Normally, prion proteins are encoded by the PRNP gene and exist in a mostly alpha-helix configuration. They are commonly found in the cell membrane of neurons. They play a function in the uptake of copper, have a protective function against free radicals, and are involved in normal synapse function. Prion disease is caused by a misfolded prion protein that has a predominantly beta-sheet structure. This misfolded protein is resistant to the actions of proteases and can induce conformational changes in normal cellular prion proteins.
When physiological prion changes its composition from alpha helix to predominantly beta sheet, it induces similar changes in other prions. Misfolded prions are resistant to proteases, and their accumulation causes intracellular dysfunction as well as extracellular aggregation (plaques). The subsequent vacuolization without inflammation that occurs from neuronal cell death in the central nervous system gives the tissue a spongiform appearance on histology.
Sporadic type is the most common subtype (accounting for approximately 85%). In sporadic cases, there is no identifiable cause.
The familial type accounts for approximately 10-15% of the cases and it is due to a mutation in the PRNP gene that causes glutamic acid to be replaced by lysine leading to the formation of misfolded prions. In individuals with this type of CJD, there is a need for genetic counseling.
Acquired types account for less than 1% of cases and include variant and iatrogenic. Variant type (vCJD) is due to the consumption of meat from cows or sheep with prions in their muscle tissue. Prions in cows cause spongiform encephalopathy in cows, famously known as mad cow disease.
Iatrogenic type is due to medical procedures with contaminated equipment. This has been reported in corneal transplants and neurosurgery.
CJD may not show up for decades but once symptoms emerge, it progresses rapidly leading to death. Rapidly progressive cognitive impairment leading to dementia and myoclonic jerks are the hallmarks of CJD.
CJD presents with rapidly progressing dementia. It is characterized by memory impairments, deficits in speech, reasoning, and spatiotemporal awareness. After the onset of symptoms, patients with CJD also present with behavioral changes, depression, and other neuropsychiatric symptoms such as visual hallucinations.
Cerebellar compromise leads to ataxia and other extrapyramidal signs such as hypokinesia, bradykinesia, and dystonia. Other cerebellar manifestations include nystagmus.
Myoclonus is brief, shock-like, involuntary muscle twitches. In CJD they are often triggered by a startling stimulus. Startles are reproducible exaggerated responses to trivial stimuli such as loud noises. Other muscular symptoms include muscle weakness. Patients may present with hyperreflexia, Babinski sign, and spasticity.
Magnetic resonance imaging (MRI) findings include hyperintense signals involving the cerebral cortex, the head of the caudate, and the putamen on FLAIR, diffusion-weighted imaging (DWI), and T2-weighted images. Other areas involved include the superior frontal gyrus, superior parietal lobule, cingulate gyrus, and the insula.
If CJD is suspected, a lumbar puncture is performed to evaluate if there are increased levels of 14-3-3 protein in the cerebrospinal fluid (CSF). Elevated 14-3-3 levels in the spinal fluid is a sign of neuronal destruction. The findings in the cerebrospinal fluid analysis include the presence of neuron-specific enolase, S100 protein, and tau protein.
Another finding in CJD is the presence of bi- or triphasic periodic sharp waves with a frequency of 1-2 Hz on electroencephalogram (EEG).
There is no cure for CJD- death usually occurs within one year after the onset of symptoms. Current management is focused on supportive and symptomatic treatment.
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