Magnetic Resonance Imaging in the diagnosis of Creutzfeldt-Jakob disease

The diagnosis of Creutzfeldt-Jakob disease (CJD) is dependent on an assessment of clinical features together with specialist investigations including electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain and the cerebrospinal fluid (CSF) tests 14-3-3 immunoassay and real-time quaking induced conversion (RT-QuIC). There has been an evolution in the diagnosis of CJD with time as new tests have been developed and this includes MRI, which has proved very useful in the diagnosis of all forms of CJD, including sporadic CJD (sCJD) and variant CJD (vCJD). MRI signal abnormalities in sCJD have a relatively high diagnostic sensitivity and specificity, although this varies in different studies in relation to the precise details of the study population. The primary aim of this thesis: To examine the overall role of MRI brain scan in the diagnosis of sCJD. Other, specific, aims: -How accurate is local reporting of the MRI findings in CJD and has this changed with time? -Is there variation in the utility of MRI in the diagnosis of CJD according to codon 129 genotype and prion protein isotype -Is there evidence that MRI in sCJD and vCJD is more likely to show characteristic features at different stages of the clinical illness and what is the role of serial scans? -Is there a relationship between specific MRI appearances and the clinical presentation in sCJD? -Is the MRI of use in identifying cases of methionine-valine (MV) vCJD? -Are there scans in non-CJD cases that show features suggestive or characteristic of CJD, and are these cases distinguishable from true cases on the basis of clinical features or other investigations? -Are there cases of CJD in which the scans show no characteristic features, and are there any parameters that distinguish these cases, for example scan quality or timing? In order to assess the study aims, 462 cases of sCJD referred the National CJD Research and Surveillance Unit (NCJDRSU), identified as having an MRI brains scan performed during their illness, were analysed retrospectively (2010-2015). 54 non-CJD cases (referred to NCJDRSU, with an initial suspicion of CJD, but who turned out to have other illnesses) were included for comparative analyses (2010-2015). In addition, 25 cases of vCJD with brain MRI DWI sequences (1999-2015) were identified and these scans were analysed. The scans were reviewed by a single Neuroradiologist, experienced in the assessment of MRI, for the presence or absence of features associated with these diseases. The Neuroradiologist was aware of the suspicion of CJD but was blinded to the specific diagnosis in each case. This thesis determines the role of MRI brain scan in the diagnosis of sCJD and provides further validation of the current European diagnostic criteria (2017) for the condition. The results show that brain MRI, with the inclusion of DWI sequences, is a highly sensitive, specific and reliable test for the diagnosis of sCJD if applied in the appropriate clinical circumstances and can improve the diagnostic classification of sCJD in life.