From The MS Information Sourcebook, produced by the National MS Society.
A "cluster" of MS can be defined as the perception that a very high number of cases of MS have occurred over a specific time period and/or in a certain area. Such clusters of MS—or of other diseases where clusters are occasionally reported—are of interest because they may provide clues to environmental or genetic risk factors which might cause or trigger the disease. So far, cluster studies have not produced clear evidence for the existence of any causative or triggering factor or factors in MS.
Multiple sclerosis is known to occur in persons who have a genetically determined predisposition for the disease. However, a great deal of evidence suggests that most people who are genetically susceptible must still be exposed to some other factor or factors in their environment or in their life experience in order for MS to develop. Infectious agents are most often proposed as candidate triggering factors, but others have been examined, including environmental and industrial toxins, diet, trace metal exposures, and certain climatic elements such as sunlight. None has been shown to be causally linked to MS, and exactly what factor(s) may be involved remains an open question. There may in fact be more than one factor capable of triggering MS in susceptible individuals.
Clusters are Difficult to Investigate
First, it is difficult to determine what constitutes an "excess" of cases of MS. To do this, one needs to calculate the expected incidence of MS: that is, the number of new cases of MS that would be expected to occur in a given area over a given period of time, based on the total population at risk in the area. The expected incidence can then be compared with the reported incidence. Since MS is not infectious, and is therefore not a "reportable" disease according to the standards of the U.S. Centers for Disease Control, and because no nationwide MS registry exists, documented incidence rates (the "expected incidence") may not exist for an area where a cluster has been reported. The problem then becomes one of finding a suitable comparison population where the incidence of MS is known. This figure can help to determine the expected incidence of MS in the area where the cluster has been reported.
However, calculating an expected incidence rate is more complicated than this. MS rates are known to vary by latitude. Furthermore, MS occurs more often in women than men, and more often in individuals of Northern European ancestry than in others. Therefore, the expected incidence in an area must take into consideration not only the geographical location of that area, but also the age and sex distribution and ethnic makeup.
In addition, MS is more common in families where the disease already exists—an indication of the genetic susceptibility for the disease. Therefore, issues such as family relations within a reported cluster must also be taken into consideration.
A true cluster of MS means that there is a significantly higher incidence of definite MS in an area than expected. Surprising as it might seem, what may appear to be an extraordinary number of MS cases in one neighborhood or county may actually be no more than might be expected within that area.
Some of the other problems that make MS clusters difficult to investigate include:
Some Reported MS Clusters
The Faroe Islands
The most outstanding event that took place on the Faroes was the British occupation during World War II. Assuming an incubation period of a few years, this would tally with the onset of the first alleged epidemic in 1943. When researchers later grouped the cases of MS with clinical onset from 1943 to 1973 by puberty status at the time of the British occupation, they found three distinct peaks of MS incidence, corresponding to the three alleged epidemics. The first consisted of 18 cases, all of whom were past puberty at the time of the occupation. The second alleged epidemic consisted of 9 cases who were prepubertal during the occupation but who reached age 11 between 1941 and 1951, with onset of MS from 1948 to 1960. The third alleged epidemic comprised 5 cases who reached age 11 between 1949 and 1963, with onset of MS from 1965 to 1973.
Many of the occupation soldiers were from the Scottish Highlands, where the MS prevalence is quite high: 90 cases per 100,000, comparable to rates in the northern U.S. In Dr. Kurtzke's view, if MS is somehow triggered by a virus, the disease may have been brought to the Faroes by the occupying forces. Dr. Kurtzke is continuing his studies of MS in the Faroes, but in spite of years of intensive investigation, no factor has yet been identified that can definitively account for the alleged epidemics.
A 1991 analysis published in Neuroepidemiology by a team from the Ohio Department of Health found that 6 of the reported cases, or 24 percent, were not multiple sclerosis at all, but a different disease with similar symptoms—a case of misdiagnosis. The remaining 19 cases had definite or probable MS; however, of these, 2 cases were not residents of the area, and therefore were excluded from the prevalence calculation. The prevalence was still high, although it was within the range of what might be considered "normal."
The residents of this small town (population 1800) had been exposed to trace metals in water and soil from a zinc smelter plant that closed in the early 1980s. In conjunction with the Illinois Department of Public Health, the investigators confirmed the diagnoses of 9 people with MS, all of whom had developed symptoms between 1971-1990. Based on expected incidence rates, the investigators determined that the 9 cases far exceeded the number expected to occur over a two-decade time period in a town of this size. The authors concluded that exposure to zinc or other trace metals could have been a factor in the occurrence of this MS cluster, although they had no direct evidence that zinc or any other metal is, in fact, related to MS.
Rochester, New York
El Paso, Texas
The federal Agency for Toxic Substances and Disease Registry (ATSDR) of the Centers for Disease Control provided a grant to the Texas Department of Health to conduct a study among persons who had attended two elementary schools in the Kern Place/Mission Hills neighborhood and Smeltertown to determine the number of people who had been diagnosed with MS. Epidemiologist Judy P. Henry led the study, results of which were presented publicly on October 2, 2001 and may be published in the future.
Students who attended Mesita and E.B. Jones Elementary schools from 1948 through 1970 were eligible to be included in the study and were sent questionnaires asking for demographic and medical information. Dr. Randolph B. Schiffer reviewed the records of those who indicated they had MS to confirm the diagnosis.
The investigators identified and confirmed 14 cases of MS among former Mesita students. No cases were reported among former E.B. Jones students. The number of people with MS among former Mesita students is twice as high as expected, based on national estimates. This study was not designed to investigate the specific cause or causes of MS and the results cannot tell us why there is an excess of MS among the former Mesita students. Based on the findings, the investigators recommend further investigation of this cluster and possible factors that might be involved.
What If I Suspect an MS Cluster?
Murray TJ. Multiple Sclerosis: The History of a Disease. New York: Demos Medical Publishing, 2005.
Last updated February 2006