0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Features of Patients With Nonfluent/Agrammatic Primary Progressive Aphasia With Underlying Progressive Supranuclear Palsy Pathology or Corticobasal Degeneration

Miguel A. Santos-Santos, MD1,2; Maria Luisa Mandelli, PhD1; Richard J. Binney, PhD3; Jennifer Ogar, MS1; Stephen M. Wilson, PhD4; Maya L. Henry, PhD5; H. Isabel Hubbard, PhD1; Minerva Meese, MS, CCC-SLP1; Suneth Attygalle, BS1; Lynne Rosenberg, BS1; Mikhail Pakvasa, BS1; John Q. Trojanowski, MD6; Lea T. Grinberg, MD, PhD1,7; Howie Rosen, MD1; Adam L. Boxer, MD, PhD1; Bruce L. Miller, MD1; William W. Seeley, MD1,7; Maria Luisa Gorno-Tempini, MD, PhD1
[+] Author Affiliations
1Department of Neurology, Memory Aging Center, University of California, San Francisco
2Department of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain
3Department of Communication Sciences and Disorders, Temple University, Philadelphia, Pennsylvania
4Department of Speech, Language, and Hearing Sciences, University of Arizona, Tucson
5Department of Communication Sciences and Disorders, University of Texas, Austin
6Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia
7Department of Pathology, University of California, San Francisco
JAMA Neurol. 2016;73(6):733-742. doi:10.1001/jamaneurol.2016.0412.
Text Size: A A A
Published online

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 data were 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 imaging may be useful for differentiating underlying PSP from CBD pathology during life.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Figures

Place holder to copy figure label and caption
Figure 1.
Cross-sectional Voxel-Based Morphometry at Presentation of Nonfluent/Agrammatic Primary Progressive Aphasia

T maps depicted at a P < .001 uncorrected threshold for better visualization of differences and similarities between groups. A 3-group analysis of variance was conducted for progressive supranuclear palsy (PSP; n = 5), corticobasal degeneration (CBD; n = 9), and control individuals (n = 80) using 4 covariates (age, scanner type, total intracranial volume, and sex). The color bar indicates t values (min = 0, max = 6). Images are in neurological view (left = left).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Longitudinal Voxel-Based Morphometry of Nonfluent/Agrammatic Primary Progressive Aphasia

T maps depicted at a P < .001 uncorrected threshold for better visualization of differences and similarities between groups. A 3-group analysis of variance was conducted for progressive supranuclear palsy (PSP; n = 5), corticobasal degeneration (CBD; n = 5), and control individuals (n = 42) using 4 covariates (age, scanner type, total intracranial volume, and sex). The color bar indicates t values (min = 0, max = 6). Images are in neurological view (left = left).

Graphic Jump Location

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

868 Views
0 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Make the Diagnosis: Does This Patient With Headaches Have a Migraine or Need Neuroimaging?

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Original Article: Does This Patient With Headache Have a Migraine or Need Neuroimaging?

brightcove.createExperiences();