title: Sporadic amyotrophic lateral sclerosis: Widespread multisystem degeneration with TDP-43 pathology in a patient after long-term survival on a respirator.
abstract: It has been reported that widespread multisystem degeneration can occur in patients with sporadic amyotrophic lateral sclerosis (SALS) who have survived for long periods with artificial respiratory support (ARS). We report a case of SALS of 8 years and 8 months duration in a 71-year-old woman, who received ARS for 7 years and 8 months. In this patient, the symptoms at the early stage were those of typical ALS, and a totally locked-in state with frontal lobe atrophy appeared a few years after the start of ARS. At autopsy, marked atrophy of the frontal lobe and brainstem tegmentum was evident. Microscopically, widespread multisystem degeneration with obvious neuronal loss was a feature. Bunina bodies and ubiquitinated inclusions were observed in the remaining lower motor neurons. Of interest was that Lewy body-like hyaline inclusions (LBHIs), which were later shown to be immunnoreactive (ir) for 43-kDa TAR DNA-binding protein (TDP-43) and ubiquitin, were also detected in neurons in various regions of the nervous system, including the lower and upper motor neuron nuclei. The distributions of neurons with TDP-43-ir and ubiquitin-ir cytoplasmic inclusions were also widespread in the nervous system, and in each region, the numbers of these neurons were apparently larger than those of neurons with LBHIs. Importantly, double-labeling immunofluorescence revealed that the widespread TDP-43-ir inclusions were often ubiqutinated. In conclusion, the entire pathological picture appeared to correspond well to the patient's long-standing, progressive disease, including the TDP-43 pathology with ubiquitination. These findings further strengthen the idea that TDP-43 abnormality is closely associated with the pathogenesis of SALS.
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nishihira
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Tan
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yonemochi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D012121:Respiration, Artificial
chemical_list: D004268:DNA-Binding Proteins