Features of patients with nonfluent/agrammatic primary progressive aphasia with underlying progressive supranuclear palsy pathology or corticobasal degeneration

Miguel A. Santos-Santos, Maria Luisa Mandelli, Richard J. Binney, Jennifer Ogar, Stephen M Wilson, Maya L. Henry, H. Isabel Hubbard, Minerva Meese, Suneth Attygalle, Lynne Rosenberg, Mikhail Pakvasa, John Q. Trojanowski, Lea T. Grinberg, Howie Rosen, Adam L. Boxer, Bruce L. Miller, William W. Seeley, Maria Luisa Gorno-Tempini

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy. OBJECTIVE To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up. DESIGN, SETTING, AND PARTICIPANTS A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included. MAIN OUTCOMES AND MEASURES Clinical, cognitive, and neuroimaging longitudinal datawere analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally. RESULTS Patient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms. CONCLUSIONS AND RELEVANCE In patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imagingmay be useful for differentiating underlying PSP from CBD pathology during life.

Original languageEnglish (US)
Pages (from-to)733-742
Number of pages10
JournalJAMA Neurology
Volume73
Issue number6
DOIs
StatePublished - Jun 1 2016

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Primary Progressive Nonfluent Aphasia
Progressive Supranuclear Palsy
Pathology
Atrophy
Neuroimaging
Dysarthria
Brain Stem
Autopsy
Language
Depression
Behavioral Symptoms
Functional Laterality
Deglutition
Short-Term Memory
Geriatrics
Healthy Volunteers
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Features of patients with nonfluent/agrammatic primary progressive aphasia with underlying progressive supranuclear palsy pathology or corticobasal degeneration. / Santos-Santos, Miguel A.; Mandelli, Maria Luisa; Binney, Richard J.; Ogar, Jennifer; Wilson, Stephen M; Henry, Maya L.; Hubbard, H. Isabel; Meese, Minerva; Attygalle, Suneth; Rosenberg, Lynne; Pakvasa, Mikhail; Trojanowski, John Q.; Grinberg, Lea T.; Rosen, Howie; Boxer, Adam L.; Miller, Bruce L.; Seeley, William W.; Gorno-Tempini, Maria Luisa.

In: JAMA Neurology, Vol. 73, No. 6, 01.06.2016, p. 733-742.

Research output: Contribution to journalArticle

Santos-Santos, MA, Mandelli, ML, Binney, RJ, Ogar, J, Wilson, SM, Henry, ML, Hubbard, HI, Meese, M, Attygalle, S, Rosenberg, L, Pakvasa, M, Trojanowski, JQ, Grinberg, LT, Rosen, H, Boxer, AL, Miller, BL, Seeley, WW & Gorno-Tempini, ML 2016, 'Features of patients with nonfluent/agrammatic primary progressive aphasia with underlying progressive supranuclear palsy pathology or corticobasal degeneration', JAMA Neurology, vol. 73, no. 6, pp. 733-742. https://doi.org/10.1001/jamaneurol.2016.0412
Santos-Santos, Miguel A. ; Mandelli, Maria Luisa ; Binney, Richard J. ; Ogar, Jennifer ; Wilson, Stephen M ; Henry, Maya L. ; Hubbard, H. Isabel ; Meese, Minerva ; Attygalle, Suneth ; Rosenberg, Lynne ; Pakvasa, Mikhail ; Trojanowski, John Q. ; Grinberg, Lea T. ; Rosen, Howie ; Boxer, Adam L. ; Miller, Bruce L. ; Seeley, William W. ; Gorno-Tempini, Maria Luisa. / Features of patients with nonfluent/agrammatic primary progressive aphasia with underlying progressive supranuclear palsy pathology or corticobasal degeneration. In: JAMA Neurology. 2016 ; Vol. 73, No. 6. pp. 733-742.
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abstract = "IMPORTANCE We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy. OBJECTIVE To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up. DESIGN, SETTING, AND PARTICIPANTS A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included. MAIN OUTCOMES AND MEASURES Clinical, cognitive, and neuroimaging longitudinal datawere analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally. RESULTS Patient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20{\%}]; 1 of 5 left-handed [20{\%}]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33{\%}]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98{\%} [80-100]; nfvPPA-CBD, 81{\%} [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms. CONCLUSIONS AND RELEVANCE In patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imagingmay be useful for differentiating underlying PSP from CBD pathology during life.",
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T1 - Features of patients with nonfluent/agrammatic primary progressive aphasia with underlying progressive supranuclear palsy pathology or corticobasal degeneration

AU - Santos-Santos, Miguel A.

AU - Mandelli, Maria Luisa

AU - Binney, Richard J.

AU - Ogar, Jennifer

AU - Wilson, Stephen M

AU - Henry, Maya L.

AU - Hubbard, H. Isabel

AU - Meese, Minerva

AU - Attygalle, Suneth

AU - Rosenberg, Lynne

AU - Pakvasa, Mikhail

AU - Trojanowski, John Q.

AU - Grinberg, Lea T.

AU - Rosen, Howie

AU - Boxer, Adam L.

AU - Miller, Bruce L.

AU - Seeley, William W.

AU - Gorno-Tempini, Maria Luisa

PY - 2016/6/1

Y1 - 2016/6/1

N2 - IMPORTANCE We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy. OBJECTIVE To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up. DESIGN, SETTING, AND PARTICIPANTS A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included. MAIN OUTCOMES AND MEASURES Clinical, cognitive, and neuroimaging longitudinal datawere analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally. RESULTS Patient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms. CONCLUSIONS AND RELEVANCE In patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imagingmay be useful for differentiating underlying PSP from CBD pathology during life.

AB - IMPORTANCE We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy. OBJECTIVE To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up. DESIGN, SETTING, AND PARTICIPANTS A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included. MAIN OUTCOMES AND MEASURES Clinical, cognitive, and neuroimaging longitudinal datawere analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally. RESULTS Patient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms. CONCLUSIONS AND RELEVANCE In patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imagingmay be useful for differentiating underlying PSP from CBD pathology during life.

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