Welding and Parkinson disease: is there a bond?

The cause of Parkinson disease (PD) remains unknown. Progress has been made on the genetic front with the identification of specific gene mutations (e.g., -synuclein) associated with familial Parkinson syndromes. Because of their clinical heterogeneity there remains debate as to whether these genetic syndromes are representative of what has been considered classical PD. The identification of mutations in the parkin and LRRK2 genes in both familial and sporadic PD1,2 suggest that genetic mutations may be more common than previously estimated. Despite these advances, at least 80% of PD cases do not have a clear genetic or familial basis. The knowledge that different genetic mutations can produce the PD phenotype suggests that perhaps there is no single clinical entity PD, but rather that PD is an amalgamation of many different conditions that simply have a greater or lesser degree of phenotypic overlap. However, most clinicians and scientists still endorse the classical concept of idiopathic PD. For the condition generally referred to as idiopathic PD and characterized by asymmetric onset of rest tremor, bradykinesia and rigidity, responsiveness to dopaminergic treatment, and the classic pathology of nigral degeneration with Lewy bodies, the cause remains unknown. Because genetic causes appear identifiable in only a minority of cases, there has been an extensive search for potential environmental causes. This search has been fueled by the identification of individuals who developed parkinsonism following exposure to MPTP through injection drug use and epidemiologic links between PD and environmental exposure to agricultural chemicals. Another environmental topic of recent interest has been the potential relationship between occupational welding fume exposure and PD. Welding fume is the cloud of smoke that is produced when welding metals. This fume, like cigarette smoke, is a combination of many different chemicals in a complex interaction. The fume contains manganese, iron, aluminum, chromium, nickel, and ozone. The health effects of welding have been the subject of clinical investigation for over 50 years. Recognition that manganese, one of the metals found in welding fume, is a neurotoxicant and can lead to a neurologic syndrome with parkinsonian features has led to speculation that manganese exposure through welding fumes might result in PD. Speculation around this question has been sufficient to prompt extensive litigation throughout the United States. Many experts researching and writing on this topic have been involved on one side or the other of this litigation, providing expert testimony, research data, or both. Hence this is an area where the reader (and the writer) need to be careful about recognition and disclosure of potential conflicts of interest (see ours). Two Neurology articles by Racette and others have described a potential relationship between welding and PD. In this issue of Neurology, two additional articles address this topic. The original Racette et al. article3 examined the clinical features of 15 out of approximately 1,000 patients with PD in a tertiary referral practice who reported welding as their occupation. When age matched with patients with PD of other occupations, the clinical features and demographics of the welders were the same. The age at onset of the welders was lower than a different control group that was not age matched, but this may have represented an age effect of sampling individuals still employed compared to those who were largely retired. The second Racette et al.4 article explored whether there is a higher than expected rate of parkinsonism in welders from Alabama. This study used an acceptable definition of parkinsonism, but one that was not sufficiently rigorous to define PD. A comparison was made to historical data derived from a PD epidemiologic survey done in Copiah County, Mississippi. The observed prevalence of parkinsonism in the studied welders was high, but it is not clear that the rate was higher than an appropriate control population. The current articles expand this inquiry. The re-