alpha-synuclein and Aphasia--Primary-Progressive

A 65-year-old man presented with word-finding difficulty and gait disturbance. His speech was nonfluent with word retrieval impairment and difficulties with sentence repetition. Other cognitive domains were intact initially. He developed asymmetrical bradykinesia, rigidity and a rest tremor. Over the following 8 years, his speech production impairment slowly deteriorated with the development of a motor speech disorder, anomia, impaired repetition of single words as well as sentences, and impaired comprehension of initially sentences then single words. His parkinsonian syndrome also deteriorated with limited response to levodopa. Serial brain MRI revealed progressive asymmetric perisylvian atrophy. He died after a disease duration of 12 years. The clinical syndrome is discussed by an expert, the pathology is described, and important clinical points from the case are highlighted.

Topics: Aged; alpha-Synuclein; Amyloid beta-Peptides; Aphasia, Primary Progressive; Brain; Gait Disorders, Neurologic; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Mental Status Schedule; Parkinsonian Disorders; tau Proteins; Writing

Frontotemporal lobar degeneration (FTLD) encompasses a variety of clinicopathologic entities. The antemortem prediction of the underlying pathologic lesions is reputed to be difficult. This study sought to characterize correlations between 1) the different clinical variants of primary progressive language and speech disorders and 2) the pathologic diagnosis.. The latter was available for 18 patients having been prospectively monitored in the Lille Memory Clinic (France) between 1993 and 2008.. The patients were diagnosed with progressive anarthria (n = 5), agrammatic progressive aphasia (n = 6), logopenic progressive aphasia (n = 1), progressive jargon aphasia (n = 2), typical semantic dementia (n = 2), and atypical semantic dementia (n = 2). All patients with progressive anarthria had a tau pathology at postmortem evaluation: progressive supranuclear palsy (n = 2), Pick disease (n = 2), and corticobasal degeneration (n = 1). All patients with agrammatic primary progressive aphasia had TDP-43-positive FTLD (FTLD-TDP). The patients with logopenic progressive aphasia and progressive jargon aphasia had Alzheimer disease. Both cases of typical semantic dementia had FTLD-TDP. The patients with atypical semantic dementia had tau pathologies: argyrophilic grain disease and corticobasal degeneration.. The different anatomic distribution of the pathologic lesions could explain these results: opercular and subcortical regions in tau pathologies with progressive anarthria, the left frontotemporal cortex in TDP-43-positive frontotemporal lobar degeneration (FTLD-TDP) with agrammatic progressive aphasia, the bilateral lateral and anterior temporal cortex in FTLD-TDP or argyrophilic grain disease with semantic dementia, and the left parietotemporal cortex in Alzheimer disease with logopenic progressive aphasia or jargon aphasia. These correlations have to be confirmed in larger series.

Topics: Aged; alpha-Synuclein; Alzheimer Disease; Amyloid beta-Peptides; Aphasia, Primary Progressive; Brain; Brain Mapping; Disease Progression; DNA-Binding Proteins; Female; Frontotemporal Lobar Degeneration; Humans; Language Tests; Male; Middle Aged; Neuropsychological Tests; Postmortem Changes; Predictive Value of Tests; Prions; Prospective Studies; Retrospective Studies; Speech Disorders; Statistics as Topic; tau Proteins; Tomography Scanners, X-Ray Computed; Tomography, Emission-Computed, Single-Photon