WASHINGTON — While veterans serving in the military during the Gulf War era (GWE) appear to have higher risk for multiple sclerosis and a range of neurological illnesses, little has been documented previously on prevalent types of MS or other clinical features.
That’s why a study team from the VA’s Multiple Sclerosis Center of Excellence (MSCoE) set out to determine clinical features at diagnosis for a large nationwide incident cohort of MS patients who are GWE veterans.
Results, published in recently in the journal Acta Neurologica Scandinavica, were based on VA medical records and databases for cases of MS with onset in or after 1990, active duty between 1990 and 2007 and service connection by the VA. Those files were reviewed for diagnosis and demographic variables, with neurological involvement summarized by the Kurtzke Disability Status Scale (DSS) and the Multiple Sclerosis Severity Score (MSSS).
Relapsing-remitting MS was by far the most common; among 1,919 cases of clinically definite MS, 94% had RRMS, with 6% initially diagnosed with primary progressive MS (PPMS). PPMS, characterized by worsening neurologic function, was more common in males of all races, as well as blacks of both sexes, according to the results.
“In this incident cohort, males and blacks had significantly higher proportions of primary progressive MS,” explained lead author Mitchell T. Wallin, MD, MPH, in an article published on the VA’s MS Centers for Excellence website. “MS disability at diagnosis was significantly more severe in blacks and significantly less so in whites and in women vs. men. The MS Severity Score, a disability measure that accounts for time with MS, was marginally greater in black males and other males compared to the other sex-race groups. This morbidity assessment early in the course of MS provides population-based data for diagnosis, management, and prognosis.”
The researchers also found that, at diagnosis, functional system involvement was:
- pyramidal 69%,
- cerebellar 58%,
- sensory 55%,
- brainstem 45%,
- bowel/bladder 23%,
- cerebral 23%,
- visual 18%, and
- other 5%.
Mean DSS scores were calculated as the following: white males, females 2.9, 2.7; black males, females 3.3, 2.8; and other-race males, females 3.2, 2.6.
“Mean and median MSSS were marginally greater in black males and other males compared to the other sex-race groups,” the researchers pointed out.
Questions Remain
Why MS—as well as other brain disorders such as amyotrophic lateral sclerosis, Parkinson’s disease and brain cancer—is more prevalent in GWE veterans remains an open question. Also puzzling to researchers is the difference in MS rates among the military services, as well as racial differences in severity.
“We do know that, in general, environmental risk factors, such as smoking and vitamin D insufficiency, as well as genetic risk factors, contribute to the onset of MS,” wrote Wallin, who is director for the MSCoE-East. “What we will be exploring in more detail is this relationship to minority populations and branch of service. This Gulf War era military MS cohort, like prior cohorts, provides a unique resource for further study that can lead to better understanding and hopefully improved treatments.”
Wallin led a study in 2012 indicating 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 actually deployed in the Gulf War.2
“We found that there was no increase in risk across the board for any group in Gulf War I,” Wallin told U.S. Medicine at the time. “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.”
He said that looking for risk factors in deployment seemed like a logical next step for research, since “those deployed in theater had exposures including viral infections, vaccines, air pollutants and central nervous system toxins. Could those exposures have triggered MS?” But nothing obvious was identified as a cause.
In some ways, epidemiological studies have only added to the mystery. Research published recently in Medical Surveillance Monthly Report noted how much incidence rates varied across the services. For example, the Air Force had the highest rate at 20.3 per 100,000, which was 2.2 times higher than the lowest service, the Marines, which had a rate of 9.3 per 100,000. The Navy’s rate was 13.3 per 100,000, and the Army had a rate of 14.6 per 100,000. The reserve/guard component, meanwhile, had an overall rate of 6.9 cases per 100,000.
In addition, officers had 50% higher rates than enlisted members, 9.7 vs. 6.4 per 100,000, respectively. Another notable finding was that military healthcare workers had nearly triple the rate of servicemembers in combat-specific occupations, 11.4 vs. 4.0 per 100,000.
While not necessarily providing answers about MS causes, the study did include some positive news: From 2007 to 2016, the unadjusted incidence rates of MS declined 25.4% among active component servicemembers. Active duty females had a much higher rate of new diagnoses than men throughout the study period but also experienced a significantly sharper decline in incidence rates.
Annual rates of new MS diagnoses for women sharply declined 43.2% during the study period but just 16.6% for men. The plummet in rates for women significantly changed the difference in the rate of diagnoses between women and men. In 2007, 3.7 times as many women had incident diagnoses as men. By 2016, the sex incidence ratio had declined to 2.5. Rates among non-Hispanic black servicemembers fell 40.8% over the 10 years.
1Wallin MT, Culpepper WJ, Maloni H, Kurtzke JF. The Gulf War era multiple sclerosis cohort: 3. Early clinical features. Acta Neurol Scand. 2018 Jan;137(1):76-84. doi: 10.1111/ane.12810. Epub 2017 Aug 22. PubMed PMID: 28832890.
2Wallin 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
3Williams VF, Stahlman S, Ying S. Multiple Sclerosis Among Service Members of the Active and Reserve Components of the U.S. Armed Forces and Among Other Beneficiaries of the Military Health System, 2007-2016. MSMR. August 2017;24(8):2-11.