title: Magnetic resonance diagnostic markers in clinically sporadic prion disease: a combined brain magnetic resonance imaging and spectroscopy study.
abstract: The intra vitam diagnosis of prion disease is challenging and a definite diagnosis still requires neuropathological examination in non-familial cases. Magnetic resonance imaging has gained increasing importance in the diagnosis of prion disease. The aim of this study was to compare the usefulness of different magnetic resonance imaging sequences and proton magnetic resonance spectroscopy in the differential diagnosis of patients with rapidly progressive neurological signs compatible with the clinical diagnosis of sporadic prion disease. Twenty-nine consecutive patients with an initial diagnosis of possible or probable sporadic prion disease, on the basis of clinical and electroencephalography features, were recruited. The magnetic resonance protocol included axial fluid-attenuated inversion recovery-T2- and diffusion-weighted images, and proton magnetic resonance spectroscopy of the thalamus, striatum, cerebellum and occipital cortex. Based on the clinical follow-up, genetic studies and neuropathology, the final diagnosis was of prion disease in 14 patients out of 29. The percentage of correctly diagnosed cases was 86% for diffusion-weighted imaging (hyperintensity in the striatum/cerebral cortex), 86% for thalamic N-acetyl-aspartate to creatine ratio (cutoff </=1.21), 90% for thalamic N-acetyl-aspartate to myo-inositol (mI) ratio (cutoff </=1.05) and 86% for cerebral spinal fluid 14-3-3 protein. All the prion disease patients had N-acetyl-aspartate to creatine ratios </=1.21 (100% sensitivity and 100% negative predictive value) and all the non-prion patients had N-acetyl-aspartate to myo-inositol ratios >1.05 (100% specificity and 100% positive predictive value). Univariate logistic regression analysis showed that the combination of thalamic N-acetyl-aspartate to creatine ratio and diffusion-weighted imaging correctly classified 93% of the patients. The combination of thalamic proton magnetic resonance spectroscopy (10 min acquisition duration) and brain diffusion-weighted imaging (2 min acquisition duration) may increase the diagnostic accuracy of the magnetic resonance scan. Both sequences should be routinely included in the clinical work-up of patients with suspected prion disease.
authors.affiliation: MR Spectroscopy Unit, Department of Internal Medicine, Aging and Nephrology, University of Bologna, Azienda Universitario-Ospedaliera di Bologna, Via Massarenti 9, Bologna, Italy. raffaele.lodi@unibo.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Lodi
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Caterina
authors.initials: C
authors.lastname: Tonon
authors.forename: David
authors.initials: D
authors.lastname: Manners
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.forename: Rosaria
authors.initials: R
authors.lastname: Strammiello
authors.forename: Rita
authors.initials: R
authors.lastname: Rinaldi
authors.forename: Claudia
authors.initials: C
authors.lastname: Testa
authors.forename: Emil
authors.initials: E
authors.lastname: Malucelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Mostacci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rizzo
authors.forename: Giulia
authors.initials: G
authors.lastname: Pierangeli
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Montagna
authors.forename: Bruno
authors.initials: B
authors.lastname: Barbiroli
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D017096:Prion Diseases / Q000175:diagnosis / Q000473:pathology*; D000072002:Prion Proteins; D011328:Prions / Q000737:chemistry
chemical_list: D048948:14-3-3 Proteins; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions