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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
The problems associated with investigating clusters of any disease, and especially MS, are enormous.

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:

  • Uncertainty of the diagnosis of MS: What is believed to be MS and reported by a lay person as part of a cluster might include different diseases with similarities to MS. The difficulty of diagnosing MS accurately can make this problem worse.

  • Lag time between clinical onset and diagnosis: Since the first symptoms of MS often occur years before the disease is diagnosed, a person diagnosed with MS in an area where a cluster has been reported may actually have had clinical onset of MS somewhere else.

  • Coincidence: As hard as it is to believe, it is possible for clusters to happen by chance, with no common factor(s) causing the cases of MS that make up the cluster.

Some Reported MS Clusters

The Faroe Islands
One of the earliest and most famous group of clusters known to MS investigators are a series of alleged epidemics that occurred on the Faroe Islands, a Danish possession lying in the north Atlantic between Norway and Iceland. Although the inhabitants are Nordic and considered a high-risk group for the disease, there were no known reports of MS prior to 1943 among native-born residents. In the early 1960s a Washington, D.C. neurologist, Dr. John Kurtzke, became intrigued with a report by a Danish investigator, K. Hyllested, about 25 cases of MS in the Faroes that had occurred starting in 1943. It appeared that the disease had been brought into the Faroes since it hadn't been reported there before.

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.

Galion, Ohio
Galion, Ohio, with a population of 12,391, was reported to have 25 cases of MS in 1986, a prevalence about double what might be expected. Nothing in the history of Galion pointed to any common agent, except that in 1960 a patch of land on part of an old cemetery was dug up so that a new high school gymnasium could be built. The loose earth was offered to anyone who would take it away. Many did.

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."

DePue, Ilinois
MS clusters may sometimes crop up in occupational settings. Dr. Randolph B. Schiffer (Texas Tech University Health Sciences Center , Lubbock) and colleagues undertook an investigation of an industry-based MS cluster in DePue , Illinois in the late 1990s, results of which were published in the September/October 2001 issue of Archives of Environmental Health.

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
Zinc might be of particular interest because it was also identified as a possible exposure factor in an earlier report by Drs. E.C. Stein, Schiffer and colleagues, published in the October 1987 issue of Neurology , describing an MS cluster among employees at a manufacturing plant in Rochester, New York . When the investigators checked workers' records, they found that 11 had developed MS during a 10-year period, 1970-79, when 2 to 4 cases would have been expected. Even though the investigators concluded that there was a significant excess of cases of MS, they could find no differences in exposure to zinc between the workers who had developed MS and those who had not. However, genetic susceptibility to MS was not taken into account in the investigation.

El Paso, Texas
In December 1994, a former El Paso, Texas resident with MS contacted the Texas Department of Health to report an apparent cluster of MS cases among people who spent their childhoods in the Kern Place/Mission Hills and Smeltertown areas of El Paso . Early in the investigation, concerns were raised about the possible impact of a local metal smelter, which was shown to have contaminated the air and soil with high levels of metals such as lead, arsenic, zinc, and cadmium.

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.

Other Clusters
Over the years, other MS clusters have been reported, but epidemiologists have been unable to pinpoint any definite causes. Research into reported MS clusters continues. In 2002, the federal Agency for Toxic Substances and Disease Registries (ATSDR) awarded research grants to five investigators to evaluate possible environmental risk factors for MS and amyotrophic lateral sclerosis (ALS) in several communities in the United States that are located near hazardous waste sites. These studies are ongoing in Illinois, Texas, Massachusetts, Eastern Washington, and Missouri. While these efforts of ATSDR to understand the potential health risks of hazardous waste exposure will provide important information, there is no information to date to suggest a definite link between hazardous waste and MS.

What If I Suspect an MS Cluster?
The major resource for individuals with concerns or questions about an MS cluster in their community is the local (town, city or state) public health department. Public health officials are primed to hear about, and to investigate, suspected clusters. They may also have the resources—local staffing and funding— to pursue analyses of situations that they consider to be of concern, or may refer such cases to the federal Centers for Disease Control's Agency for Toxic Substances and Disease Registry. Consumers may contact this agency by calling toll-free 1-888-422-8737, e-mail ATSDRIC@cdc.gov, or by visiting their Web site at www.atsdr.cdc.gov/

See also...



Society Web Resources


Murray TJ. Multiple Sclerosis: The History of a Disease. New York: Demos Medical Publishing, 2005.




Last updated February 2006