Al-Sarraj, Safa, King, Andrew, Cleveland, Matt, Pradat, Pierre-François, Corse, Andrea, Rothstein, Jeffrey D, Leigh, Peter Nigel, Abila, Bams, Bates, Stewart, Wurthner, Jens and Meininger, Vincent (2014) Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minority of patients with amyotrophic lateral sclerosis; an observational myopathology study. Acta Neuropathologica Communications, 2 (1). p. 165. ISSN 2051-5960

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Abstract

BACKGROUND

Amyotrophic lateral sclerosis (ALS) is a primary progressive neurodegenerative disease characterised by neuronal loss of lower motor neurons (in the spinal cord and brainstem) and/or upper motor neurons (in the motor cortex) and subsequent denervation atrophy of skeletal muscle.

AIM

A comprehensive examination of muscle pathology from a cohort of clinically confirmed ALS patients, including an investigation of inflammation, complement activation, and deposition of abnormal proteins in order to compare them with findings from an age-matched, control group.

MATERIAL AND METHODS

31 muscle biopsies from clinically confirmed ALS patients and 20 normal controls underwent a comprehensive protocol of histochemical and immunohistochemical stains, including HLA-ABC, C5b-9, p62, and TDP-43.

RESULTS

Neurogenic changes were confirmed in 30/31 ALS cases. In one case, no neurogenic changes could be detected. Muscle fibre necrosis was seen in 5/31 cases and chronic mononuclear inflammatory cell infiltration in 5/31 (2 of them overlapped with those showing muscle necrosis). In four biopsies there was an increase in the proportion of cytochrome oxidase (COX) negative fibres (2-3%). p62 faintly stained cytoplasmic bodies in eight cases and none were immunoreactive to TDP-43.

CONCLUSION

This large series of muscle biopsies from patients with ALS demonstrates neurogenic atrophy is a nearly uniform finding and that mild mitochondrial abnormalities and low-grade inflammation can be seen and do not rule out the diagnosis of ALS. These findings could lend support to the notion that ALS is a complex and heterogeneous disorder.

Item Type:	Article
Schools and Departments:	Brighton and Sussex Medical School > Neuroscience
Subjects:	R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User:	Patricia Butler
Date Deposited:	26 Nov 2015 15:31
Last Modified:	02 Jul 2019 19:02
URI:	http://sro.sussex.ac.uk/id/eprint/54197

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