Clinicopathological characteristics of FTLD-TDP showing corticospinal tract degeneration but lacking lower motor neuron loss

Kobayashi, Zen; Tsuchiya, Kuniaki; Arai, Tetsuaki; Yokota, Osamu; Yoshida, Mari; Shimomura, Yoko; Kondo, Hiromi; Haga, Chie; Asaoka, Toshiyasu; Onaya, Mitsumoto; Ishizu, Hideki; Akiyama, Haruhiko; Mizusawa, Hidehiro

doi:10.1016/j.jns.2010.08.013

« Previous Next »Journal of the Neurological Sciences
Volume 298, Issue 1 , Pages 70-77, 15 November 2010

Clinicopathological characteristics of FTLD-TDP showing corticospinal tract degeneration but lacking lower motor neuron loss

Zen Kobayashi
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
- Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
- Corresponding author. Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo, 156-8585, Japan. Tel.: +81 3 3304 5701; fax: +81 3 3329 8035.
Kuniaki Tsuchiya
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Tetsuaki Arai
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
- Department of Psychiatry, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki 305-8577, Japan
Osamu Yokota
- Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
Mari Yoshida
- Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Aichi 480-1195, Japan
Yoko Shimomura
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Hiromi Kondo
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Chie Haga
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Toshiyasu Asaoka
- National Hospital Organization Shimofusa Psychiatric Medical Center, Chiba 266-0007, Japan
Mitsumoto Onaya
- National Hospital Organization Shimofusa Psychiatric Medical Center, Chiba 266-0007, Japan
Hideki Ishizu
- Department of Laboratory Medicine, Zikei Institute of Psychiatry, Okayama 702-8508, Japan
Haruhiko Akiyama
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Hidehiro Mizusawa
- Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan

Received 1 June 2010; received in revised form 30 July 2010; accepted 6 August 2010. published online 02 September 2010.

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 12years, 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.

Keywords: FTLD-TDP, Motor neuron disease, Amyotrophic lateral sclerosis, Primary lateral sclerosis, Corticospinal tract