Journal
NEUROPATHOLOGY
Volume 29, Issue 6, Pages 689-696Publisher
WILEY
DOI: 10.1111/j.1440-1789.2008.00999.x
Keywords
artificial respiratory support; long-term survival; sporadic amyotrophic lateral sclerosis; TDP-43; ubiquitin
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology, Japan [20240037]
- Research Committee of CNS Degenerative Diseases
- Ministry of Health, Labour and Welfare, Japan
- Grants-in-Aid for Scientific Research [20240037] Funding Source: KAKEN
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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.
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