The Parkinson's-Reversing Breakthrough

Parkinson Disease Causes

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Some materials safety data sheets (MSDS) for welding consumables list parkinsonism as a potential hazard of welding, although the data upon which this claim is based is unclear. There are several clinical reports (80,83-85) of parkinsonism in welders, although many patients had atypical features, including cognitive abnormalities, disturbances of sleep, peripheral nerve complaints, and mild motor slowing. In a study of magnetic field exposed workers, Noonan et al. (70) found that welders were over-represented in PD deaths (70). Blood manganese (85) and aluminum (84) levels may be elevated in welders, but no study convincingly demonstrates an association between motor signs and these metals. However, a small study (84) suggests that welders with exposure to manganese may be slower on peg-board and finger-tapping scores compared to welders without these exposures. In one study, 15 career welders were compared to consecutively ascertained and age-matched PD controls. Welders with PD were clinically identical to the control groups except for a significantly younger age of onset (46 years) (86). [18F]FDOPA PET imaging in two welders with PD demonstrated reduced [18F]FDOPA uptake more prominent in the posterior putamen contralateral to the most affected side (86). The authors concluded that parkin-sonism in welders is distinguished clinically from idiopathic PD only by age of onset, suggesting that it may accelerate the onset of the disease. Levodopa responsiveness of parkinsonism in welders has been questioned by other investigators. Koller et al. (87) performed a double-blind, placebo-controlled study of levodopa in 13 welders with parkinsonism and found no difference in motor function. The reason for the differences between these studies is unclear. A recent study (88) of eight welders described syndromes of parkinsonism, myoclonus, and cognitive abnormalities associated with MRI abnormalities typical of manganese neurotoxicity, suggesting a broader potential phenotype among workers exposed to welding fumes. A recent survey (89) of three movement disorders clinics found only three welders among 2249 consecutive patients with PD; however, it is possible that welders were underrepresented in these relatively white collar communities.

Studies of large welder cohorts and epidemiologic studies provide contradictory evidence regarding a relationship between welding and parkinsonism. A pilot epidemiologic study (90) suggested that occupational welding may be more common in PD patients compared to patients with other neurological disorders; however, this study was not population based and the number of subjects studied was small. Several studies (68,91-94) have been cited as evidence against a relationship between parkinsonism and welding. One population-based study (91) of veteran twins found an odds ratio of 1.0 for welders, but this study was likely underpowered to detect a relationship, given that the investigators only studied eight welders. In a death certificate study (92) of neurodegenerative disease and PD, welding related occupations were not listed among the highest ranked occupations in PD-related deaths. However, death certificates may substantially underestimate the true prevalence of parkinsonism or PD, given the long clinical course and rarity of death due to PD-related morbidity. A case-control study (94) of PD and occupational exposures found no relationship with occupational exposure to heavy metals. However, only 19 PD subjects with metal exposure were studied, and welding as an occupation was not specifically identified. Other studies (51,93) have used broad occupational categories or reported exposure only to metals and did not specifically investigate welding. Several recent studies add to the controversy. A study (95) of 1423 Alabama welders referred for medical-legal evaluation found a substantially higher prevalence of parkinsonism in three standard occupational codes, using highly conservative assumptions. All patients were examined for parkinsonism with standardized videotaped assessments using the Unified Parkinson's Disease Rating Scale motor scale. Patients provided information regarding exposure to welding fumes and job titles. Job titles were matched with Department of Labor Standard Occupational Codes (SOCs). Diagnoses for parkinsonism were assigned using quantitative criteria. The prevalence of parkinsonism in Alabama welders was calculated by using the number of active welders in this screening with parkinsonism as the numerator and the age-adjusted number of welders in each SOC as the denominator. This prevalence calculation then was compared with general population data from Copiah County, Mississippi, U.S.A.. The estimated prevalence of parkinsonism among active male welders aged 40 to 69 statewide was 977 to 1336 cases/100,000 population. The prevalence of parkinsonism was higher among welders when compared to age-standardized data for the general population (prevalence ratio = 10.19, 95%CI 4.43-23.43). Lack of a contemporary control group and lack of blinding for welding trades as occupations were the important limitations.

A study (96) of occupations in a national death certificate database found an elevated mortality odds ratio of PD below age 65 in welders. However, there was no elevated mortality in the entire population of welders. A study (97) of Danish metal-manufacturing employees' hospitalization rates found no elevation in hospitaliza-tions for PD. PD is not typically a primary cause of hospitalization or death, although parkinsonian symptoms may contribute to morbidity from other diseases. Therefore, mortality rates and hospitalizations may not be sensitive indicators of parkin-sonism. Furthermore, the health and safety commitment in the Danish shipyards may be substantially greater than in the United States. A recently published study (98) in Sweden found no relationship between welding and PD in Sweden using nationwide, population-based registers. These methods are likely more sensitive than hospitalization data, but the findings do not necessarily preclude a greater risk of parkinsonism using more sensitive methods or a greater risk in workplaces with less rigorous environmental controls. These studies highlight the need for an epi-demiologic study using sensitive measures of parkinsonism and detailed dose reconstruction. The debate on the relationship between welding and parkinsonism will continue until this type of study is complete (99,100).

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