Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of motor neurons. Its etiology remains unknown, but several pathophysiological mechanisms are beginning to explain motor neuronal death, as well as oxidative stress. Iron accumulation has been observed in both sporadic and familial forms of ALS, including mouse models. Therefore, the dysregulation of iron metabolism could play a role in the pathological oxidative stress in ALS. Several studies have been undertaken to describe iron-related metabolic markers, in most cases focusing on metabolites in the bloodstream due to few available data in the central nervous system. Reports of accumulation of iron, high serum ferritin, and low serum transferrin levels in ALS patients have encouraged researchers to consider dysregulated iron metabolism as an integral part of ALS pathophysiology. However, it appears complicated to suggest a general mechanism due to the diversity of models and iron markers studied, including the lack of consensus among all of the studies. Regarding clinical study reports, most of them do not take into account confusion biases such as inflammation, renal dysfunction, and nutritional status. Furthermore, the iron regulatory pathways, particularly involving hepcidin, have not been thoroughly explored yet within the pathogenesis of iron overload in ALS. In this sense, it is also essential to explore the relation between iron overload and other ALS-related events, such as neuro-inflammation, protein aggregation, and iron-driven cell death, termed ferroptosis. In this review, we point out limits of the designs of certain studies that may prevent the understanding of the role of iron in ALS and discuss the relevance of the published data regarding the pathogenic impact of iron metabolism deregulation in this disease and the therapeutics targeting this pathway.

Highlights The sensitivity of evaluated SARS-CoV-2 immunoassays ranged from 95.6% to 97.8%. The specificity was 92.1% for Euroimmun IgG and ≥ 98.9% for Abbott IgG, Wantai Ab and DiaPro confirmation IgG assays. A lack of specificity was observed for low positive Euroimmun IgG results (ratio<5) and inconclusive RT-PCR results. A lack of sensitivity was observed for early serology (<14 days) or late RT-PCR testing (>30 days).

A 37-year-old man with no prior medical history except chronic alcohol and tobacco consumption was admitted for fever at 38.5°C and abdominal pain starting two days before. Physical examination confirmed tenderness of the left flank with no other abnormalities.…

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