title: Clinical and MRI correlates of disease progression in a case of nonfluent/agrammatic variant of primary progressive aphasia due to progranulin (GRN) Cys157LysfsX97 mutation.
abstract: Little is known about the longitudinal changes of brain damage in patients with sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) and in progranulin (GRN) mutation carriers. This study reports the clinical and MRI longitudinal data of a patient with nfvPPA carrying GRN Cys157LysfsX97 mutation (GRN+). Voxel-based morphometry, tensor-based morphometry and diffusion tensor MRI were applied to evaluate gray matter (GM) and white matter (WM) changes over three years. The prominent clinical feature was motor speech impairment associated with only mild agrammatism. MRI demonstrated a progressive and severe GM atrophy of inferior fronto-insular-temporo-parietal regions with focal damage to frontotemporal and frontoparietal WM connections. This is the first report of longitudinal MRI data in a nfvPPA- GRN+ patient and this report offers new insights into the pathophysiology of the disease.
authors.affiliation: Neuroimaging Research Unit, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Caso
authors.affiliation: Neuroimaging Research Unit, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.affiliation: Department of Neurology, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magnani
authors.affiliation: Neuroimaging Research Unit, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Galantucci
authors.affiliation: Neuroimaging Research Unit, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Edoardo G
authors.initials: EG
authors.lastname: Spinelli
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.affiliation: Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Department of Neurology, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Neuroimaging Research Unit, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. Electronic address: filippi.massimo@hsr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D001284:Atrophy / Q000473:pathology; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation; D059906:Neuroimaging; D057178:Primary Progressive Nonfluent Aphasia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D000077153:Progranulins; D066127:White Matter / Q000473:pathology
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: Diffusion tensor MRI; Nonfluent/agrammatic variant of primary progressive aphasia; Progranulin; Tensor-based morphometry; Voxel-based morphometry; White matter damage