Prion Disease- Pathogenesis, Diagnosis and Management

Intriguing tales of prions diseases, which are defined by infectious particles free of nucleic acid, can be found in historical cases like Kuru and Scrapie. 

Kuru

The Fore people of Papua New Guinea performed ceremonial cannibalism, which is largely to blame for the last known instances of Kuru in 1950 that are still mentioned in medical texts. Eating the brains of departed family members revealed the possibility of prion particle transmission between humans, upending accepted scientific beliefs.

Scrapie

Alternatively, Scrapie sheds light on prion illnesses that primarily afflict sheep and goats. Scrapie's existence, which was discovered more than 200 years ago, highlights how versatile prions may be in other animals and raises questions regarding possible human transmission. Even with their different backgrounds, Kuru and Scrapie both provide insightful information about the transmissibility and cross-species nature of prion diseases, which directs further research into these mysterious illnesses.

Mad Cow Disease

Because of the possibility of zoonotic transmission, mad cow disease, also known as bovine spongiform encephalopathy, or BSE, has written a dark chapter in public health. The main way that the disease is spread is by eating contaminated beef, which highlights the significance of humanely culling affected livestock. Prion particles enter the body through the gastrointestinal tract, pass through the blood-brain barrier, and enter neurons, where they cause significant damage to the neurons. 

Within a year, the patient passes away from dementia, myoclonic convulsions, and a vegetative state due to the rapid progression of symptoms. Although not very effective, Mad Cow Disease can spread between species; examples of animal-to-human transmission as well as human-to-human transmission have been reported, especially among North American deer hunters.

The PRPN gene on chromosome 20 has been found to be a genetic component that contributes to susceptibility in the infectious and genetic etiology of mad cow disease. When prion particles attach to the normal cellular prion protein (PrPc), they cause a conformational change in proteins that causes the disease-causing isoform (PrPsc) to become self-propagative. 

The creation of a beta helix contaminates nearby proteins, starting a series of conformational alterations in neurons. The precise effect on neighboring neurons is still unknown, but the results show up as myoclonic jerks, dementia, and neurodegeneration.

Beyond Mad Cow Disease, the range of prion illnesses includes both the classical form of Creutzfeldt-Jakob Disease (CJD) and its iatrogenic variation. In the 1980s, there were many iatrogenic cases linked to medical procedures including cadaveric pituitary growth hormone injections and corneal transplantation

Latrogenic / Classical CJD 

Latrogenic: Those who had corneal transplant surgery. A recipient of pituitary growth hormone from cadavers. DNA recombinant technology is used to accomplish it these days. A cadaveric pituitary was utilized for hypopituitarism in the 1980s. Injections of human growth hormone were given to patients. In the end, they experienced neurodegeneration.

They began exhibiting signs of fast-onset dementia within a year.

Prion exposure has devastating effects that make it imperative to continue researching these diseases to understand their causes and develop effective defenses.Harrison documented 238 instances of prion illness in 2021.

Neuropathology

Brain biopsies in prion illnesses, especially Variant Creutzfeldt-Jakob Disease (VCJD), show characteristic neuropathological traits. Under high power magnification, floral plaques are indicative of VCJD, which may be associated with the ingestion of low-quality beef. Myoclonic jerks, aberrant firing, and eventual neuronal death are caused by the beta helix isoform of PrPsc appearing in the cytoplasm of neurons, spongiform degeneration, and neuronal loss. Astrocytosis gliosis and the presence of amyloid plaques, which are indicative of Alzheimer's disease and cerebral amyloid angiopathy, are further pathological markers.

Prodromal Symptoms

Include exhaustion, headaches, weight loss, insomnia, anxiety, and visual hallucinations. Prodromal symptoms eventually lead to melancholy, feelings of worthlessness, guilt, and rapid-onset dementia. The various presentations of VCJD include isolated visual impairment (Heidenhain variants), cerebellar/coordination abnormalities (Brownell Oppenheim variants), and extrapyramidal syndrome affecting the basal ganglia, subcortical areas, and the cerebellum. In more advanced phases, startle myoclonus—caused by bright lights or loud noises—permanently occurs throughout sleep.

A confluence of dementia with myoclonus, akin to Alzheimer's disease, dementia with Lewy bodies, corticobasal syndrome, and even ailments such as cryptococcal encephalitis is caused by the unrelenting proliferation of prion particles within the brain. In addition to symptoms of dementia and myoclonus, certain EEG findings, such as periodic electrical bursts and acute wave complexes, are diagnostic features of sporadic Creutzfeldt-Jakob disease (SCJD). The illness usually strikes people 60 years of age or older; symptoms may not include a fever, but they may include elevated CSF pleocytosis and ESR.

Differential diagnosis 

Involves separating prion disorders from other ailments such as frontotemporal dementia, progressive supranuclear gaze palsy (which shows atrophy of the peri-Rolandic area on MRI), dementia with Lewy body, and others. Comprehensive assessments, including imaging scans, antibody testing, and cerebrospinal fluid analyses, are necessary for Hashimoto encephalopathy, limbic encephalitis, neurosyphilis, and uremic or hepatic encephalopathy. The complex neuropathological characteristics and diagnostic difficulties associated with prion diseases highlight the necessity of thorough evaluations to distinguish these illnesses from other neurodegenerative illnesses.

Diagnosis

Prion diseases requires a multimodal approach to workup. One test that stands out as the gold standard and provides accurate results is conformation-dependent immunoassay. But the intrusive character of brain biopsy samples—more especially, the way PrPsc is proteolyzed into fragments of PRP 27–30—offers important insights into the pathophysiology of the illness. Imaging techniques that highlight characteristic features like cortical ribboning and hyperintensities in the basal ganglia, including MRI with flair/DW sequences, are essential in verifying the diagnosis of prion disorders.

Chromosome 20 should be the primary focus of genetic study employing PRPN gene sequencing, especially when there are family connections. Additional diagnostic markers can be obtained by analyzing cerebrospinal fluid (CSF), where neuron-specific enolase and stress protein 14.3.3 are assessed. These CSF markers do, however, show lower sensitivity and specificity, highlighting the significance of combining several diagnostic instruments for a thorough assessment.

Electroencephalography (EEG) is a valuable tool for identifying patterns linked to prion disorders. Identifying features include polyphasic acute discharges that occur every 1 to 2 seconds and repetitive high-voltage triphasic waves with bursts lasting fewer than 200 milliseconds. Furthermore, triphasic wave-like EEG patterns are linked to metabolic encephalopathy, which is frequently observed in illnesses like renal and hepatic failure.

Also Read: Neuromyelitis Optica: Revealing the Mystery 

Symptomatic Management

Prescription drugs may be used to treat particular symptoms including pain, depression, and anxiety. Myoclonus and seizures can be managed with antiepileptic medications.

Assistive Healthcare:

To manage complications, patients with prion illnesses frequently need intensive supportive care. Given that chronic illnesses can cause weight loss and swallowing difficulties, nutritional supplementation is essential. 

Hospice Care: 

Palliative care is necessary to enhance patients' quality of life and support their families because prion diseases are deadly and worsen over time.

Hope you found this blog helpful for your NEET SS Medicine Neurology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.