Selenium species and heavy metals in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: a hospital-based case-control study

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease which has been ascribed to overexposure to selenium and some heavy metals, on the basis of epidemiologic evidence and laboratory observations. However, no data are available on the specific involvement of single selenium species, all of which have distinctive biological activities, and limited evidence has also been provided for lead, mercury and cadmium in the human. Methods In a hospital-admitted case-control series, we determined the Se compounds and the levels of Cd, Hg and Pb in cerebrospinal fluid samples of thirty-six ALS patients and of thirty-six reference neurological patients. Determinations of Se compounds and of the heavy metals was performed using high pressure liquid chromatography coupled with inductively coupled plasma - dynamic reaction cell - mass spectrometry according to methodologies previously established and described by one of the coauthors (B.M.). Results We found an excess concentration of inorganic Se forms, particularly of the hexavalent and tetravalent ones, while organic Se compounds levels were considerably decreased in ALS cases. These differences were more pronounced in older patients and in females. On the converse, no substantial differences in Cd, Hg and Pb concentrations emerged. Conclusions These results suggest the occurrence of overexposure to inorganic Se species and decreased levels of Se-containing enzymes in ALS, while they offer little evidence of an involvement of three heavy metals, Cd, Hg and Pb, in the etiopathogenesis of this disease. However, caution must be used when inferring etiological clues from analytical results in patients affected by a severe disease such as ALS, and in hospital-referred controls. Further research on the involvement of Se in ALS etiology is clearly warranted.