Louis, ED, EC Jurewicz, LK Applegate, P Factor-Litvak, M Parides, L Andrews, V Slavkovich, JH Graziano, S Carroll and A Todd. 2003. Association Between Essential Tremor and Blood Lead Concentration
Environmental Health Perspectives, on line 3 July 2003.

Nearly 10 million people in the US suffer from essential tremor (ET), a neurological disorder characterized by involuntary, rhythmic tremor of a body part, most typically the hands and arms. Experts attributed roughly half of the cases to familial genes. Little attention has been paid heretofore to possible environmental causes.

In this paper, Louis et al. report a significant association between blood lead levels and the risk of essential tremor, controlling for confounding variables. The association was strongest for ET victims without a family history of the disorder.

What did they do? Louis et al. found candidate patients with ET by reviewing health records at the Neurological Institute of New York (Columbia-Presbyterian Medical Center). Controls were then located out of the Manhattan phone book, matching them for age, gender and race to the controls. Patients and controls with signs of cognitive impairment or other neurological disorders like Parkinson's or multiple sclerosis were excluded from the study. The final sample size after screening was 100 patients and 143 controls.

Each participant (cases and controls) in the study underwent a videotaped tremor assessment to confirm the presence or absence of ET. These tapes were reviewed by a single expert in ET, who rated the patient's tremor during each of 12 tests on a scale of 0 to 3, which
resulted in a total tremor score (0 – 36 [maximum]).

The researchers analyzed blood lead levels in all subjects, and in a subset determined bone lead levels. Information was also obtained via questionnaire about family ET history and a range of potentially confounding variables, including age, race, history of smoking, factors reflecting socioeconomic status, potential for occupational exposure to lead, alcohol use, consumption of dietary supplements, etc.

What did they find? Blood lead levels were significantly but modestly elevated in patients with ET compared to controls. The median blood lead scores were 2.7 vs 2.3 µg/dL, respectively (p = 0.038). A series of other statistical analysis were all consistent with this basic finding. For example, they also found a weak but statistically significant correlation between total tremor score and blood lead level: the higher the lead level, the greater the score (p = 0.03).

The association was strengthened in an analysis looking only at ET patients without a family history of ET. In that comparison, median scores were 3.0 and 2.3 µg/dL (p = 0.003).

What does it mean? There are at least four possible interpretations of these findings.

• that lead increases the risk of ET;
• that ET and controls differ in their metabolism of lead, in a way that leads ET patients to have higher lead levels;
• the association is a statistical artifact because of some unidentified confounding variable;
• the result is a statistical fluke.

The last is unlikely because of the strength and consistency of the analyses. The other three are all plausible.

The elevation in risk of ET with such a small difference in blood lead levels suggests, however, that lead at that concentration alone could not be the sole determining factor. Otherwise, given prevailing lead blood lead levels within the US, a much larger percentage of the population would have ET than current data indicate (1-6%).

While offering no decisive conclusions, this paper provides an important service. Not only is it likely to stimulate more research into lead's role in the origins of ET, but it opens the window for research into other possible environmental causes of of the neurological disorder.