The evolution of parkinsonism in primary progressive apraxia of speech: A 6-year longitudinal study.
Ontology highlight
ABSTRACT: Introduction
Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome in which patients present with an isolated motor speech disorder. Some PPAOS patients develop parkinsonism and other features of progressive supranuclear palsy (PSP) and/or corticobasal syndrome (CBS) over time. We aimed to assess the evolution of parkinsonian characteristics in PPAOS patients who had been followed yearly for at least six years.Methods
From a large cohort of 46 PPAOS patients, eight were followed yearly for > 6-years in multiple NIH-funded grants. Parkinsonian and other features, including bradykinesia, tremor, rigidity, postural instability, apraxia, ocular motor function and cognition were assessed at each visit, and research criteria applied for PSP and CBS diagnosis. Neurological, speech-language test scores, and [18F]fluorodeoxyglucose PET (FDG-PET) and MRI midbrain volumes were assessed.Results
A Parkinson's plus syndrome developed in all eight patients (100%). Bradykinesia was the earliest feature, followed by rigidity and postural instability. Tremor was not a significant feature. Parkinsonism, limb apraxia and ocular motor impairment tended to develop four-to-five years after onset with some patients having slight asymmetric parkinsonism. Six patients (75%) met research criteria for probable PSP, although only one for PSP-Richardson's syndrome; three patients met criteria for possible CBS. Slightly asymmetric, left-sided, hypometabolism was observed on FDG-PET, not matching asymmetry of Parkinsonism. Midbrain hypometabolism was absent-minimal. Three patients had progressive midbrain volumes in the PSP-Richardson's syndrome range.Conclusions
A Parkinson's plus syndrome may inevitably develop in PPAOS supporting PPAOS as an early presentation of a Parkinson's plus disorder.
SUBMITTER: Seckin ZI
PROVIDER: S-EPMC7769910 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Purpose Individuals with primary progressive apraxia of speech (PPAOS) have apraxia of speech (AOS) in which disruptions in articulation or prosody predominate the speech pattern, referred to, respectively, as phonetic or prosodic subtypes. Many develop aphasia and/or dysarthria. Past research has demonstrated that simple temporal acoustic measures are sensitive to the presence of AOS. The aim of this study was to describe the change in temporal acoustic measures over time and assess if specific patterns of AOS or co-occurring aphasia or dysarthria impact the rate of change over time. Method Durations for multiple productions of the words cat, catnip, catapult, and catastrophe, in an imitative speech task, were recorded for 73 patients, with two to six visits each. A linear mixed-effects model was used to assess the cross-sectional differences and longitudinal influence of AOS subtype and presence of aphasia/dysarthria on speech rate. Pearson correlations were calculated between rate measures and performance on other clinical measures. Results Cross-sectionally, patients with prosodic-predominant PPAOS produced words more slowly than those with phonetic-predominant PPAOS. Patients with either aphasia or dysarthria produced words more slowly than those without. Longitudinally, the speech rate of patients with phonetic-predominant PPAOS had a reduction of 0.5 syllables per second per year. Patients with prosodic-predominant AOS changed less quickly, as did those who developed aphasia. Dysarthria did not impact rate of change. There were strong associations between speech rate measures and other clinical indices of speech and language functioning. Conclusion Simple temporal acoustic measures may reflect the subtype of AOS (phonetic or prosodic predominant), serve as an index of progression of AOS, and inform prognostication relative to the presenting combination of speech and language features. Supplemental Material https://doi.org/10.23641/asha.13564724.
| S-EPMC8632475 | biostudies-literature
Project description:ObjectiveThe goal of this study was to explore the prevalence of nonverbal oral apraxia (NVOA), its association with other forms of apraxia, and associated imaging findings in patients with primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS).MethodsPatients with a degenerative speech or language disorder were prospectively recruited and diagnosed with a subtype of PPA or with PAOS. All patients had comprehensive speech and language examinations. Voxel-based morphometry was performed to determine whether atrophy of a specific region correlated with the presence of NVOA.ResultsEighty-nine patients were identified, of which 34 had PAOS, 9 had agrammatic PPA, 41 had logopenic aphasia, and 5 had semantic dementia. NVOA was very common among patients with PAOS but was found in patients with PPA as well. Several patients exhibited only one of NVOA or apraxia of speech. Among patients with apraxia of speech, the severity of the apraxia of speech was predictive of NVOA, whereas ideomotor apraxia severity was predictive of the presence of NVOA in those without apraxia of speech. Bilateral atrophy of the prefrontal cortex anterior to the premotor area and supplementary motor area was associated with NVOA.ConclusionsApraxia of speech, NVOA, and ideomotor apraxia are at least partially separable disorders. The association of NVOA and apraxia of speech likely results from the proximity of the area reported here and the premotor area, which has been implicated in apraxia of speech. The association of ideomotor apraxia and NVOA among patients without apraxia of speech could represent disruption of modules shared by nonverbal oral movements and limb movements.
| S-EPMC4032207 | biostudies-literature
Project description:In recent years a large and growing body of research has greatly advanced our understanding of primary progressive apraxia of speech. Handedness has emerged as one potential marker of selective vulnerability in degenerative diseases. This study evaluated the clinical and imaging findings in non-right handed compared to right handed participants in a prospective cohort diagnosed with primary progressive apraxia of speech. A total of 30 participants were included. Compared to the expected rate in the population, there was a higher prevalence of non-right handedness among those with primary progressive apraxia of speech (6/30, 20%). Small group numbers meant that these results did not reach statistical significance, although the effect sizes were moderate-to-large. There were no clinical differences between right handed and non-right handed participants. Bilateral hypometabolism was seen in primary progressive apraxia of speech compared to controls, with non-right handed participants showing more right hemispheric involvement. This is the first report of a higher rate of non-right handedness in participants with isolated apraxia of speech, which may point to an increased vulnerability for developing this disorder among non-right handed participants. This challenges prior hypotheses about a relative protective effect of non-right handedness for tau-related neurodegeneration. We discuss potential avenues for future research to investigate the relationship between handedness and motor disorders more generally.
| S-EPMC5986290 | biostudies-literature
Project description: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.
| S-EPMC3338923 | biostudies-literature
Project description:Primary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes.Sixteen primary progressive apraxia of speech subjects were age- and gender-matched to 16 progressive supranuclear palsy subjects and 20 controls. All subjects were prospectively recruited, underwent neurological and speech evaluations and 3.0-Tesla magnetic resonance imaging. Grey and white matter atrophy was assessed using voxel-based morphometry and atlas-based parcellation, and white matter tract degeneration was assessed using diffusion tensor imaging.All progressive supranuclear palsy subjects had typical oculomotor/gait impairments, but none had speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of the body of the corpus callosum. Whilst lateral grey matter loss was focal, involving superior premotor cortex, in primary progressive apraxia of speech, loss was less focal extending into prefrontal cortex in progressive supranuclear palsy. Caudate volume loss and tract degeneration of superior cerebellar peduncles were also observed in progressive supranuclear palsy. Interestingly, area of the midbrain was reduced in both syndromes compared to controls, although this was greater in progressive supranuclear palsy.Although neuroanatomical differences were identified between these distinctive clinical syndromes, substantial overlap was also observed, including midbrain atrophy, suggesting these two syndromes may have common pathophysiological underpinnings.
| S-EPMC3556348 | biostudies-literature
Project description:Apraxia of speech is a motor speech disorder thought to result from impaired planning or programming of articulatory movements. It can be the initial or only manifestation of a degenerative disease, termed primary progressive apraxia of speech (PPAOS). The aim of this study was to use task-free functional magnetic resonance imaging (fMRI) to assess large-scale brain network pathophysiology in PPAOS. Twenty-two PPAOS participants were identified from a prospective cohort of degenerative speech and language disorders patients. All participants had a comprehensive, standardized evaluation including an evaluation by a speech-language pathologist, examination by a behavioral neurologist and a multimodal imaging protocol which included a task-free fMRI sequence. PPAOS participants were age and sex matched to amyloid-negative, cognitively normal participants with a 1:2 ratio. We chose a set of hypothesis driven, predefined intrinsic connectivity networks (ICNs) from a large, out of sample independent component analysis and then used them to initialize a spatiotemporal dual regression to estimate participant level connectivity within these ICNs. Specifically, we evaluated connectivity within the speech and language, face and hand sensorimotor, left working memory, salience, superior parietal, supramarginal, insular and deep gray ICNs in a multivariate manner. The spatial maps for each ICN were then compared between PPAOS and control participants. We used clinical measures of apraxia of speech severity to assess for clinical-connectivity correlations for regions found to differ between PPAOS and control participants. Compared to controls, PPAOS participants had reduced connectivity of the right supplementary motor area and left posterior temporal gyrus to the rest of the speech and language ICN. The connectivity of the right supplementary motor area correlated negatively with an articulatory error score. PPAOS participants also had reduced connectivity of the left supplementary motor area to the face sensorimotor ICN, between the left lateral prefrontal cortex and the salience ICN and between the left temporal-occipital junction and the left working memory ICN. The latter connectivity correlated with the apraxia of speech severity rating scale, although the finding did not survive correction for multiple comparisons. Increased connectivity was noted in PPAOS participants between the dorsal posterior cingulate and the left working memory ICN. Our results support the importance of the supplementary motor area in the pathophysiology of PPAOS, which appears to be disconnected from speech and language regions. Supplementary motor area connectivity may serve as a biomarker of degenerative apraxia of speech severity.
| S-EPMC5964833 | biostudies-other
Project description:Primary progressive apraxia of speech (PPAOS) is a term used to describe a neurodegenerative condition in which apraxia of speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([18F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n = 4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n = 5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.
| S-EPMC7060829 | biostudies-literature
Project description:Primary progressive apraxia of speech (PPAOS) is a clinical syndrome in which apraxia of speech is the initial indication of neurodegenerative disease. Prior studies of PPAOS have identified hypometabolism, grey matter atrophy, and white matter tract degeneration in the frontal gyri, precentral cortex, and supplementary motor area (SMA). Recent clinical observations suggest two distinct subtypes of PPAOS may exist. Phonetic PPAOS is characterized predominantly by distorted sound substitutions. Prosodic PPAOS is characterized predominantly by slow, segmented speech. Demographic, clinical, and neuroimaging data (MRI, DTI, and FDG-PET) were analyzed to validate these subtypes and explore anatomic correlates. The Phonetic subtype demonstrated bilateral involvement of the SMA, precentral gyrus, and cerebellar crus. The Prosodic subtype demonstrated more focal involvement in the SMA and right superior cerebellar peduncle. The findings provide converging evidence that differences in the reliably determined predominant clinical characteristics of AOS are associated with distinct imaging patterns, independent of severity.
| S-EPMC6171111 | biostudies-literature
Project description:PurposeThis case series details the clinical progression of patients with primary progressive apraxia of speech (PPAOS) to illustrate, using several methods and supplemental material examples, the changes that occur in speech and language functioning in this patient population.MethodFour patients who presented with PPAOS were followed between 5 and 6 years. Two patients had predominant articulatory abnormalities (termed phonetic PPAOS), 1 had predominant prosodic abnormalities (prosodic PPAOS), and 1 had relatively equal articulatory and prosodic abnormalities (mixed PPAOS). Detailed speech (including acoustics), language, neurologic, and neuropsychological data were collected.ResultsAt initial exam, the patients ranged from 60 to 77 years old, with presenting disease duration of 1.5-10 years. Although all patients presented with an isolated apraxia of speech, all developed varying degrees of aphasia and dysarthria. Patients with phonetic PPAOS developed relatively more severe aphasia than the other 2 patients. All patients eventually had severe functional communication limitations and required alternative or augmentative means of communication, although at varying times postonset of their initial speech problem. Two patients developed dysphagia, 3 showed mild-moderate Parkinsonism, and 2 developed depression. For all patients, simple temporal acoustic measurements documented slowed speech rate over time.ConclusionsThis case series demonstrates that patients who initially present with PPAOS may develop aphasia and dysarthria, cognitive and behavioral changes, and other neurologic signs. Whether these changes can be predicted by the perceptual characteristics of the apraxia of speech is yet to be determined. The detailed longitudinal profiles provide valuable clinical insight into the progression of disease in people with PPAOS.Supplemental materialhttps://doi.org/10.23641/asha.7051616.
| S-EPMC6436456 | biostudies-literature
Project description:Apraxia of speech is a motor speech disorder characterized by combinations of slow speaking rate, abnormal prosody, distorted sound substitutions, and trial-and-error articulatory movements. Apraxia of speech is due to abnormal planning and/or programming of speech production. It is referred to as primary progressive apraxia of speech (PPAOS) when it is the only symptom of a neurodegenerative condition. Past reports suggest an association of PPAOS with primary 4-repeat (4R) tau (e.g., progressive supranuclear palsy, corticobasal degeneration), rather than amyloid, pathology. The goal of the current study was to investigate the distribution of tau tracer uptake using [18F]AV-1451 positron emission tomography (PET) imaging in patients with PPAOS. Fourteen PPAOS patients underwent [18F]AV-1451 PET (tau-PET) imaging, [C11] Pittsburgh Compound B (PiB) PET and structural MRI and were matched 3:1 by age and sex to 42 cognitively normal controls. Tau-PET uptake was assessed at the region-of-interest (ROI) level and at the voxel-level. The PPAOS group (n = 14) showed increased tau-PET uptake in the precentral gyrus, supplementary motor area and Broca's area compared to controls. To examine whether tau deposition in Broca's area was related to the presence of aphasia, we examined a subgroup of the PPAOS patients who had predominant apraxia of speech, with concomitant aphasia (PPAOSa; n = 7). The PPAOSa patients showed tau-PET uptake in the same regions as the whole group. However, the remaining seven patients who did not have aphasia showed uptake only in superior premotor and precentral cortices, with no uptake observed in Broca's area. This cross-sectional study demonstrates that elevated tau tracer uptake is observed using [18F]AV-1451 in PPAOS. Further, it appears that [18F]AV-1451 is sensitive to the regional distribution of tau deposition in different stages of PPAOS, given the relationship between tau signal in Broca's area and the presence of aphasia.
| S-EPMC5800944 | biostudies-literature