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

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• 作者：Safa Al-Sarraj (1)
  Andrew King (1)
  Matt Cleveland (2)
  Pierre-Fran莽ois Pradat (3)
  Andrea Corse (4)
  Jeffrey D Rothstein (4)
  Peter Nigel Leigh (5)
  Bams Abila (2)
  Stewart Bates (2)
  Jens Wurthner (6)
  Vincent Meininger (3)
  
  1. Neuropathology ; Neuroscience Academic Building ; Kings College Hospital ; Denmark Hill ; London ; SE5 9RS ; UK
  2. Biopharm Translational Medicine ; GSK ; Stevenage ; UK
  3. D茅partement des Maladies du Syst猫me Nerveux ; APHP ; Reseau SLA IDF Groupe Hospitalier Piti茅-Salp锚tri猫re ; Sorbonne Universit茅s ; UPMC Univ Paris 06 ; INSERM ; CNRS ; Laboratoire d鈥橧magerie Biom茅dicale (LIB) ; Paris ; F-75005 ; France
  4. Department of Neurology ; Johns Hopkins School of Medicine ; 1800 Orleans Street ; Baltimore ; MD ; USA
  5. Division of Medicine (Neurology) ; Brighton and Sussex Medical School ; Trafford Centre for biomedical Research ; Falmer ; Brighton ; BN1 9RY ; UK
  6. Novartis Oncology Translational Medicine ; Basel ; Switzerland
  
• 关键词：Amyotrophic lateral Sclerosis ; Mitochondria ; Inflammation ; Pathology and Muscle
• 刊名：Acta Neuropathologica Communications
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：2
• 期：1
• 全文大小：2,538 KB
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• 刊物主题：Neurosciences;
• 出版者：BioMed Central
• ISSN：2051-5960

文摘

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.