Case-control study in ALS using the National ALS Registry: lead and agricultural chemicals are potential risk factors.

Objective: To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods: P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained from medical records and structured interviews. P-ALS were followed prospectively for 2 years or until death, whichever came sooner. S-controls and age-, sex-, race/ethnicity-, and residential location-matched P-controls were recruited over 3 years. Occupational exposure to lead and agricultural chemicals (ACs) were assigned by an occupational hygienist, blinded to case status. OS biomarkers in urine were measured. Results: P-ALS (mean age 62.8 years; 63% males) resided across the United States. Demographic and socioeconomic variables did not differ among P-ALS, S-controls, and P-controls. P-ALS were more likely to report occupations with exposure to lead (adjusted OR (aOR)=2.3, 95% CI 1.1, 4.6) and ACs (aOR = 2.4, 95% CI 1.2, 4.6) compared to pooled controls. Among those with occupations with exposure to both lead and ACs, aOR was 7.2 (95% CI 2.0, 26.1). Urinary 8-oxo-dG was significantly elevated among P-ALS (11.07 ± 5.42 ng/mL) compared to S-controls, P-controls, or pooled controls (pooled 7.43 ± 5.42 ng/mL; p < 0.0001) but was not associated with occupational exposure to either lead or ACs. Conclusions: Findings reveal increased risk of ALS diagnosis among those with occupational exposure to lead and ACs and increased OS biomarkers among cases compared to controls. OS may be an important pathogenic mechanism in ALS.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Organochlorine pesticide exposure in essential tremor: a case-control study using biological and occupational exposure assessments.

Essential tremor (ET) is a common neurological disorder. Its etiology and pathogenesis are not well understood and several environmental factors (i.e., toxicants) have been studied. Organochlorine pesticides (OCPs) are potent tremor-producing chemicals. These pervasive environmental contaminants have been linked with other tremor disorders (e.g., Parkinson's disease) but they have not been assessed in ET cases. Our objective was to test the hypothesis that ET is associated with OCP exposure. Serum OCP concentrations and lifetime occupational histories were assessed in ET cases and control subjects. Six serum OCP concentrations (p,p'-DDE, p,p'-DDT, beta-hexachlorocyclo-hexane, oxychlordane, trans-nonachlor, and dieldrin) were assessed. Data from a lifetime occupational history were reviewed by a blinded industrial hygienist. The six serum OCP concentrations were similar in 136 ET cases and 144 control subjects. There was no association in ET cases between the six serum OCP concentrations and total tremor score. Three (2.2%) ET cases versus 9 (6.3%) controls had past occupational exposure to OCPs (OR=0.34, 95% CI=0.09-1.28, p=0.10). Although OCPs have been associated with other tremor disorders, we were not able to find an association between the six most tremorogenic OCPs and ET. Our data suggest that these tremor-producing chemicals are not of major etiological importance in our patients with ET.

Association between essential tremor and blood lead concentration.

Lead is a ubiquitous toxicant that causes tremor and cerebellar damage. Essential tremor (ET) is a highly prevalent neurologic disease associated with cerebellar involvement. Although environmental toxicants may play a role in ET etiology and their identification is a critical step in disease prevention, these toxicants have received little attention. Our objective was to test the hypothesis that ET is associated with lead exposure. Therefore, blood lead (BPb) concentrations were measured and a lifetime occupational history was assessed in ET patients and in controls. We frequency matched 100 ET patients and 143 controls on age, sex, and ethnicity. BPb concentrations were analyzed using graphite furnace atomic absorption spectrophotometry. A lifetime occupational history was reviewed by an industrial hygienist. BPb concentrations were higher in ET patients than in controls (mean +/- SD, 3.3 +/- 2.4 and 2.6 +/- 1.6 microg/dL, respectively; median, 2.7 and 2.3 microg/dL; p = 0.038). In a logistic regression model, BPb concentration was associated with diagnosis [control vs. ET patient, odds ratio (OR) per unit increase = 1.21; 95% confidence interval (CI), 1.05-1.39; p = 0.007]. BPb concentration was associated with diagnosis (OR per unit increase = 1.19; 95% CI, 1.03-1.37; p = 0.02) after adjusting for potential confounders. Prevalence of lifetime occupational lead exposure was similar in ET patients and controls. We report an association between BPb concentration and ET. Determining whether this association is due to increased exposure to lead or a difference in lead kinetics in ET patients requires further investigation.