Corticobasal syndrome associated with the A9D Progranulin mutation

Salvatore Spina, Jill R. Murrell, Edward D. Huey, Eric M. Wassermann, Pietro Pietrini, Jordan Grafman, Bernardino Ghetti

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Corticobasal syndrome is characterized by cortical dysfunction and L-dopa-unresponsive Parkinsonism, with asymmetrical onset of clinical presentation and evidence of atrophy and/or hypometabolism at neuroimaging. Recently, the heterogeneous pathologic substrate of corticobasal syndrome has been further expanded to include cases with pathologic diagnosis of frontotemporal lobar degeneration with ubiquitin/TDP-43 (TAR DNA binding protein 43)-positive inclusions associated with progranulin (PGRN) mutations. We report a family in which several individuals have been affected with a dementia/movement disorder phenotype. The proband presented at age 45 with spontaneous left arm levitation, ideational apraxia, asymmetric parkinsonism, and dystonia. Subsequently, he developed limb-kinetic apraxia, left-side hemineglect, memory loss, and executive dysfunction. Magnetic resonance imaging and [F]fluorodeoxyglucose-positron emission tomography studies revealed severe cerebral cortical atrophy and hypometabolism, which were significantly more pronounced in the parietal lobes (right > left). Neuropathologic examination displayed the highest degree of degeneration and ubiquitin/TDP-43 pathology in the proband's parietal areas. Genetic analysis revealed the presence of the c.26C>A PGRN mutation in 1 allele. This mutation has been reported in association with hereditary-dysphasic-disinhibition-dementia, Alzheimer-like dementia, progressive supranuclear palsy, and primary progressive aphasia. The peculiar findings observed in this patient indicate that the parietal lobe may represent the most vulnerable anatomical area in some of the PGRN-associated frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusion cases.

Original languageEnglish (US)
Pages (from-to)892-900
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number10
DOIs
StatePublished - Oct 2007

Keywords

  • Alien limb
  • Apraxia
  • Frontotemporal lobar degeneration
  • Hemineglect
  • Parietal lobe
  • Progranulin
  • TDP-43

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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