21st November 2023

Prion Diseases

Most living cells contain RNA or DNA. However, prion has protein as an essential component.

The gene for prion protein is located on chromosome 20 (PrPc). The normal prion protein in healthy individuals is mostly expressed in the CNS. The role of PrPc is not clear, but it could potentially help in promoting neuronal growth and survival, copper binding, and regulating synapses, receptors, and circadian rhythms.

Sometimes, a conformational change in PrPc occurs, and a new protein known as PrPSc is formed. The amino acid sequence of this protein is the same as its healthy form. However, it has more beta sheets and fewer alpha helices.

These abnormal proteins are difficult to break down by the proteases, leading to excessive accumulation and, eventually, neurodegeneration.

Histopathological findings in prion disease is as follows:

• Vacuolation: vacuoles give a spongy appearance to the brain. (Thus, spongiform encephalopathy is another name for prion diseases).
• Dendritic loss.
• Generalised inflammation, gliosis and eventually brain atrophy.
• Poor synaptic neurotransmission.

Animal prion diseases such as scrapie, bovine spongiform encephalopathy, and feline spongiform encephalopathy are infective in aetiology.

Features of sporadic and familial CJD

Presenting signs in decreasing order of prevalence:

• Cognitive impairment and psychiatric changes.
• Cerebellar signs.
• Visual signs.
• Myoclonic jerks.
• Peripheral neuropathy.

Late signs:

• Dementia – This occurs in ALL patients who survive.
• Myoclonus.
• Cerebellar signs.
• Seizures.

Familial Creutzfeldt-Jakob disease

• The most common mutation in familial CJD is in the E200K-129M haplotype. The clinical presentation of this is very similar to the MM1 variant of sporadic CJD.
• Very rapid progression, with an average duration of 5 months.

Sporadic and familial fatal insomnia:

• Marked sleep disturbance.
• Sympathetic overactivity.
• Cognitive impairment.
• Ataxia.

Histopathology shows atrophy of the thalamus with mild involvement of the cortex.

Gertsmann-Straussler-Scheinker syndrome

• P102L and G131V are the most common mutations.
• GSS has a much longer course of illness, with an average duration of 5 years.
• Chronic cerebellar ataxia and pyramidal signs are prominent. Dementia develops much later in life.

Iatrogenic prion disease

• Transplanted dura mater and cadaveric growth hormone are the most common causes.
• Iatrogenic prion disease can also occur after corneal and pituitary grafts.

Investigations for prion diseases

• Post-mortem to establish a definite diagnosis.
• EEG – Periodic complexes in sporadic CJD are commonly seen. These can also be present in other dementias and encephalopathies.
• CSF analysis – Often within the normal range in sporadic CJD patients. Sometimes, proteins such as 14-3-3 can be elevated in response to neuronal injury. The 14-14-3 test is not very sensitive to variant CJD.
• MRI – Cerebral atrophy can be seen in some cases of sporadic CJD. In vCJD, the posterior thalamic abnormality called pulvinar sign is very sensitive and specific.