title: Concomitant alpha-synuclein pathology in an autopsy case of amyotrophic lateral sclerosis presenting with orthostatic hypotension and cardiac arrests.
abstract: A 74-year-old man gradually developed muscular weakness in the upper extremities, followed by dyspnea and dysarthria over a 6-month period. He was admitted to our facility and diagnosed as having amyotrophic lateral sclerosis (ALS) based on clinical and neurophysiological findings. Two months later, transtracheal positive pressure ventilation (TPPV) was started. During his clinical course, orthostatic hypotension occurred a few times. He also had two episodes of transient cardiac arrest, and he died 15 months after disease onset. At autopsy, the brain, weighing 850 g, showed diffuse cortical atrophy, preferentially involving the frontal lobes. Microscopic findings included severe loss of neurons in the motor cortex, the motor nuclei of the brainstem and the anterior horns of the spinal cord, and mild loss of axons and myelin in the corticospinal tract. Trans-activation response DNA protein 43 (TDP-43) immunoreactive cytoplasmic inclusions, the pathognomonic findings for ALS, were noted in the nucleus facialis, nucleus ambiguus, and in the anterior horn of the spinal cord. In addition, Lewy bodies and Lewy neurites were found in the brainstem and in the nucleus intermediolateralis of the thoracic cord. The concomitant alpha-synuclein pathology may have been partly related to possible autonomic dysfunction underlying the two episodes of cardiac arrest.
authors.affiliation: Division of Neurology, Ohmihachiman Community Medical Center, Ohmihachiman, Japan; Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Division of Neurology, Kyoto First Red Cross Hospital, Kyoto, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.forename: Koushun
authors.initials: K
authors.lastname: Matsuo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Youhei
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Koizumi
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shiga
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D001344:Autopsy; D001921:Brain / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017809:Fatal Outcome; D006323:Heart Arrest / Q000209:etiology*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000209:etiology*; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051844:alpha-Synuclein
keywords: Lewy body; amyotrophic lateral sclerosis (ALS); cardiac arrest; orthostatic hypotension; subclinical Parkinson's disease