Two studies from Sweden by the same team of investigators were of largely overlapping patient populations. They recruited cases from patient files of neurology clinics and departments (Flodin et al., 1988; Landtblom et al., 1993). The major differences between the studies were the years over which cases were recruited and the method of recruiting controls. For the earlier study (Flodin et al., 1988), controls were selected from previous participants in a cancer case-control study. The controls had been randomly selected from the population registries of the counties of interest, corresponding to the catchment areas of the hospitals with the MS cases. In the later study (Landtblom et al., 1993), the population registries of the catchment areas of the hospitals were used directly. The two studies used similar methods to ascertain exposure. Questionnaires were mailed to cases and controls. More than half the questions were related to occupational exposure. Some of the questions required more-detailed responses with respect to frequency, intensity, and duration of exposure. A minimum of 1 year of exposure was required, as was a 5-year latency period (that is, exposure that took place less than 5 years before disease onset was excluded). The 5-year latency period was selected to avoid inclusion of exposures that may have been a consequence of the disease itself, such as a diagnostic x-ray exposure. Exposure to ionizing radiation was also a risk factor considered in the case-control studies. A quantitative classification was developed to describe five levels of increasing exposure based strictly on occupational category (0=not exposed and 4=highest intensity of exposure).
The results of the 1988 Swedish study by Flodin and colleagues indicated a strong association between occupational exposure of men to solvents and MS (OR=3.1, 95% CI=1.4–6.8). There was an even stronger odds ratio for leisure-time exposure to solvents and MS (OR=16.2, 95% CI=2.8–92), but there were only four cases and two controls, and thus a very wide confidence interval. In another analysis, the combination of occupational exposure to solvents and welding resulted in a strong association (OR=13.2, 95% CI=3.4–51), but no association was observed for occupational exposure to solvents alone. No significant associations were observed in women. In the second Swedish study (Landtblom et al., 1993), solvent exposure (middle to high vs low to none) resulted in a moderate association in men and women combined (OR=2.8, 95% CI=1.3–5.5). In women only, there was no positive association. In men only, occupational solvent exposure was associated with MS, as was exposure specifically to kerosene. The authors speculated that solvents might contribute to MS by enhancing viral entry across the blood-brain barrier into the CNS.
Two case-control studies found no association between occupational solvent exposure and MS (Groning et al., 1993; Juntenen et al., 1989). The two studies conducted in Sweden found some positive associations with exposure to solvents, particularly in men. Those two studies were conducted with similar methods by the same group of investigators. The exposure classification was based on occupational category without the benefit of an occupational hygienist’s evaluation. No stated adjustment was performed for alcohol exposure or smoking. In addition, the timing of the exposure relative to the onset of MS is unknown, apart from its being more than 5 years before onset. Those studies raise suspicion, but they do not meet the committee’s criteria for “limited/suggestive” evidence, because of the potential for bias, including confounding.