Microglia, amyloid and dementia in Alzheimer disease. A correlative study.

To elucidate the role of microglia in Alzheimer's disease, a clinicopathological study was performed involving 26 cases, the mental status of which had been studied pre mortem by the Blessed test score (BTS). We measured the volume density of CD 68 immunoreactive (IR) microglia, congophilic plaques and Abeta deposits, and the numerical density of neurofibrillary tangles (NFT) in a sample of Area 9 (middle frontal gyrus). Dementia was significantly correlated only with the volume density of Abeta deposits and the numerical density of NFT. The volume densities of microglia and congophilic plaques were strongly correlated. With the intellectual status used as a time scale, IR microglia and amyloid deposits appeared almost simultaneously at an early stage in the pathological cascade and decreased, whereas Abeta and NFT were still accumulating. The intellectual deficit seemed to be more significantly related to the latter two lesions than to the microglia-amyloid complex, that was visible at an earlier stage (around BTS = 15

In Vivo Detection of Thalamic Gliosis: A Pathoradiologic Demonstration in Familial Fatal Insomnia

International audienceBACKGROUND: Increasing evidence supports the usefulness of brain magnetic resonance imaging (MRI) for the diagnosis of human prion diseases. From the neuroradiological point of view, fatal familial insomnia is probably the most challenging to diagnose because brain lesions are mostly confined to the thalamus. OBJECTIVE: To determine whether multisequence MRI of the brain can show thalamic alterations and establish pathoradiologic correlations in a patient with familial fatal insomnia. DESIGN: Radioclinical prospective study. We describe a patient with fatal familial insomnia and normal MRI images. Because the MRI study was performed only 4 days before the patient's death, we were able to compare radiological data with the lesions observed at the neuropathologic level. Patient A 55-year-old man with familial fatal insomnia. Main Outcome Measure Magnetic resonance spectroscopy combined with the measurement of apparent diffusion coefficient of water in different brain areas. RESULTS: The neuroradiological study showed, in the thalamus but not in the other brain regions studied, an increase of apparent diffusion coefficient of water and a metabolic pattern indicating gliosis. These alterations closely correlated with neuropathologic data showing an almost pure gliosis that was restricted to the thalami. CONCLUSION: Considering fatal familial insomnia as a model of thalamic-restricted gliosis, this case demonstrates that multisequences of magnetic resonance can detect prion-induced gliosis in vivo, as confirmed by a neuropathologic examination performed only a few days after radiological examination

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

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

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

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