The clinico-metabolic correlates of language impairment in corticobasal syndrome and progressive supranuclear palsy

Abstract

Purpose: To assess the clinical-metabolic correlates of language impairment in a large sample of patients clinically diagnosed as corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPs). Methods: We included 70 patients fulfilling current criteria for CBS (n = 33) or PSPs (n = 37). All subjects underwent clinical-neuropsychological and FDG-PET assessments at the time of diagnosis. The whole patient's cohort was grouped into three subgroups according to the language characteristics, i.e., (a) nfv-PPA; (b) subtle language impairments, LANG-; (c) no language deficits, NOL-. FDG-PET data were analysed using an optimized voxel-based SPM method at the single-subject and group levels in order to evaluate specific hypometabolic patterns and regional dysfunctional FDG-PET commonalities in subgroups. Results: 21 patients had a nfvPPA diagnosis (i.e., nfv-PPA/CBS = 12 and nfv-PPA/PSPs = 9), while 20 patients had a subtle language impairment LANG- (i.e., CBS = 12 and PSPs = 8), not fulfilling the criteria for a nfv-PPA diagnosis. The remaining sample (i.e., 9/33 CBS and 20/37 PSPs patients) did not show any language deficit. FDG-PET results in individuals with a nfv-PPA diagnosis were consistent with the typical nfv-PPA pattern of hypometabolism (i.e., left fronto-insular and superior medial frontal cortex involvement), both in CBS and PSPs. The LANG-CBS and LANG-PSPs subjects had different FDG-PET hypometabolic patterns involving, respectively, parietal and frontal regions. As expected, NOL-CBS and NOL-PSPs showed a predominant right hemisphere involvement, with selective functional metabolic signatures typical of the two syndromes. Conclusions: Language impairments, fulfilling the nfv-PPA criteria, are associated with both CBS and PSPs clinical presentations early in the disease course. Subtle language deficits may be present in an additional proportion of patients not fulfilling the nfv-PPA criteria. The topography of brain hypometabolism is a major dysfunctional signature of language deficits in CBS and PSPs clinical phenotypes. Keywords: Positron Emission Tomography, FDG-PET, Corticobasal syndrome, Progressive supranuclear palsy, Non-fluent variant of primary progressive aphasia, nfv-PPA