1. 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
- Author
-
Matt Cleveland, Pierre-François Pradat, Jeffrey D. Rothstein, Stewart Bates, Vincent Meininger, Peter Leigh, Safa Al-Sarraj, Jens Würthner, Bams Abila, Andrea M. Corse, Andrew T. King, Neuropathology, Neuroscience Academic Building, Kings College London School of Medicine / Kings College Hospital, Biopharm Translational Medicine, GSK, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Johns Hopkins School of Medicine, Brighton and Sussex Medical School (BSMS), Novartis Oncology Translational Medicine, Laboratoire d'Imagerie Biomédicale (LIB), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Neurology ,Biopsy ,Inflammation ,Pathology and Forensic Medicine ,Cohort Studies ,Electron Transport Complex IV ,Cellular and Molecular Neuroscience ,Necrosis ,Atrophy ,Medicine ,Humans ,Pathology and Muscle ,Amyotrophic lateral sclerosis ,Muscle, Skeletal ,Denervation ,medicine.diagnostic_test ,business.industry ,Research ,Amyotrophic Lateral Sclerosis ,Skeletal muscle ,RNA-Binding Proteins ,Middle Aged ,medicine.disease ,Spinal cord ,Immunohistochemistry ,3. Good health ,Mitochondria ,DNA-Binding Proteins ,medicine.anatomical_structure ,RC0346 ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Female ,Neurology (clinical) ,medicine.symptom ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
BACKGROUND\ud \ud 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.\ud \ud AIM\ud \ud 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.\ud \ud MATERIAL AND METHODS\ud \ud 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.\ud \ud RESULTS\ud \ud 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.\ud \ud CONCLUSION\ud \ud 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.
- Published
- 2014
- Full Text
- View/download PDF