Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech.

Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 subjects with a neurodegenerative speech and language disorder were prospectively recruited and underwent detailed speech and language, neurological, neuropsychological and neuroimaging testing. The neuroimaging battery included 3.0 tesla volumetric head magnetic resonance imaging, [(18)F]-fluorodeoxyglucose and [(11)C] Pittsburg compound B positron emission tomography scanning. Twelve subjects were identified as having apraxia of speech without any signs of aphasia based on a comprehensive battery of language tests; hence, none met criteria for primary progressive aphasia. These subjects with primary progressive apraxia of speech included eight females and four males, with a mean age of onset of 73 years (range: 49-82). There were no specific additional shared patterns of neurological or neuropsychological impairment in the subjects with primary progressive apraxia of speech, but there was individual variability. Some subjects, for example, had mild features of behavioural change, executive dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter revealed focal atrophy of superior lateral premotor cortex and supplementary motor area. Voxel-based morphometry of white matter showed volume loss in these same regions but with extension of loss involving the inferior premotor cortex and body of the corpus callosum. These same areas of white matter loss were observed with diffusion tensor imaging analysis, which also demonstrated reduced fractional anisotropy and increased mean diffusivity of the superior longitudinal fasciculus, particularly the premotor components. Statistical parametric mapping of the [(18)F]-fluorodeoxyglucose positron emission tomography scans revealed focal hypometabolism of superior lateral premotor cortex and supplementary motor area, although there was some variability across subjects noted with CortexID analysis. [(11)C]-Pittsburg compound B positron emission tomography binding was increased in only one of the 12 subjects, although it was unclear whether the increase was actually related to the primary progressive apraxia of speech. A syndrome characterized by progressive pure apraxia of speech clearly exists, with a neuroanatomic correlate of superior lateral premotor and supplementary motor atrophy, making this syndrome distinct from primary progressive aphasia.

Clinical correlates of white matter tract degeneration in progressive supranuclear palsy.

OBJECTIVES: To use diffusion tensor imaging to assess white matter tract degeneration in progressive supranuclear palsy (PSP) and to investigate correlates between tract integrity and clinical measures. DESIGN: Case-control study. SETTING: Tertiary care medical center. PATIENTS/PARTICIPANTS: Twenty patients with probable PSP and 20 age- and sex-matched healthy controls were enrolled. All patients with PSP underwent standardized clinical testing, including the Frontal Behavioral Inventory and Frontal Assessment Battery to assess behavioral change, the PSP Rating Scale to measure disease severity, the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (parts II and III) to measure motor function, and the PSP Saccadic Impairment Scale to measure eye movement abnormalities. METHODS: Fractional anisotropy and mean diffusivity were measured using region of interest analysis and tract-based spatial statistics. RESULTS: Compared with controls, abnormal diffusivity was observed predominantly in the superior cerebellar peduncles, body of the corpus callosum, inferior longitudinal fasciculus, and superior longitudinal fasciculus in patients with PSP. Fractional anisotropy values in the superior cerebellar peduncles correlated with disease severity (r = -0.59, P = .006), inferior longitudinal fasciculus correlated with motor function (r = -0.51, P = .02), and superior longitudinal fasciculus correlated with severity of saccadic impairments (r = -0.45, P = .047). CONCLUSIONS: The results of this study demonstrate that PSP is associated with degeneration of the brainstem, association, and commissural fibers and that this degeneration likely plays an important role in clinical dysfunction.