title: A multimodal neuroimaging study of a case of crossed nonfluent/agrammatic primary progressive aphasia.
abstract: Crossed aphasia has been reported mainly as post-stroke aphasia resulting from brain damage ipsilateral to the dominant right hand. Here, we described a case of a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and neuroimaging data for four consecutive years from a 55-year-old right-handed lady (JV) presenting with speech disturbances. 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) and DaT-scan with (123)I-Ioflupane were obtained. Functional MRI (fMRI) during a verb naming task was acquired to characterize patterns of language lateralization. Diffusion tensor MRI was used to evaluate white matter damage within the language network. At onset, JV presented with prominent speech output impairment and right frontal atrophy. After 3 years, language deficits worsened, with the occurrence of a mild agrammatism. The patient also developed a left-sided mild extrapyramidal bradykinetic-rigid syndrome. The clinical picture was suggestive of nfvPPA with mild left-sided extrapyramidal syndrome. At this time, voxel-wise SPM analyses of (18)F-FDG PET and structural MRI showed right greater than left frontal hypometabolism and damage, which included the Broca's area. DaT-scan showed a reduced uptake in the right striatum. FMRI during naming task demonstrated bilateral language activations, and tractography showed right superior longitudinal fasciculus (SLF) involvement. Over the following year, JV became mute and developed frank left-sided motor signs and symptoms, evolving into a CBS clinical picture. Brain atrophy worsened in frontal areas bilaterally, and extended to temporo-parietal regions, still with a right-sided asymmetry. Tractography showed an extension of damage to the left SLF and right inferior longitudinal fasciculus. We report a case of crossed nfvPPA followed longitudinally and studied with advanced neuroimaging techniques. The results highlight a complex interaction between individual premorbid developmental differences and the clinical phenotype.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, 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: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Caso
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.affiliation: SSO Centro Alzheimer e Disturbi Cognitivi, DAI di Neuroscienze, UOC di Neurologia d.O., Azienda Ospedaliera Integrata Verona, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gambina
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, 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, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Canu
authors.affiliation: Department of Neuroradiology and CERMAC, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Blasi
authors.affiliation: Nuclear Medicine Unit, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Perani
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, 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: Department of Neuroradiology and CERMAC, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Memory and Aging Center, University of California, San Francisco, CA, USA.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it.|Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. filippi.massimo@hsr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D001039:Aphasia, Broca / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D057178:Primary Progressive Nonfluent Aphasia / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology
keywords: 18-Fluorodeoxyglucose positron emission tomography (18F-FDG PET); Corticobasal syndrome (CBS); Crossed aphasia; Diffusion tensor tractography; Functional MRI; Nonfluent/agrammatic primary progressive aphasia (nfvPPA)