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Open Access Case report

FTLD-TDP with motor neuron disease, visuospatial impairment and a progressive supranuclear palsy-like syndrome: broadening the clinical phenotype of TDP-43 proteinopathies. A report of three cases

Robert Rusina1*, Gabor G Kovacs2, Jindřich Fiala1, Jakub Hort34, Petr Ridzoň1, Iva Holmerová5, Thomas Ströbel2 and Radoslav Matěj67

Author Affiliations

1 Department of Neurology, Thomayer Teaching Hospital and Institute for Postgraduate Education in Medicine, Prague, Czech Republic

2 Institute of Neurology, Medical University of Vienna, Vienna, Austria

3 Department of Neurology, Charles University, 2nd Medical Faculty and Motol Teaching Hospital, Prague, Czech Republic

4 International Clinical Research Center, Brno, Czech Republic

5 Centre of Gerontology and Faculty of Humanity Studies, Charles University in Prague, Prague, Czech Republic

6 Department of Pathology and Molecular Medicine, Thomayer Teaching Hospital, Prague, Czech Republic

7 Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, Czech Republic

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BMC Neurology 2011, 11:50  doi:10.1186/1471-2377-11-50

Published: 10 May 2011

Abstract

Background

Frontotemporal lobar degeneration with ubiquitin and TDP-43 positive neuronal inclusions represents a novel entity (FTLD-TDP) that may be associated with motor neuron disease (FTLD-MND); involvement of extrapyramidal and other systems has also been reported.

Case presentation

We present three cases with similar clinical symptoms, including Parkinsonism, supranuclear gaze palsy, visuospatial impairment and a behavioral variant of frontotemporal dementia, associated with either clinically possible or definite MND. Neuropathological examination revealed hallmarks of FTLD-TDP with major involvement of subcortical and, in particular, mesencephalic structures. These cases differed in onset and progression of clinical manifestations as well as distribution of histopathological changes in the brain and spinal cord. Two cases were sporadic, whereas the third case had a pathological variation in the progranulin gene 102 delC.

Conclusions

Association of a "progressive supranuclear palsy-like" syndrome with marked visuospatial impairment, motor neuron disease and early behavioral disturbances may represent a clinically distinct phenotype of FTLD-TDP. Our observations further support the concept that TDP-43 proteinopathies represent a spectrum of disorders, where preferential localization of pathogenetic inclusions and neuronal cell loss defines clinical phenotypes ranging from frontotemporal dementia with or without motor neuron disease, to corticobasal syndrome and to a progressive supranuclear palsy-like syndrome.