title: 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.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Neurology, Thomayer Teaching Hospital and Institute for Postgraduate Education in Medicine, Prague, Czech Republic. robert.rusina@ftn.cz
authors.forename: Robert
authors.initials: R
authors.lastname: Rusina
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.forename: Jindřich
authors.initials: J
authors.lastname: Fiala
authors.forename: Jakub
authors.initials: J
authors.lastname: Hort
authors.forename: Petr
authors.initials: P
authors.lastname: Ridzoň
authors.forename: Iva
authors.initials: I
authors.lastname: Holmerová
authors.forename: Thomas
authors.initials: T
authors.lastname: Ströbel
authors.forename: Radoslav
authors.initials: R
authors.lastname: Matěj
mesh_terms: D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000150:complications*; D006801:Humans; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000150:complications*; D010468:Perceptual Disorders / Q000150:complications*; D013494:Supranuclear Palsy, Progressive / Q000150:complications*; D057177:TDP-43 Proteinopathies / Q000503:physiopathology*; D014796:Visual Perception / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins