TY - JOUR
T1 - The evolution of parkinsonism in primary progressive apraxia of speech
T2 - A 6-year longitudinal study
AU - Seckin, Zeynep Idil
AU - Duffy, Joseph R.
AU - Strand, Edythe A.
AU - Clark, Heather M.
AU - Utianski, Rene L.
AU - Machulda, Mary M.
AU - Botha, Hugo
AU - Ali, Farwa
AU - Thu Pham, Nha Trang
AU - Lowe, Val J.
AU - Whitwell, Jennifer L.
AU - Josephs, Keith A.
N1 - Funding Information:
This study was funded by National Institute of Health grants R01-DC12519, R01-DC010367, R01-DC14942 and R01-NS89757.
Funding Information:
Patient recruitment: The Neurodegenerative Research Group (NRG) at Mayo Clinic has been recruiting patients with progressive AOS into NIH-funded grants since July 2010. All patients undergo yearly longitudinal assessments including speech/language/neurological/neuropsychological evaluations, volumetric MRI and FDG-PET scans. To best capture the evolution of parkinsonism over a long time period we selected patients who had at least six yearly visits and who met published PPAOS criteria at onset [3]. Any patient with even mild (but unequivocal) evidence of aphasia or more than one PSP or CBS feature at onset was excluded. A total of eight patients met inclusion and exclusion criteria.Neurological evaluation: Neurologic examinations were performed by a Movement Disorders expert (KAJ). Parkinsonism was assessed with the MDS Sponsored revision of the Unified Parkinson's Disorder Rating Scale part-III (MDS-UPDRS-III) [15], limb apraxia with the WAB praxis subtest [16], and ocular motor impairment with the PSP Saccadic Impairment Scale (PSIS) [17] and PSP Rating Scale (PSPRS)-Ocular motor sub-scale [18]. Testing also included the Montreal Cognitive Assessment battery (MoCA) [19] for general cognition, Frontal Assessment Battery (FAB) [20] for executive function, and Neuropsychiatric Inventory Questionnaire (NPI-Q) [21] for neuropsychiatric features. Neurological diagnoses were determined at a consensus meeting involving three movement disorders and/or behavioral neurologists with expertise in degenerative parkinsonian disorders (KAJ, HB, FA). Cut-points to define abnormal were based on published data for: MoCA<26 [19]; FAB<16 [22] and NPI-Q>4 [23]. For the MDS-UPDRS-III, we used a cut-point of >7.95 and for the limb apraxia subset of the WAB, a cut-point of <60 suggested the presence of limb apraxia. Cut-points were calculated based on the 95th percentile of scores from a cohort of 21 motorically normal control subjects (median age = 67; range = [45, 85]; male/female = 10/11). That is, 95% of normal subjects scored ?7.95 on the MDS-UPDRS-III and 60 on the WAB praxis test. For ocular motor dysfunction, we used two different scales. For the PSIS, a score of 2 depicts slowing in vertical eye saccades and 3 or higher vertical supranuclear gaze palsy. For the ocular motor sub-score of the PSPRS, the total score was 12; a score of ?2 was considered as evidence of eye movement abnormalities.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Apraxia of speech
KW - Corticobasal syndrome
KW - PET
KW - PSP
KW - Parkinsonism
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U2 - 10.1016/j.parkreldis.2020.09.039
DO - 10.1016/j.parkreldis.2020.09.039
M3 - Article
C2 - 33045651
AN - SCOPUS:85092186182
SN - 1353-8020
VL - 81
SP - 34
EP - 40
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -