Military personnel serving during the first Gulf War have one of the highest incidence rates for multiple sclerosis (MS) ever reported, leading to speculation that environmental exposures in the war zone triggered the disease. Research trying to determine causes, however, came up with a surprising result: The servicemembers at the greatest risk were those who were never deployed.
By Annette M. Boyle
WASHINGTON — The first Gulf War cohort has one of the highest incidence rates for multiple sclerosis (MS) ever reported. Were the veterans at greatest risk those who:
- Tended oil fires?
- Were exposed to chemical weapons?
- Contracted endemic infectious diseases?
- None of the above?
In a surprising twist to this mystery, recent research indicates that the servicemembers most likely to develop multiple sclerosis had none of the exposures hypothesized as risk factors. Instead, the highest risk occurred in those who were not deployed in the 1990-1991 Gulf War.
“We found that there was no increase in risk across the board for any group in Gulf War I,” said Mitchell Wallin, MD, MPH, clinical associate director for the VA’s MS Center of Excellence-East and associate professor of neurology at Georgetown University School of Medicine in Washington. “That doesn’t mean deployment anywhere won’t increase risk, but deployment in the first Gulf War was not a risk factor. We didn’t look at the Operation Enduring Freedom, Operation Iraqi Freedom or Bosnia cohorts.”
Previous research by Wallin and his VA colleagues found an MS incidence rate of 7.3 per 100,000 men and 24.7 per 100,000 women in the Gulf War cohort. “The age-specific rates for the cohort are among the highest seen in comparable populations,” Wallin told U.S. Medicine, but he added that very few incidence studies exist for MS, and none includes as diverse a population base as the military study. 1
Based on the incidence rates, looking for risk factors in deployment seemed like a logical next step for research. “The rates for MS are very high in the military, and we wanted to know what was going on. It was evident that those deployed in theater had exposures including viral infections, vaccines, air pollutants and central nervous system toxins. Could those exposures have triggered MS?”
The researchers looked at all active-duty military and activated Reserve and National Guard who served between Aug. 1, 1990, and Dec. 31, 1991. “This wasn’t a sample. There were over 1,800 cases of MS in the cohort, out of 700,000 deployed servicemembers and 1.8 million nondeployed. If there was a signal there, anything that increased risk, we would have found it,” Wallin said.
The researchers drew on medical records from the DoD and VA to find service-related cases of MS between 1990 and 2007. Among the 696,118 deployed personnel, 387 developed MS. Of the 1,786,215 nondeployed servicemembers, 1,457 incident cases of MS were found.
Deployment was not significant across almost all groups and appeared to be protective among whites, males, members of the Air Force, Army and Navy and for all groups under 44 years of age. Overall, deployed personnel had about two-thirds the risk of developing MS compared to nondeployed individuals. For whites, the relative risk was 0.62 and for blacks, 0.83.
Notably, “Marines had half the rates of other services, yet they had the longest deployments and were most likely to be deployed,” Wallin added.
A subset analysis looked at the soldiers exposed to nerve agents, including sarin and cyclosarin released when U.S. forces detonated the Khamisiyah Iraqi weapons cache in March 1991. Of the estimated 100,487 Army veterans exposed to the chemical weapons, 65 developed MS. For this group, the relative risk was a non-significant 1.10.
In a poster presentation at the 2013 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), the researchers candidly noted, “we were somewhat surprised by the direction of the RR estimates. With the potential risk factors for MS found in the GWI theater of operations, why wouldn’t there be a higher or at least neutral risk of MS among those deployed?”2
They hypothesized that the “healthy soldier effect,” often used to explain why military forces have lower rates for many diseases than their civilian counterparts, may occur even within the military. “This effect hypothesizes that deployed personnel are likely to be healthier than the general military population due to selection and screening for physical characteristics by the armed services. This selection bias toward a healthier deployed force is supported by data on hospitalization rates and separation from military service due to medical disqualification in active duty forces prior to and immediately after GWI.”
With deployment ruled out as a risk factor, the researchers have turned their focus to identifying other potential factors driving the high rate of MS among veterans. “Maybe there are features in military service we don’t know about. There could be other risks,” Wallin said.
Vitamin D levels may play a role, as some research has found that high levels are protective in whites and low levels may increase risk, Wallin noted. Epstein-Barr virus also has been suggested as a risk factor.
“Virtually all adults have the virus, but potentially those exposed later in life — those in Western nations with high hygiene — may have increased risk,” he postulated. “We know geography matters, that MS is more common in northern-tier states than in southern states, although there has been some diffusion of risk over time.”
The remarkably high rate in females puzzles Wallin and his VA colleagues perhaps as much as the overall high rates among U.S. veterans. “What’s contributing to the development of MS in females at more than three times the rate of males, across all service branches? That result is consistent with multiple studies in multiple continents that show women are increasingly developing MS at higher rates than men over the last 100 years,” he asked.
The U.S. military cohorts analyzed over the past 60 years show the trend quite clearly. In the World War II/Korean Conflict cohort, the relative risk of MS among white women was 1.8; in the Vietnam and later cohort rising to 3.0; and in the Gulf War cohort, it is 3.5.
“The relative risk of developing multiple sclerosis has always been higher for females than for males, but exhibits striking temporal changes, as it doubles for white females, and even triples for black females,” noted the late Christian Confavreaux, MD, formerly of the Department of Neurology at the Hôpital Neurologique Pierre Wertheimer in Lyon, France, in a commentary on the MS research. 3
The overall incidence rate may have risen because of increased surveillance, the use of magnetic resonance imaging to definitively diagnose MS and greater awareness of the disease as therapeutic agents have emerged, Wallin said.
But, “the increase in women can’t be explained by technology alone,” he said. With growing numbers of women veterans, the VA has a keen interest in finding out exactly what does explain the much higher rates of MS in women.
1 Wallin MT, Culpepper WJ, Coffman P, Pulaski S, Maloni H, Mahan CM, Haselkorn JK, Kurtzke JF; Veterans Affairs Multiple Sclerosis Centres of Excellence Epidemiology Group. The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex and service. Brain. 2012 Jun;135(Pt 6):1778-85.
2 Wallin MT, Mahan C, Maloni H, Culpepper WH, Coffman P, Kurtzke J. Saturday, P24 Military Deployment and Risk For Multiple Sclerosis In The First Gulf War. Poster presented at ACTRIMS meeting, June 1, 2013, Orlando, FL.
3 Confavreux C. An unchanging man faced with changing times. Brain. 2012 Jun;135(Pt 6):1663-5.