absent | Present in over 75-90% of cases |
| Periodic spikes on EEG | Present (triphasic) | Absent |
| Tonsils | Absent | Tonsillar tissue carries prion protein |
Symptoms:
Prion illnesses have extremely lengthy incubation periods, frequently in the tens of years range. When symptoms start to appear, they sometimes deteriorate quickly.
The following are typical signs of a prion disease:
- Cognitive impairment: problems with judgement, memory, and thinking
- Psychiatric changes: personality alterations include agitation, sadness, and apathy
- Perplexity or fuzziness
- Myoclonic jerks or uncontrollable muscular spasms (myoclonus)
- Cerebellar signs: inability to coordinate (ataxia)
- Difficulty sleeping (insomnia)
- Slurred or difficult-to-understand speech, poor eyesight, or blindness
- Seizures (Jellinger & Korczyn, 2018)
References:
(1) Jellinger, K. A., & Korczyn, A. D. (2018). Are dementia with Lewy bodies and Parkinson’s disease dementia the same disease? BMC medicine, 16(1), 1-16.
(2) Puoti, G., Bizzi, A., Forloni, G., Safar, J.G., Tagliavini, F. and Gambetti, P. (2012). Sporadic human prion diseases: molecular insights and diagnosis. The Lancet Neurology, 11(7), pp.618–628.