Definition
Creutzfeldt-Jakob disease is a form of human spongiform encephalopathy, which leads to rapidly progressive and fatal dementia.
The pathology depends on the accumulation of a poorly folded and aggregated form of a particular protein, called PrP (prion protein).
PrP is normally found on the outer surface of the plasma membrane, especially of neurons, and has the unfortunate characteristic of being convertible into a very anomalous isoform. This altered conformation, in fact, is not only resistant to proteolysis and tends to accumulate easily, but also demonstrates infectious capacities because it converts normally folded PrP molecules in the same altered form. This property creates a vicious circle that causes the propagation of the abnormal form of PrP and allows it to spread from one cell to another in the brain.
The modified proteins (prions), lead to the progressive loss of neurons and, during the disease, lead to the formation of protein aggregates (amorphous deposits and amyloid plaques) and of microvacuolations of the brain tissue, which takes on a spongy type structure.
Most cases are sporadic; means that Creutzfeldt-Jakob disease appears for the first time in the patient, typically over the age of 40 (on average, affects 60-year-olds), for reasons not yet known.
5-15% of cases, on the other hand, have a family origin. Indeed, Creutzfeldt-Jakob disease can be acquired with autosomal dominant transmission, through a mutation in the gene that codes for the prion protein (PRNP). In the family form, the age of onset is earlier and the clinical course is longer.
There is also an iatrogenic form of Creutzfeldt-Jakob disease, associated with accidental contact with contaminated biological material. The iatrogenic form may appear after particular medical-surgical procedures, after corneal or dural transplantation from cadavers, the use of contaminated neurosurgical instruments and the use of stereotaxic intracerebral electrodes. Another recognized iatrogenic cause is the growth hormone preparation prepared from human pituitary glands, now in disuse thanks to the advent of recombinant technology.
Man can also contract the disease by consuming raw or undercooked parts of animals infected with the variant form of Creutzfeldt-Jakob disease, known as bovine spongiform encephalopathy (or mad cow disease ).
Most common symptoms and signs *
- Aphasia
- Agnosia
- Hallucinations
- Apraxia
- Asthenia
- Ataxia
- Muscular atrophy and paralysis
- Muscular atrophy
- Convulsions
- Korea
- Dementia
- Depression
- Difficulty concentrating
- Language difficulties
- Dysarthria
- Dysphagia
- Temporal and spatial disorientation
- Mood disorders
- Insomnia
- hypokinesia
- myoclonus
- Nystagmus
- Memory loss
- Loss of coordination of movements
- Loss of balance
- Drowsiness
- Confusional state
- Tremors
- Dizziness
- Double vision
- Blurred vision
Further indications
Dementia, ataxia and myoclonus are the most characteristic symptoms of Creutzfeldt-Jakob disease.
After a long, asymptomatic incubation period, the disease presents with dizziness, blurred vision or diplopia, which rapidly worsen over days. In the early stages, memory loss, behavioral changes, irritability, depression, fatigue and sleep disorders appear.
During the intermediate stages of Creutzfeldt-Jakob disease, apathy, confusion, language disorders, postural stiffness, dysfunction of balance and coordination (ataxia) occur. Myoclonus reflex, caused by noise or other sensory stimuli, develops within the first 6 months and remains until advanced Creutzfeldt-Jakob disease. Other CNS deficiencies are manifested by convulsions, visual agnosia, hallucinations and various motor disorders (eg hypokinesia, dystonic postures, choreo-atetosic movements and tremor).
Death usually occurs in 1 or 2 years, due to complications such as pneumonia ab ingestis.
The diagnosis of Creutzfeldt-Jakob disease can be difficult. Magnetic resonance imaging of the brain can show abnormalities in the basal ganglia and cortex, as well as brain atrophy. Cerebrospinal fluid analysis is typically normal, but the characteristic 14-3-3 protein is often identified. The electroencephalogram is atypical and can show characteristic triphasic peaks.
Currently, no effective treatment is available to treat Creutzfeldt-Jakob disease.
