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. 2014 Jan 21;82(3):239-47.
doi: 10.1212/WNL.0000000000000031. Epub 2013 Dec 18.

In Vivo Signatures of Nonfluent/Agrammatic Primary Progressive Aphasia Caused by FTLD Pathology

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Free PMC article

In Vivo Signatures of Nonfluent/Agrammatic Primary Progressive Aphasia Caused by FTLD Pathology

Francesca Caso et al. Neurology. .
Free PMC article

Abstract

Objective: To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes.

Methods: We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD-transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at presentation in the whole group and in each pathologic subtype separately. We also considered longitudinal clinical data.

Results: At first evaluation, regardless of pathologic FTLD subtype, apraxia of speech (AOS) was the most common cognitive feature and atrophy involved the left posterior frontal lobe. Each pathologic subtype showed few distinctive features. At presentation, patients with nfvPPA-tau presented with mild to moderate AOS, mixed dysarthria with prominent hypokinetic features, clear agrammatism, and atrophy in the GM of the left posterior frontal regions and in left frontal WM. While speech and language deficits were prominent early, within 3 years of symptom onset, all patients with nfvPPA-tau developed significant extrapyramidal motor signs. At presentation, patients with nfvPPA-TDP had severe AOS, dysarthria with spastic features, mild agrammatism, and atrophy in left posterior frontal GM only. Selective mutism occurred early, when general neurologic examination only showed mild decrease in finger dexterity in the right hand.

Conclusions: Clinical features in sporadic nfvPPA caused by FTLD subtypes relate to neurodegeneration of GM and WM in frontal motor speech and language networks. We propose that early WM atrophy in nfvPPA is suggestive of FTLD-tau pathology while early selective GM loss might be indicative of FTLD-TDP.

Figures

Figure 1
Figure 1. Gray matter atrophy in nfvPPA pathologic subtypes vs controls
Voxel-based morphometric analysis on gray matter regions in nfvPPA pathologic subtypes relative to healthy controls. Statistical maps have been thresholded at p < 0.05 for FWE (top) and at p < 0.001 uncorrected (bottom). Statistical maps have shown in the coronal (coordinates [mm]: +0, +8) and axial (coordinates [mm]: +24, +48) sections of a T1-weighted MRI template image in DARTEL space. The color bar (hot) represents the t score. DARTEL = diffeomorphic anatomical registration through exponentiated lie; FTLD = frontotemporal lobar degeneration; FWE = familywise error; nfvPPA = nonfluent variant of primary progressive aphasia; TDP = transactive response DNA binding protein of 43 kD type A.
Figure 2
Figure 2. White matter atrophy in nfvPPA pathologic subtypes vs controls
Voxel-based morphometric analysis on white matter regions in nfvPPA pathologic subtypes relative to healthy controls. Statistical maps have been thresholded at p < 0.05 for FWE (top) and at p < 0.001 uncorrected (bottom). Statistical maps have shown in the coronal (coordinates [mm]: +0, +8) and sagittal (coordinates [mm]: −18, −4) sections of a T1-weighted MRI template image in DARTEL space. The color bar (winter) represents the t score. DARTEL = diffeomorphic anatomical registration through exponentiated lie; FTLD = frontotemporal lobar degeneration; FWE = familywise error; nfvPPA = nonfluent variant of primary progressive aphasia; TDP = transactive response DNA binding protein of 43 kD type A.

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