Rapidly progressive atypical parkinsonism associated with frontotemporal lobar degeneration and motor neuron disease.
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.
Espay
Alberto J
AJ
Department of Neurology, Movement Disorders Center, The Neuroscience Institute, University of Cincinnati, Cincinnati, Ohio, USA.
Spina
Salvatore
S
Houghton
David J
DJ
Murrell
Jill R
JR
de Courten-Myers
Gabrielle M
GM
Ghetti
Bernardino
B
Litvan
Irene
I
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
D004268:DNA-Binding Proteins