White matter lesions in FTLD: distinct phenotypes characterize GRN and C9ORF72 mutations

Abstract

Frontotemporal lobar degeneration (FTLD) has a high frequency of genetic forms; the 2 most common are GRN (progranulin) and C9ORF72 mutations. Recently, our group reported extensive white matter (WM) lesions in 4 patients with FTLD caused by GRN mutation, in the absence of noteworthy cardiovascular risk factors,(1) in line with other studies in GRN mutation carriers.(2,3) Here we compared the characteristics of frontal WM lesions in patients with behavioral variant of FTLD (bv-FTLD) caused by GRN and C9ORF72 mutations.

Figure. Visual score for the characterization of frontal WM lesions on FLAIR images

(A) Grade A: minor fluid-attenuated inversion recovery (FLAIR) hyperintensities, <4 mm thick, limited to the periventricular area, no extension into the deep and subcortical white matter (WM). Grade B: moderate FLAIR hyperintensities, <6 mm thick, affecting the periventricular and deep WM, no extension into the subcortical WM. Grade C: marked FLAIR hyperintensities, >6 mm thick, affecting periventricular, deep, and subcortical WM. (B) Frontal WM lesions were significantly different between groups on the left side (p < 0.0001, Kruskal-Wallis test) and on the right side (p = 0.007, Kruskal-Wallis test). Dunn post hoc tests showed statistically significant differences between the GRN group and controls and between the GRN group and the C9ORF72 group for the left and right side.