Format

Send to

Choose Destination
Neurology. 2019 Mar 19;92(12):e1354-e1366. doi: 10.1212/WNL.0000000000007146. Epub 2019 Feb 15.

The underacknowledged PPA-ALS: A unique clinicopathologic subtype with strong heritability.

Author information

1
From the Brain and Mind Centre and Central Clinical School (R.H.T., B.G., C.D.-S., J.B.J.K., M.C.K., J.R.H., G.M.H.) and School of Medical Sciences (J.J.K.), Faculty of Medicine and Health, and Brain and Mind Centre and School of Psychology (O.P.), The University of Sydney; School of Medical Sciences (R.H.T., C.D.-S., G.M.H.), University of New South Wales & Neuroscience Research Australia; Department of Neurology (M.C.K.), Royal Prince Alfred Hospital; ARC Centre of Excellence in Cognition and its Disorders (J.R.H., O.P.); and Division of Neuroscience (B.G.), Garvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, New South Wales, Australia. rachel.tan1@sydney.edu.au.
2
From the Brain and Mind Centre and Central Clinical School (R.H.T., B.G., C.D.-S., J.B.J.K., M.C.K., J.R.H., G.M.H.) and School of Medical Sciences (J.J.K.), Faculty of Medicine and Health, and Brain and Mind Centre and School of Psychology (O.P.), The University of Sydney; School of Medical Sciences (R.H.T., C.D.-S., G.M.H.), University of New South Wales & Neuroscience Research Australia; Department of Neurology (M.C.K.), Royal Prince Alfred Hospital; ARC Centre of Excellence in Cognition and its Disorders (J.R.H., O.P.); and Division of Neuroscience (B.G.), Garvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, New South Wales, Australia.

Abstract

OBJECTIVE:

To assess the incidence, heritability, and neuropathology of primary progressive aphasia (PPA) with amyotrophic lateral sclerosis (ALS) in a large Australian cohort.

METHODS:

A total of 130 patients with a primary nonfluent variant of PPA (nfvPPA) or semantic variant of PPA (svPPA) were assessed for concomitant ALS and a strong family history of neurodegenerative diseases (Goldman score ≤3). Neuropathologic examination was carried out in 28% (n = 36) of these PPA and PPA-ALS cases that had come to autopsy.

RESULTS:

ALS was identified in 18% of patients with nfvPPA and 5% of patients with svPPA. PPA-ALS but not PPA was found to have a strong family history. At autopsy, frontotemporal lobar degeneration (FTLD)-TDP was identified in 100% of nfvPPA-ALS cases, 100% of svPPA-ALS cases, 24% of nfvPPA cases, and 78% of svPPA cases. Clinicopathologic assessments revealed a significant association between a strong family history and underlying FTLD-TDP pathology. Pathogenic mutations in known frontotemporal dementia (FTD)/ALS genes were identified in 100% of these familial PPA cases but only 50% of familial PPA-ALS cases, suggesting the involvement of novel genetic variants in this underacknowledged phenotype.

CONCLUSION:

The present study identified ALS in 12% of a large cohort of patients with nfvPPA and svPPA, which is comparable to the 10%-15% reported in FTD overall, indicating that a third of patients with FTD-ALS will have a predominant language profile. These findings highlight the importance of assessing for ALS in PPA, particularly since this is the only PPA phenotype in which a perfect clinicopathologic association has been reported in to date.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center