Transmissible Spongiform Encephalopathies (TSEs) or human prion diseases

Transmissible Spongiform Encephalopathies (TSEs) or human prion diseases are rare and incurable neurodegenerative diseases affecting humans and animals. TSEs are caused by a group of non-conventional agents called prions that are resistant to common inactivation or removal procedures, thus causing serious human-to-human transmission problems through medical or surgical procedures. Prion diseases can present in various etiopathogenetic forms: sporadic, iatrogenic, genetic and variant Creutzfeldt-Jakob disease, all linked to the misfolding of the cellular prion protein. 

SPORADIC CREUTZFELDT-JAKOB (CJD) DISEASE 
Sporadic cases are not related to obvious risk factors and comprise approximately 80% of all CJD cases. The diagnosis is CERTAIN only when it is confirmed by the post-mortem neuropathological examination (or in special cases, on material taken through a brain biopsy). Diagnosis is LIKELY if the neuropathological examination has not been performed, but the patient has unequivocal clinical features (rapidly progressive dementia and at least two of the following clinical signs: myoclonus, visual disturbances or cerebellar, pyramidal or extrapyramidal signs, akinetic mutism) and a typical electroencephalographic trace or the identification of the protein 14-3-3 in the cerebrospinal fluid or bilateral signal increase in the basal nuclei or at least in two regions of the cortex (temporal, parietal, occipital) in brain Nuclear Magnetic Resonance images. Diagnosis is also LIKELY in the case of a progressive neurological syndrome and positive RT-QuIC (in vitro amplification of the pathological PrP protein).

IATROGENIC CJD
Iatrogenic cases appear following accidental infection due to medical procedures with contaminated biological material or improperly decontaminated surgical instruments. In Italy, the majority of cases are due to implantation of dura mater during neurosurgery.

GENETIC TSE
Genetic cases are always associated with mutations in the PrP gene (PRNP). To make the diagnosis of genetic TSE it is necessary that among the first degree relatives there is a case of certain / probable TSE or that the patient is a carrier of a mutation in the PRNP gene. There are three forms of genetic TSE: Genetic CJD, with clinical and instrumental characteristics similar to sporadic CJD Gerstmann-Sträussler-Scheinker syndrome (GSS), characterized by progressive ataxia and dementia that usually appears late. The clinical duration of GSS is greater than that of CJD (between 2 and 10 years) Fatal Familial Insomnia (FFI), characterized by insomnia, autonomic nervous system disorders, motor and cognitive disorders 

VARIANT CREUTZFELDT-JAKOB (CJD)
Variant CJD is caused by exposure to the Bovine Spongiform Encephalopathy (BSE) agent. It differs from the sporadic form of CJD by an earlier onset, a longer clinical duration of the disease (greater than 1 year) and characteristic onset symptoms represented by behavioral disturbances, personality changes or depression, sensory disturbances. Most patients develop cerebellar ataxia early, while myoclonus, choreo-athetosis, and dementia appear as the disease progresses. The EEG chart does not present the typical characteristics found in sporadic CJD. Brain MRI and, in some cases, tonsil biopsy are useful for diagnosis. On neuropathological examination, numerous deposits of amyloid plaques are observed surrounded by spongiosis (florid plaques). To date, three cases of vMCJ have been identified in Italy.