Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

Abstract

Several molecular subtypes of sporadic Creutzfeldt–Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt–Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt–Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Patients with sporadic Creutzfeldt–Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt–Jakob disease’ but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt–Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt–Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic resonance imaging was positive in 83% of cases. In all definite cases, the amended criteria would cover the vast majority of suspected cases, being positive in 98%. Cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging are useful in the diagnosis of sporadic Creutzfeldt–Jakob disease. We propose an amendment to the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease to include findings from magnetic resonance imaging scans.

Diagnostic profiles of patients with late-onset Creutzfeldt–Jakob disease differ from those of younger Creutzfeldt–Jakob patients: a historical cohort study using data from the German National Reference Center

“…[7,13]. Whereas a definite diagnosis is restricted to neuropathological examination, in vivo diagnosis of sCJD is based on clinical symptoms, cerebrospinal fluid (CSF) markers, MRI and EEG profiles [15,17]. Six molecular subtypes (MM1, MM2, MV1, MV2, VV1, VV2) of sCJD have been identified [11].…”

Cerebrospinal fluid real‐time quaking‐induced conversion is a robust and reliable test for sporadic creutzfeldt–jakob disease: An international study

“…Current diagnostic criteria for sCJD rely on clinical features, the results of electroencephalography and magnetic resonance imaging, and the presence of 14‐3‐3 protein in the cerebrospinal fluid (CSF) 1, 2. These tests are not specific for CJD, and none is able to detect all forms of CJD 3, 4…”

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).…”

“…However the specificity is relatively low, with multiple false positive results including Hashimoto encephalopathy (36), paraneoplastic encephalopathy (37), herpes encephalitis, cerebrovascular disorders (38), Alzheimer's disease and lymphoma (34) among others. Given the limited accuracy of each tests, a multimodal approach is favored, including the parallel use of EEG, CSF protein 14-3-3 and MRI (31,39). The usefulness of such strategy is depicted in one report including 55 CJD patients: among four patients who had a negative MRI, CSF protein 14-3-3 was found to be positive in three (39).…”