title: Clinicopathological characteristics of FTLD-TDP showing corticospinal tract degeneration but lacking lower motor neuron loss.
abstract: The presence of frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP) showing corticospinal tract (CST) degeneration but lacking lower motor neuron (LMN) loss has been reported, and the term primary lateral sclerosis (PLS) is used to distinguish motor neuron disease (MND) of these cases from amyotrophic lateral sclerosis (ALS). To date, however, details of clinicopathological findings of FTLD-MND-PLS type (FTLD-MND-P) have not been reported. We evaluated medical records and histopathological findings of ten cases of FTLD-MND-P, in comparison with those of six FTLD-MND-ALS type (FTLD-MND-A) cases. The mean age at onset and disease duration of FTLD-MND-P cases were 54 and 12 years, respectively. The first symptoms were frontotemporal dementia showing behavioral abnormality and/or personality change in five cases, semantic dementia in three cases, progressive non-fluent aphasia in one case, and auditory hallucination in one case. Upper motor neuron signs were clinically identified in six of the ten cases. There were no LMN signs throughout the clinical course in any case. Histopathologically, there was no obvious LMN loss or Bunina bodies in the hypoglossal nucleus or spinal cord in any case, whereas the CST was involved in all cases. The cerebral cortex of the six cases showed type 1 of TDP-43 histology defined by Cairns et al., whereas three cases showed type 3 histology, and one case showed type 2 histology. In all cases, TDP-43 positive neuronal cytoplasmic inclusions were absent or rare in the LMNs, while TDP-43 positive round structures were frequently identified in the neuropil of the spinal cord anterior horn in some cases. This study clarified that FTLD-MND-P cases have characteristic clinicopathological features distinct from those of FTLD-MND-A.
authors.affiliation: Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan. zen@bg7.so-net.ne.jp
authors.forename: Zen
authors.initials: Z
authors.lastname: Kobayashi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Arai
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokota
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kondo
authors.forename: Chie
authors.initials: C
authors.lastname: Haga
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Asaoka
authors.forename: Mitsumoto
authors.initials: M
authors.lastname: Onaya
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishizu
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002540:Cerebral Cortex / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D057174:Frontotemporal Lobar Degeneration / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology; D009046:Motor Neurons / Q000473:pathology*; D009410:Nerve Degeneration / Q000473:pathology*; D011712:Pyramidal Tracts / Q000473:pathology*; D057177:TDP-43 Proteinopathies / Q000473:pathology*; D016707:Tissue Fixation