title: An autopsy case of sporadic amyotrophic lateral sclerosis associated with the I113T SOD1 mutation.
abstract: A 64-year-old man noticed weakness in his arms and dyspnea upon exertion. Four months later he was admitted to our hospital, where muscle atrophy and hyperactive deep tendon reflexes in the arms were observed upon examination. A needle electromyograph study revealed acute and chronic denervation in the extremities, and he was diagnosed as having amyotrophic lateral sclerosis (ALS). Seven months after onset of the disease, he died of respiratory failure. Neuropathologically, neuronal cell loss was observed in the motor cortex, hypoglossal nuclei, cervical and lumbar anterior horns and Clarke's nuclei. Some of the remaining neurons contained neurofilamentous conglomerate inclusions (CIs). A small number of Lewy body-like hyaline inclusions (LBHIs) were also observed. No the Bunina bodies, skein-like inclusions or basophilic inclusions were detectable. Tract degeneration was moderate in the dorsal and ventral spinocerebellar tracts, mild in the pyramidal tract, but not discerned in the posterior column. Immunohistochemical examinations revealed that the CIs were strongly positive for phosphorylated neurofilament and moderately positive for ubiquitin and Cu/Zn superoxide dismutase 1 (SOD1). Moreover, a number of phosphorylated tau protein-positive globose neurofibrillary tangles (NFTs) and threads were observed in the periaqueductal gray matter, oculomotor nuclei and trochlear nuclei. Although the family history was negative for neuromuscular diseases, the neuropathological findings indicated features of familial ALS with a SOD1 mutation. In fact, DNA analysis of frozen-brain tissue revealed the presence of the I113T SOD1 mutation. This case represents the first one of this mutation in a patient who showed CIs as well as LBHIs in the motor neurons at the same time, in addition to the NFTs in the mesencephalic tegmentum.
authors.affiliation: Department of Neurology, Kansai Medical University, Hirakata, Japan.
authors.forename: Seika
authors.initials: S
authors.lastname: Nakamura
authors.forename: Reika
authors.initials: R
authors.lastname: Wate
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Ito
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Oki
authors.forename: Ayako
authors.initials: A
authors.lastname: Tsuge
authors.forename: Masato
authors.initials: M
authors.lastname: Nagashima
authors.forename: Shinya
authors.initials: S
authors.lastname: Asayama
authors.forename: Kengo
authors.initials: K
authors.lastname: Fujita
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Maruyama
authors.forename: Hideshi
authors.initials: H
authors.lastname: Kawakami
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kusaka
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Lewy body-like hyaline inclusion; familial amyotrophic lateral sclerosis; neurofibrillary tangle; neurofilamentous conglomerate inclusion; sporadic amyotrophic lateral sclerosis