Risk agents related to work and amyotrophic lateral sclerosis: An occupational medicine focus

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons. In recent years, in addition to several studies about genetic mechanisms leading to motor neurons damage, various epigenetic theories have been developed, involving the study of the patients' work and lifestyle. The work aims at focusing the role of occupational exposure related to ALS by literature data analysis. Articles, selected on the basis of keywords, year of publication and topics, are related to occupational exposure, suggesting an impact on ALS onset. The literature review shows that there are still a lot of biases in the studies design, which actually do not allow to draw unequivocal conclusions.

Atypical Levels of Heavy Metals, Creatinine, Haptoglobin, and Ferritin Found in Amyotrophic Lateral Sclerosis Outpatients vs. Healthy Controls: Possible Utility as a Diagnostic Biomarker

“…These samples were sent to the Pathology Laboratory at LabCorp Laboratory, Inc and analyzed using an electro chemiluminescent immunoassay or enzyme-linked immunosorbent assay (ELISA), ELECSYS 2010 (Roche Diagnostics, Indianapolis, IN) or Creatinine ICP-MS by Jaffe Method. The serum haptoglobin levels were measured in a hospital laboratory using a Beckman Coulter Unicel DXC by combining an antihaptoglobin antibody with the haptoglobin molecule, forming an insoluble complex [15]. This antigen-antibody complex was measured by optical absorbance at 340 nanometers using the turbidimetry principle.…”

“…A sensitization of motor neuron disease lymphocytes to neuronal membrane components released by denervated muscle and the cytotoxic activities of ALS plasma against erythrocytes has been demonstrated in the laboratory. These factors reacted with antibodies present in ALS plasma known to suppress terminal axonal sprouting and subsequent reinnervation of skeletal muscle [15,26]. If, in fact, haptoglobin is involved in the regulation of any part of the immunological response, one may interpret…”

Amyotrophic lateral sclerosis—A case report and mechanistic review of the association with toluene and other volatile organic compounds

“…Epidemiological studies evaluating the effects of occupational and environmental exposure to chemicals on morbidity and mortality in rates in ALS are difficult and often have limitations due to sample sizes and the use of retrospective exposure data . Unfortunately, most epidemiological studies of rare diseases such as ALS are retrospective observational studies that must rely on the diagnosis on a death certificate and occupational data to establish risk for exposure to a specific chemical that might be associated with working in a particular industry.…”

“…However, these studies are costly and take many years to complete. In addition, subjects who enter the study are often lost to follow‐up . Furthermore, many retrospective studies are constrained by having to use vague categories such as “pesticides,” metals or “solvents” with little regard for the specific mechanism of neurotoxic action of the pesticides or solvents used which can vary from one workplace to another even within the same industry.…”

“…But when the effect size is relatively small, as is often the case with an exposure and age at onset of a neurodegenerative disease in which most of the risk is attributable to age per se, retrospective studies can be biased toward underestimating risk. The result is that the epidemiological literature consists of widely variable results with one study finding an association with exposure to a particular chemical, class of chemicals, or occupation while another study does not . While prospective studies designed to monitor levels of exposure to specific compounds offer advantages over retrospective studies such studies are costly and take many years to conduct.…”