Clinical and MRI correlates of disease progression in a case of nonfluent/agrammatic variant of primary progressive aphasia due to progranulin (GRN) Cys157LysfsX97 mutation

J Neurol Sci. 2014 Jul 15;342(1-2):167-72. doi: 10.1016/j.jns.2014.03.058. Epub 2014 Apr 12.

Abstract

Little is known about the longitudinal changes of brain damage in patients with sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) and in progranulin (GRN) mutation carriers. This study reports the clinical and MRI longitudinal data of a patient with nfvPPA carrying GRN Cys157LysfsX97 mutation (GRN+). Voxel-based morphometry, tensor-based morphometry and diffusion tensor MRI were applied to evaluate gray matter (GM) and white matter (WM) changes over three years. The prominent clinical feature was motor speech impairment associated with only mild agrammatism. MRI demonstrated a progressive and severe GM atrophy of inferior fronto-insular-temporo-parietal regions with focal damage to frontotemporal and frontoparietal WM connections. This is the first report of longitudinal MRI data in a nfvPPA- GRN+ patient and this report offers new insights into the pathophysiology of the disease.

Keywords: Diffusion tensor MRI; Nonfluent/agrammatic variant of primary progressive aphasia; Progranulin; Tensor-based morphometry; Voxel-based morphometry; White matter damage.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrophy / pathology
  • Disease Progression*
  • Female
  • Gray Matter / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Magnetic Resonance Imaging
  • Middle Aged
  • Mutation
  • Neuroimaging
  • Primary Progressive Nonfluent Aphasia / diagnosis
  • Primary Progressive Nonfluent Aphasia / genetics*
  • Primary Progressive Nonfluent Aphasia / pathology*
  • Progranulins
  • White Matter / pathology

Substances

  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins