Poster: Selenium species and heavy metals in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: a hospital-based case-control study
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- Published on Wednesday, 10 October 2012 12:00
Background and aims: Amyotrophic lateral sclerosis (ALS) is one of the diseases which has been ascribed to overexposure to heavy metals and the metalloid selenium, but few data are still available on this issue, including the involvement of a specifies Selenium species, which have very different biological activities. Using an advanced analytical methodology, we designed a case-control study to test the association between selenium species and heavy metals with ALS risk, using as biomarker of exposure their concentrations in cerebrospinal fluid.
Methods: In a case-control study, we determined the Se compounds and the levels of Cd, Hg and Pb in cerebrospinal fluid samples of 38 ALS patients, recruited in the ALS Center of the Neurological Clinic of Modena University Hospital from May 1997 to April 2011, and of 38 reference neurological patients (16 men and 22 women; mean age 38 years) with signs or symptoms of suspected, but unconfirmed: liquoral hypertension or hypotension (3), primary headache (10), paresthesias with negative instrumental evidence (5), isolated idiopathic cranial nerve abnormalities (6) and other. The final diagnoses have been: migraine/cephalea (n=10), parhesthesias (7), cranic nerves abnormalities (6), mild mental confusion (3) and other disorders outside major neurological disease groups. The controls were matched 1:1 to the ALS cases for age (± 5 years) and for gender. Determinations of Se compounds and of the heavy metals was performed using high pressure liquid chromatography (HPLC) coupled with inductively coupled plasma - dynamic reaction cell - mass spectrometry (FI-ICP-DRC-MS) according to methodologies previously established and described by one of the coauthors (B.M.).
Results: We found higher levels of inorganic selenium species in the CSF of cases compared with controls. Conversely, the organic selenium forms were increased among controls, and this was particularly true for selenoprotein-P. Total selenium, determined in cases, was lower than that determined in
controls, since the levels of the inorganic forms merged to the 'uncertain' species, greatly exceed the higher levels detected in ALS patients for the
inorganic forms (Table 1). The correlation between inorganic and organic selenium and the single selenium compounds were generally similar in the ALS and control groups. Relative risk (RR) of ALS directly correlated with selenite content in both conditional and unconditional logistic models, while ALS risk was inversely associated with most organic selenium species. In multivariate analyses adjusting for the other categories of selenium compounds, the associations were generally stronger than in crude analyses (Table 2).
Conclusions: These results support the hypothesis that inorganic selenium may trigger the neurodegenerative process characterizing ALS. The lower levels of Se-containing enzymes in ALS patients may indicate a deficiency of antioxidant response against free-radicals damage. Instead, the results do not support an involvement of three heavy metals, Cd, Hg and Pb, in ALS etiopathogenesis. 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.
