Creutzfeld-Jakob disease. Subacute sclerosing panencephalitis. Lyme disease (neuroboreeliosis).
Creutzfeldt-Jakob disease
- Neurodegenerative condition; most common subtype of transmissible spongiform encephalopathy (TSE), or prion disease.
- TSEs are all characterized by the deposition of the prion protein (PrP) in the brain.
- Long incubation period, but rapidly progressive and universally fatal.
- Prion diseases should be in the differential diagnosis of any patient presenting with a rapidly progressive dementia.
Etiology
- Prions are infectious particles composed of protein that replicate within the body’s cells even though they possess no genetic material of their own.
- They are proteins that occur normally in neurons of the CNS.
- These proteins, once misfolded, affect signalling processes, damaging neurons and resulting in degeneration.
- The defective protein can be transmitted by contaminated harvested human brain products, corneal grafts, dural grafts, or electrode implants and human growth hormone or they can arise in situ by mutation of the host’s genetic material or reach the body from outside and incorporate themselves into its cells, where they replicate.
Pathogenesis
Several types of CJD
- Familial CJD is an autosomal dominant disorder caused by a mutation in the PRNP gene, which codes for the prion protein cellular isoform (PrPC).
- In sporadic CJD, PrPC undergoes a conformational change to produce an abnormal prion protein (PrPSc). PrPSc then serves as a template on which PrPC is converted to additional PrPSc.
- In iatrogenic CJD, PrPSc is introduced into the brain from an external source.
- Variant CJD, strong evidence links vCJD to mad cow disease i.e. there is bovine-to-human transmission
In each case, the result is accumulation of abnormal prions in brain tissue. The ability of PrPSc to induce the PrPSc conformation in PrPC prions enables it to replicate without nucleic acids.
Clinical findings
- Pathologic hallmarks: generalized brain atrophy, spongiform degeneration (tiny holes in the cortex), and widespread gliosis without inflammation.
- Dementia present, may begin as mild global cognitive impairment or a focal cortical disorder such as aphasia, apraxia, or agnosia. Dementia becomes dominant sign as disease progresses
- Progression to akinetic mutism or coma typically ensues over a period of months.
- Psychiatric symptoms including anxiety, euphoria, depression, labile affect, delusions, hallucinations, and changes in personality or behaviour may be prominent.
- Fever is absent.
- Myoclonus (often induced by a startle), extrapyramidal signs (rigidity, bradykinesia, tremor, dystonia, chorea, or athetosis), cerebellar signs, and pyramidal signs.
- Visual field defects, cranial nerve palsies, and seizures occur less often.