A multimodal neuroimaging study of a case of crossed nonfluent/agrammatic primary progressive aphasia
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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 (18F-FDG PET) and DaT-scan with 123I-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 18F-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.
KeywordsCrossed aphasia Nonfluent/agrammatic primary progressive aphasia (nfvPPA) Functional MRI 18-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) Diffusion tensor tractography Corticobasal syndrome (CBS)
This study was partially supported by a grant from the Italian Ministry of Health (Grant#GR-2010-2303035).
Compliance with the ethical standards
Ethical standard statement
Approval was obtained from the local ethical standards committee on human experimentation and written informed consent from all subjects before enrolment. The study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Conflicts of interest
EG. Spinelli, F. Caso, G. Gambina, G. Magnani, E. Canu, V. Blasi, D. Perani, A. Falini, and M.L. Gorno-Tempini report no disclosures.
F. Agosta serves on the editorial board of the Journal of Neurology; has received speaker honoraria from Biogen Idec and EXCEMED– Excellence in Medical Education; and receives research supports from the Italian Ministry of Health, and AriSLA (Fondazione Italiana di Ricerca per la SLA).
G. Comi has received compensation for consulting services and/or speaking activities from Novartis, Teva Pharmaceutical Ind., Sanofi, Genzyme, Merck Serono, Biogen, Bayer, Actelion, Serono Symposia International Foundation, Almirall, Chugai and Receptos.
M. Filippi is Editor-in-Chief of the Journal of Neurology; serves on scientific advisory boards for Teva Pharmaceutical Industries; has received compensation for consulting services and/or speaking activities from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, and Teva Pharmaceutical Industries; and receives research support from Bayer Schering Pharma, Biogen Idec, Merck Serono, Teva Pharmaceutical Industries, Novartis, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, Alzheimer’s Drug Discovery Foundation (ADDF), the Jacques and Gloria Gossweiler Foundation (Switzerland), and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
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