Differential motor neuron involvement in progressive muscular atrophy: a comparative study with amyotrophic lateral sclerosis.
OBJECTIVE
Progressive muscular atrophy (PMA) is a clinical diagnosis characterised by progressive lower motor neuron (LMN) symptoms/signs with sporadic adult onset. It is unclear whether PMA is simply a clinical phenotype of amyotrophic lateral sclerosis (ALS) in which upper motor neuron (UMN) signs are undetectable. To elucidate the clinicopathological features of patients with clinically diagnosed PMA, we studied consecutive autopsied cases.


METHODS
Retrospective, observational.


METHODS
Autopsied patients.


METHODS
We compared clinicopathological profiles of clinically diagnosed PMA and ALS using 107 consecutive autopsied patients. For clinical analysis, 14 and 103 patients were included in clinical PMA and ALS groups, respectively. For neuropathological evaluation, 13 patients with clinical PMA and 29 patients with clinical ALS were included.


METHODS
Clinical features, UMN and LMN degeneration, axonal density in the corticospinal tract (CST) and immunohistochemical profiles.


RESULTS
Clinically, no significant difference between the prognosis of clinical PMA and ALS groups was shown. Neuropathologically, 84.6% of patients with clinical PMA displayed UMN and LMN degeneration. In the remaining 15.4% of patients with clinical PMA, neuropathological parameters that we defined as UMN degeneration were all negative or in the normal range. In contrast, all patients with clinical ALS displayed a combination of UMN and LMN system degeneration. CST axon densities were diverse in the clinical PMA group, ranging from low values to the normal range, but consistently lower in the clinical ALS group. Immunohistochemically, 85% of patients with clinical PMA displayed 43-kDa TAR DNA-binding protein (TDP-43) pathology, while 15% displayed fused-in-sarcoma (FUS)-positive basophilic inclusion bodies. All of the patients with clinical ALS displayed TDP-43 pathology.


CONCLUSIONS
PMA has three neuropathological background patterns. A combination of UMN and LMN degeneration with TDP-43 pathology, consistent with ALS, is the major pathological profile. The remaining patterns have LMN degeneration with TDP-43 pathology without UMN degeneration, or a combination of UMN and LMN degeneration with FUS-positive basophilic inclusion body disease.
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yuichi
Y
Riku
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Naoki
N
Atsuta
Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan.
Mari
M
Yoshida
Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan.
Shinsui
S
Tatsumi
Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan.
Yasushi
Y
Iwasaki
Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan.
Maya
M
Mimuro
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hirohisa
H
Watanabe
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mizuki
M
Ito
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Jo
J
Senda
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ryoichi
R
Nakamura
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Haruki
H
Koike
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Gen
G
Sobue
D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D001344:Autopsy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index