Early diagnosis of human TSE by multimodality MRI: Spectroscopic detection of thalamic gliosis in a patient with FFI and normal FLAIR and diffusion-weighted imaging

Abstract

International audienceRecently, several reports underlined the usefulness of brain MRI for the diagnosis ofCreutzfeldt-Jakob dis ease. FLAIR sequence and diffusion-weighted imaging (DWI) areconsidered as high sensitive sequences to detect signal alteration of the cortex and thedeep grey matter. Recent advances in therapeutic approach of patients with prion diseaseshave emphasized the need for earlier diagnostic markers that would authorize the onset oftreatment before massive and irreversible lesions of the brain have occurred.Consequently, we designed a radio -clinical study using a multimodality MRIstandardized procedure that aimed to estimate differential sensitivity of FLAIR, DWI andMR spectroscopy for the diagnosis of human TSE. Here we report a case of familial fatalinsomnia with the D178N-129M mutation. FLAIR and diffusion-weighted sequenceswere normal in the whole brain notably in both thalami. However, spectroscopic studyshowed a striking increase of the peak of myo-inositol (mI) and of the mI/NAA ratio inthe thalamus when compared to the other studied brain regions of the patient (frontalisocortex, lenticular nucleus and cerebellar vermis) and to the thalami of control cases (n= 10). This metabolite pattern is indicating of gliosis. Because the MRI study wasperformed only two days before death, we were able to strictly correlate the spectroscopicdata with the neuropathological lesions (including the severity of astrogliosis andmicroglial activation) observed in the thalamus. From this observation, we can concludethat 1) MR spectroscopy can detect prion-related lesions even when other sequencesappear normal 2) spectroscopic metabolite pattern well correlates with theneuropathological one