Abstract
Exposure to neurotoxic chemicals such as pesticides, selenium, and heavy metals have been suggested to play a role in the etiology of amyotrophic lateral sclerosis (ALS). We assessed exposure to lead, cadmium, and mercury in 38 ALS patients (16 men and 22 females) and 38 hospital-admitted controls by using their cerebrospinal fluid (CSF) content as biomarker. We determined CSF heavy metal levels with inductively coupled plasma sector field mass spectrometry, according to a methodology specifically developed for this biological matrix. ALS patients had higher median values for Pb (155 vs. 132ng/L) but lower levels for Cd (36 vs. 72ng/L) and Hg (196 vs. 217ng/L). In the highest tertile of exposure, ALS odds ratio was 1.39 (95% CI 0.48-4.25) for Pb, 0.29 (0.08-1.04) for Cd and 3.03 (0.52-17.55) for Hg; however, no dose-response relation emerged. Results were substantially confirmed after conducting various sensitivity analyses, and after stratification for age and sex. Though interpretation of these results is limited by the statistical imprecision of the estimates, and by the possibility that CSF heavy metal content may not reflect long-term antecedent exposure, they do not lend support to a role of the heavy metals cadmium, lead and mercury in ALS etiology.
Highlights
The etiology of amyotrophic lateral sclerosis (ALS), an extremely severe neurodegenerative disease which selectively affects both the upper and the lower motor neurons, is still unknown, though in the so-called familial form a few gene mutations appear to play a major role [1,2].The etiology of the disease is still largely unknown, and environmental factors, alone or in the presence of particular genetic backgrounds, are believed to play a major role in it [2,3,4,5,6,7]
Median cerebrospinal fluid (CSF) concentrations in cases compared with controls were higher for lead, slightly lower for mercury and considerably lower for cadmium, with an interquartile range systematically wider for all the three metals
The odds of ALS were greater in the highest tertile of CSF Pb concentration than in the lowest tertile (OR = 1.4 in both multivariable-adjusted models), though confidence interval were rather wide
Summary
The etiology of the disease is still largely unknown, and environmental factors, alone or in the presence of particular genetic backgrounds, are believed to play a major role in it [2,3,4,5,6,7] These environmental factors include neurotoxic chemicals, such as pesticides, the metalloid selenium and a few heavy metals [4,8,9]. Among the latter, lead, cadmium, and mercury have been implicated in ALS etiology following toxicological and epidemiological observations [8,10,11]. We aimed at assessing a biomarker of heavy metal antecedent exposure, its cerebrospinal fluid (CSF) content, and its potential relation with ALS risk
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