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Rapidly progressive atypical parkinsonism associated with frontotemporal lobar degeneration and motor neuron disease
  1. Alberto J Espay1,
  2. Salvatore Spina2,3,
  3. David J Houghton4,
  4. Jill R Murrell2,
  5. Gabrielle M de Courten-Myers5,
  6. Bernardino Ghetti2,
  7. Irene Litvan4
  1. 1Department of Neurology, Movement Disorders Center, The Neuroscience Institute, University of Cincinnati, Cincinnati, Ohio, USA
  2. 2Indiana Alzheimer Disease Center, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
  3. 3Department of Neurological, Neurosurgical and Behavioural Sciences, University of Siena, Siena, Italy
  4. 4Department of Neurology, Division of Movement Disorders Center, University of Louisville, Louisville, Kentucky, USA
  5. 5Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA
  1. Correspondence to Dr Salvatore Spina, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Drive MS A134, Indianapolis, IN 46202, USA; sspina{at}


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.

  • Frontotemporal lobar degeneration
  • atypical parkinsonism
  • dementia
  • TDP-43
  • globular glial inclusions
  • oligodendrogliopathy

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  • Funding This work was sponsored in part by research grants NIH PHS AG010133 (BG) and R01 PAS-03-092 NIA (IL).

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.