Current clinical diagnosis in Creutzfeldt-Jakob disease: Identification of uncommon variants

Abstract

According to the recently established molecular basis for phenotypic heterogeneity of sporadic Creutzfeldt‐Jakob disease (CJD), six different phenotypes are characterized by the size of the protease‐resistant fragment of the pathological prion protein (types 1 and 2) and homozygosity or heterozygosity for methionine or valine at codon 129 of the prion protein gene (designated by MM1, MM2, MV1, MV2, VV1, and VV2). In the present investigation, we analyzed the value of commonly used clinical tests (electroencephalogram [EEG], detection of 14‐3‐3 protein in cerebrospinal fluid [CSF], and hyperintensity of the basal ganglia in magnetic resonance imaging) for the clinical diagnosis in each CJD phenotype. The detection of periodic sharp and slow wave complexes in the EEG is reliable in the clinical diagnosis of MM1 and MV1 patients only. The CSF analysis for 14‐3‐3 protein showed high sensitivity in all analyzed subgroups with the exception of MV2 patients. Valine‐homozygous patients had a negative EEG, but most had detectable levels of neuronal proteins in the CSF. The sensitivity of the magnetic resonance imaging was 70%, irrespective of the subgroup, but was particularly reliable in the clinical diagnosis of MV2 patients. The widening spectrum of diagnostic techniques in CJD is not only useful in the increased accuracy of the clinical diagnosis but should also lead to the identification of more atypical cases of sporadic CJD. Ann Neurol 2000;48:323–329

MRI and clinical syndrome in dura materrelated Creutzfeldt-Jakob disease

“…In sCJD, six molecular types (codon 129 genotype + PrP Sc type 1 or 2; MM1, MM2, MV1, MV2, VV1, VV2) have been described with various clinical and diagnostic findings [42,43]. Basal ganglia and cortical signal increase are most frequently found on the MRI [44][45][46][47][48].…”

Imaging of prion diseases

“…Unfortunately, this finding has a limited sensitivity of approximately 40-67%, only occur relatively late in the disease course and is mainly positive in the MM1 and MV1 molecular subtypes (8,(29)(30)(31)(32). Older age and shorter disease duration are correlated with increased likelihood of a positive test (33).…”

“…Older age and shorter disease duration are correlated with increased likelihood of a positive test (33). DWI may be positive in the absence of PSWCs (7,8,29). In addition to EEG, multiple CSF markers have been identified; the most frequently cited is the 14-3-3 protein, a marker of neuronal damage.…”

“…The VV1 and MM2-cortical subtypes are notable for prominent cortical involvement, especially the VV1 variant, in which the basal ganglia are almost always spared (31,57). The rare MM2-thalamic subtype, also known as sporadic fatal insomnia (SFI), has been reported to be occult in the few small series available on this extremely rare condition (29,58). Interestingly, the genetic form of the same disease, familial fatal insomnia (FFI), is also occult on conventional imaging (see below).…”

Risikofaktoren der sporadischen Creutzfeldt-Jakob-Krankheit

“…Die Symptomatik der Prionerkrankungen ist sehr heterogen und wird zudem bei der sCJK stark durch den jeweiligen Codon-129-Genotyp und PrP-Subtyp beeinflusst (Parchi et al 1999, Zerr et al 2000c, Meissner et al 2005, Krasnianski et al 2006a und b). Einen Überblick über die führenden klinischen Symptome, die…”