title: Rapidly progressive atypical parkinsonism associated with frontotemporal lobar degeneration and motor neuron disease.
abstract: OBJECTIVE
  To report the rare but distinct clinical and neuropathological phenotype of non-familial, rapidly progressive parkinsonism and dementia associated with frontotemporal lobar degeneration with motor neuron disease (FTLD-MND).
  
  
  METHODS
  Subjects included two 70-year-old women presenting with rapidly progressive severe postural instability, axial-predominant parkinsonism, oculomotor dysfunction and frontal-predominant dementia with language impairment and pseudobulbar palsy. One had diffuse weakness without signs of lower motor neuron disease. Post-mortem evaluations included immunohistochemistry with antiphospho-TAR DNA-binding protein 43 (TDP-43) and genetic analysis of the TARDBP and PGRN genes.
  
  
  RESULTS
  Subjects died within 14 months from symptom onset. TDP-43-positive neuronal intracytoplasmic inclusions were prominent in the primary motor cortex, granule cell layer of the hippocampus, and several cranial and spinal cord nuclei. TDP-43 globular glial inclusions (GGI) were identified in one case. There were no mutations in PGRN or TARDBP genes.
  
  
  CONCLUSIONS
  FTLD-MND due to TDP-43-proteinopathy should be considered in patients with rapidly progressive parkinsonism and dementia phenotype, especially when aphasia and/or weakness are also present.
authors.affiliation: Department of Neurology, Movement Disorders Center, The Neuroscience Institute, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Espay
authors.forename: Salvatore
authors.initials: S
authors.lastname: Spina
authors.forename: David J
authors.initials: DJ
authors.lastname: Houghton
authors.forename: Jill R
authors.initials: JR
authors.lastname: Murrell
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: de Courten-Myers
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Irene
authors.initials: I
authors.lastname: Litvan
mesh_terms: D000368:Aged; D001039:Aphasia, Broca / Q000209:etiology / Q000523:psychology; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000150:complications*; D006801:Humans; D007150:Immunohistochemistry; D016472:Motor Neuron Disease / Q000150:complications*; D009886:Ophthalmoplegia / Q000209:etiology; D010300:Parkinson Disease / Q000150:complications*; D020828:Pseudobulbar Palsy / Q000209:etiology; D057177:TDP-43 Proteinopathies / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins