Recent evidence shows that in amyotrophic lateral sclerosis (ALS), there occurs a notable deposition of abnormal ubiquitinated inclusions immunoreactive to TDP-43. In order to provide an early diagnosis and to conduct clinical trials for early treatment for ALS, it is crucial to fully understand muscle pathology in this condition. The study, entitled, “Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minorityof patients with amyotrophic lateral sclerosis; an observational myopathology study”, was recently published in the journal Acta Neuropathologica Communications.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by neuronal loss in the lower motor neurons and/or upper motor neurons, causing denervation and atrophy of skeletal muscle.
Safa Al-Sarraj from the Kings College Hospital, Denmark Hill, London, and colleagues, analyzed muscle pathology, including inflammation, complement activation, and deposition of abnormal proteins in 31 muscle samples from biopsies of patients with ALS. The researchers then compared these samples with those obtained from 20 healthy volunteers, within the same age range. For ALS patients, the weaker of the two deltoid muscles was chosen. A muscle specimen of an approximate size of 1.0 cm × 0.5 cm× 0.5 cm was collected per subject. Then, both groups were assessed for histochemical and immunohistochemical stains, including HLAABC, C5b-9, p62, and TDP-43. After analysis, of the 31 ALS cases, 30 were found to have neurogenic changes.
Muscle fiber necrosis was observed in 5 ALS cases. The other 5 cases were found to have chronic mononuclear inflammatory cell infiltration. In 4 cases, the researchers found an increase of 2-3% in the amount of cytochrome oxidase negative fibres. Furthermore, in 8 cases the researchers found p62 faintly stained cytoplasmic bodies, with none of the bodies being immunoreactive to TDP-43.
In this study, Safa Al-Sarraj and colleagues were able to clearly demonstrate chronic neurogenic atrophy in muscle biopsies of ALS patients. Moreover, the researchers found low grade endomysial and perimysial chronic inflammation and mitochondrial alterations in a small portion of muscle biopsies from patients with sporadic ALS, beyond that seen in age-matched control biopsies.
In the article the authors concluded that “these findings could reflect contributing pathogenic mechanisms whereby additional oxidative stress by inflammation or other factors could unmask subclinical mitochondrial dysfunction in the muscle of some ALS patients”. Results from this study, strongly support the view that ALS is a multifactorial disorder needing further research.