Isolated cortical signal increase on MR imaging as a frequent lesion pattern in sporadic Creutzfeldt-Jakob disease

BACKGROUND AND PURPOSE: Hyperintense basal ganglia on MR imaging support the diagnosis of sporadic Creutzfeldt-Jakob disease (CJD). Our aim was to study the frequency of patients with sporadic CJD presenting with and without characteristic basal ganglia lesions on MR imaging and to examine the corresponding patient characteristics.MATERIALS AND METHODS: Fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted images (DWI) of 55 patients with CJD were assessed for signal-intensity increase (FLAIR) or restricted diffusion (DWI) in 7 cortex regions and the basal ganglia, thalamus, and cerebellum. Patient characteristics as well as electroencephalography, CSF, and codon 129 genotype of the prion protein gene (PRNP) were correlated with the most frequent MR imaging lesion patterns.RESULTS: Two major lesion patterns were identified by DWI: cortex and basal ganglia involvement (two thirds) and isolated cortex involvement (one third). In the latter patient group, the cortex involvement was widespread (at least 3 regions affected in 89% on DWI) and usually included the frontal and parietal lobes (78%). The length of the disease course was significantly prolonged (median, 12 versus 5 months). No significant differences were observed concerning electroencephalography and CSF findings and codon 129 genotype distributions. Of 4 patients with normal MR imaging findings, the CSF was positive for the 14-3-3 protein in 3.CONCLUSION: A high number of patients with CJD present without basal ganglia lesions on MR imaging. Isolated cortex involvement on DWI and FLAIR should lead to suggestion of CJD, even if the disease course is only slowly progressive. Additional 14-3-3 protein analysis in the CSF may support the CJD diagnosis.

Sporadic Creutzfeldt-Jakob disease (CJD) is a rare and fatal disease caused by the accumulation of abnormal/pathologic prion protein (PrP^Sc; Sc indicates scrapie) in the human brain. The classic disease type is characterized by rapidly progressive dementia, ataxia, abnormal muscle tone, and myoclonus. It leads to a state of akinetic mutism and death after a median disease duration of 6 months.¹ The definite CJD diagnosis relies on the finding of PrP^Sc in the brain tissue, together with astrocytic gliosis, nerve cell loss, and spongiform degeneration as the typical neuropathologic changes.^2,3During one''s lifetime, MR imaging hyperintensity of the basal ganglia on T2-weighted (T2WI), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) is increasingly used to support the CJD diagnosis, next to positive CSF (14-3-3 protein) and electroencephalography (EEG) findings of periodic sharp-wave complexes (PSWCs). Although the origin of the signal-intensity changes is still not fully understood, hyperintensity on T2WI and FLAIR has been thought to be caused by gliosis, whereas abnormalities on DWI are most likely derived from spongiform changes.^4–6 DWI was shown to be the most sensitive sequence in the detection of brain lesions, particularly in the neocortex.^7–10 Isolated cortex involvement was also found.^9,11Although abnormal MR imaging findings in CJD have been studied in detail with respect to their location, few attempts have been made to define the most frequently occurring patterns of hyperintensity in a spectrum of patients. Six disease phenotypes (MM1, MM2, MV1, MV2, VV1, and VV2) defined by the codon 129 genotype (MM, MV, VV) of the prion protein gene (PRNP) and pathologic isotype of the PrP^Sc type 1 or 2 have been recently described with distinctive neuropathologic features and various clinical and diagnostic findings.^1–3,12 On MR imaging, predominant cortical (VV1)¹³ or subcortical involvement (MV2 and VV2)^14,15 or no abnormalities (MM2)^16,17 were found in smaller case series.To date, to our knowledge, the overall distribution of MR imaging abnormalities has not been studied in a larger spectrum of patients with CJD, and it is unclear whether there are clinical correlates corresponding to specific MR imaging lesion patterns. The proportion of patients presenting without basal ganglia abnormalities is unknown.We defined the most frequent MR imaging lesion patterns and corresponding clinical characteristics in a CJD patient collective by using highly sensitive MR images, and we considered a possible influence of the codon 129 genotype of the PRNP. We particularly focused on patients lacking basal ganglia abnormalities on MR imaging and suggested criteria that might support the early CJD diagnosis in these patients.