Familial amyotrophic lateral sclerosis with onset in bulbar sign, benign clinical course, and Bunina bodies : a clinical, genetic, and pathological study of a Japanese family

• Published in: Acta neuropathologica 2000-12, Vol.100 (6), p.603-607
• Main Authors: TSUCHIYA, K, SHINTANI, S, NAKABAYASHI, H, KIKUGAWA, K, NAKANO, R, HAGA, C, NAKANO, I, IKEDA, K, TSUJI, S
• Format: Article
• Language: English
• Subjects: Age; Aged; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - pathology; Amyotrophic Lateral Sclerosis - physiopathology; Biological and medical sciences; Brain - pathology; Brain - physiopathology; Bulbar Palsy, Progressive - genetics; Bulbar Palsy, Progressive - pathology; Bulbar Palsy, Progressive - physiopathology; Bunina bodies; Degeneration; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis; Dysarthria; Dysphagia; Female; Humans; Inclusion Bodies - genetics; Inclusion Bodies - pathology; Lewy bodies; Literature reviews; Male; Medical sciences; Middle Aged; Motor neurons; Motor Neurons - pathology; Mutation; Mutation, Missense - physiology; Nerve Degeneration - genetics; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Neurology; Pedigree; Point mutation; Spinal Cord - pathology; Spinal Cord - physiopathology; Spinocerebellar tract; Superoxide dismutase; Superoxide Dismutase - genetics; Ubiquitin
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s004010000237

We report a Japanese family with autosomal dominant adult-onset amyotrophic lateral sclerosis (FALS) with onset in the bulbar musculature, clinically benign course, absence of the Cu/Zn superoxide dismutase-1 (SOD 1) gene mutation, and many Bunina bodies, in addition to involvement of the upper and lower motor neurons. The proband was a Japanese woman who was 66 years old at the time of death. Family history disclosed five patients with FALS over three generations. She developed dysarthria at age 57, followed by dysphagia, muscle weakness of the upper extremities, and difficulty in respiration. She could walk without support until her death. The elder sister of the proband developed dysarthria at age 48 and died at age 58. A genetic study of the nephew of the proband showed the absence of a mutation in the SOD 1 gene. Neuropathological examination of the proband disclosed neuronal loss in the upper and lower motor neurons, and numerous Bunina bodies in the lower motor neurons without Lewy body-like inclusions or ubiquitin-immunoreactive neuronal inclusions. No degeneration of the Clarke's column, middle root zone of the posterior column, or posterior spinocerebellar tract was present. Review of the literature revealed that only patients with FALS with a long survival period of over 5 years had pathological findings consistent with FALS with posterior column involvement. This study contributes to the elucidation of the clinicopathological heterogeneity of FALS.