The human prion diseases (HPD) are a group of fatal, progressive neurodegenerative disorders occurring in inherited, acquired, and sporadic forms. All of them involve modification of the prion protein (PrP).
Familial forms (caused by inherited mutations in the PrP encoding gene) are rare and include familial Creutzfeldt–Jakob disease (CJD), Gerstmann–Straussler disease (GSD), and fatal familial insomnia (FFI).
Acquired prion diseases include variant CJD, iatrogenic CJD, and kuru. The sporadic forms include the sporadic CJD and the more rare sporadic fatal insomnia. The brain damage observed in HPD is generally characterized by spongiform changes, neuronal damage and loss, astrocytosis, and amyloid plaque formation. This causes severe impairment of brain functions in all disorders (e.g. memory and personality changes as well as psychiatric, movement, and sleep disorders). This inexorably worsens over time, leading to death after a period of severe dementia with inability to move and speak.
At present, the definitive diagnosis of HPD is made through brain biopsy (tonsil biopsy is also useful in the variant CJD). However, in the appropriate clinical context, the characteristic periodic EEG (in sporadic CJD) and/or the positive CSF 14–3–3 protein assay can allow a probable diagnosis. Historically, imaging features are not part of the diagnostic criteria for HPD. There is, however, growing support for MRI to be included in the diagnostic workup. In this regard, MRI plays an extremely important role in early diagnosis, especially with DWI and FLAIR images, which are undoubtedly the most sensitive for the depiction of prion-induced brain lesions. The lesions are characteristically shown as ribbons of cortical hyperintensity, or basal ganglia or thalamic hyperintensity. The cortical and deep lesions may appear alone or together, and although usually bilateral and symmetric, they may be asymmetric or purely unilateral. When these MRI findings are observed in an appropriate clinical context, the diagnosis of HPD is very likely.

1H-MRS

This examination is not included in the diagnostic work-up of HPD and its use in these diseases is presently limited to research studies. However, the use of 1H-MRS could be very useful at early disease stages to follow-up, through the assessment of brain NAA levels, the progression of neuronal loss. Several studies have found significant increases in mI and decreases in NAA in the gray matter of HPD patients, related to the pronounced gliosis and neuronal damage. In basal ganglia, these changes are pronounced from early stages, making 1H-MRS very useful for longitudinal assessment of disease evolution or potential treatments. Since the gray matter quantification of both mI and NAA is important, short TE (30–35 ms) acquisitions are preferred in the basal ganglia and neocortical regions.