The evolution of primary progressive apraxia of speech

Abstract

Primary progressive apraxia of speech is a recently described neurodegenerative disorder in which patients present with an isolated apraxia of speech and show focal degeneration of superior premotor cortex. Little is known about how these individuals progress over time, making it difficult to provide prognostic estimates. Thirteen subjects with primary progressive apraxia of speech underwent two serial comprehensive clinical and neuroimaging evaluations 2.4 years apart [median age of onset = 67 years (range: 49-76), seven females]. All underwent detailed speech and language, neurological and neuropsychological assessments, and magnetic resonance imaging, diffusion tensor imaging and (18)F-fluorodeoxyglucose positron emission tomography at both baseline and follow-up. Rates of change of whole brain, ventricle, and midbrain volumes were calculated using the boundary-shift integral and atlas-based parcellation, and rates of regional grey matter atrophy were assessed using tensor-based morphometry. White matter tract degeneration was assessed on diffusion-tensor imaging at each time-point. Patterns of hypometabolism were assessed at the single subject-level. Neuroimaging findings were compared with a cohort of 20 age, gender, and scan-interval matched healthy controls. All subjects developed extrapyramidal signs. In eight subjects the apraxia of speech remained the predominant feature. In the other five there was a striking progression of symptoms that had evolved into a progressive supranuclear palsy-like syndrome; they showed a combination of severe parkinsonism, near mutism, dysphagia with choking, vertical supranuclear gaze palsy or slowing, balance difficulties with falls and urinary incontinence, and one was wheelchair bound. Rates of whole brain atrophy (1.5% per year; controls = 0.4% per year), ventricular expansion (8.0% per year; controls = 3.3% per year) and midbrain atrophy (1.5% per year; controls = 0.1% per year) were elevated (P ≤ 0.001) in all 13, compared to controls. Increased rates of brain atrophy over time were observed throughout the premotor cortex, as well as prefrontal cortex, motor cortex, basal ganglia and midbrain, while white matter tract degeneration spread into the splenium of the corpus callosum and motor cortex white matter. Hypometabolism progressed over time in almost all subjects. These findings demonstrate that some subjects with primary progressive apraxia of speech will rapidly evolve and develop a devastating progressive supranuclear palsy-like syndrome ∼ 5 years after onset, perhaps related to progressive involvement of neocortex, basal ganglia and midbrain. These findings help improve our understanding of primary progressive apraxia of speech and provide some important prognostic guidelines.

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

“…1,14 Other vPSP syndromes named according to their predominant clinical features may account for about one third of earlier presentations in aggregate and include PSP with predominant parkinsonism (PSP-P), 16 pure akinesia with gait freezing (formerly PAGF, now PSP-PGF), 17 corticobasal syndrome (PSP-CBS), 14,18 primary progressive apraxia of speech or non-fluent variant primary progressive aphasia (nfvPPA; when caused by PSP: PSP with predominant speech/language disorder or PSP-SL), 19–21 behavioral variant frontotemporal dementia (bvFTD, when caused by PSP: PSP with predominant frontal presentation or PSP-F), 14,22 and PSP with predominant cerebellar ataxia (PSP-C) (Figure 2). 23 …”

“…28 The MDS PSP criteria recognize a clinical phenotype of PSP initially presenting with predominant speech and language disorder (PSP-SL) features of nfvPPA before developing other motor features of PSP. 19,20 A recent longitudinal study of 13 subjects with primary progressive AOS (PPAOS), which is similar to nfvPPA, found that five subjects developed a syndrome similar to PSP-RS about five years after onset, 19 and 22/25 nfvPPA in a larger series had tau pathology, most commonly 4R tau. 21 Similar to PSP-CBS, the new PSP criteria designate PSP-SL as possible PSP, but probable 4R tauopathy because determining which PSP-SL cases have PSP pathology based on clinical findings is impossible during life.…”

[18F] AV-1451 uptake in corticobasal syndrome: the influence of beta-amyloid and clinical presentation

“…It has also been recognized that subjects can first present with the motor speech disorder, apraxia of speech (AOS) [17, 19] which may then later evolve into CBS. Apraxia of speech is characterized by slow speaking rate, abnormal prosody, distorted sound substitutions, additions, repetitions and prolongations, and syllable segmentation [7, 10], and has been associated with atrophy in the supplementary motor and premotor regions [18].…”

Damage to the Left Precentral Gyrus Is Associated With Apraxia of Speech in Acute Stroke

“…2,3 Today, speech production is not considered as a single function but to comprise multiple distinct processes, including retrieval of verbal symbols, motor speech programming or planning, and end-stage execution of articulation. 4,5 Apraxia of speech (AOS) is the term denoting impairment in motor speech programming/planning, and it is differentiated from aphasia and dysarthria. The clinical characteristics of AOS include slow rate speech, articulatory distortions, articulatory groping, lengthened intersegment duration, and segmentation of syllables.…”