Neuropathological Diagnostic Criteria for Creutzfeldt‐Jakob Disease (CJD) and Other Human Spongiform Encephalopathies (Prion Diseases)

Abstract

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD--sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immunoreactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spongiosis. This includes status spongiosus ("spongiform state"), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of "burnt-out" CJD), "spongy" changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.

Role of Cyclophilin A from Brains of Prion-infected Mice in Stimulation of Cytokine Release by Microglia and Astroglia in Vitro

“…One might expect that the disease-associated PrPres would be capable of stimulating glial cells as deposition of PrPres is usually colocalized with gliosis (10,(43)(44)(45). Furthermore, various in vitro studies have demonstrated microglial activation by the neurotoxic fibrillar form of PrP peptide 106 -126 (14 -17).…”

Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients

“…It causes a rapidly progressive neurodegeneration, ultimately leading to the patient's death within months to few years [27]. To date, a definite diagnosis can only be made by neuropathological examination of brain tissue with immunochemical demonstration of the pathogenic isoform of the prion protein (PrP Sc ) [4]. Clinically, the diagnosis of possible sCJD is made based on neurological findings of rapidly progressive dementia (less than 2 years duration) together with at least two of the following symptoms: myoclonus, ataxia, pyramidal or extrapyramidal signs, akinetic mutism, visual and psychiatric disturbances [26].…”

A rare case of rapidly progressive dementia with elevated RT-QuIC and negative 14-3-3 and tau proteins

“…4 Definite diagnosis of sCJD requires neuropathological or immunochemical detection of the prion protein (PrP-CJD) in brain tissue. 5 PrP-CJD arises through the post-translational conformational conversion of the normal endogenous PrP (PrPC or PrPSen) and accumulates preferentially in nervous tissue. PrP-CJD is also the main component of the infectious CJD agent and propagates itself by seeding or templating the assembly of PrPC into misfolded multimers that can take the form of amyloid fibrils.…”