Kimberly Sullivan, PhD
Research Assistant
Professor, Department of Environmental Health
Boston University
School of Public Health
Former Associate
Scientific Director
VA Research Advisory
Committee on Gulf War Veterans’ Illnesses
On this week marking the 25th anniversary of the
Gulf War, I would like to express my concern and disappointment with the
conclusions from the recent volume 10 Institute of Medicine Gulf War Report and
highlight some of the important research that is ongoing in this field.
Gulf War Illness
GWI is a constellation of chronic health symptoms including
fatigue, pain, headaches, gastrointestinal and cognitive problems. It is a
multi-system disorder meaning that it affects not only the central nervous
system but also the immune and gastrointestinal systems. It affects about a
third of the nearly 700,000 veterans deployed to the war.
Gulf War Illness as a
Functional Disorder
The IOM report goes to great length to describe GWI as a
self-reported symptom based disorder for which there are no current objective
biomarkers and therefore it must be a ‘functional disorder’ meaning it has no
physical cause. The report describes it to be similar to other well accepted
symptom based disorders including post-traumatic stress disorder (PTSD). In
fact, this report places PTSD as the only disorder that has ‘sufficient evidence
of causal association’ to deployment to the Gulf War while it places GWI in the
second category of ‘sufficient evidence of an association’ to deployment to the
Gulf War.
However, less than 10% of GW veterans have been diagnosed
with PTSD and more than 30% have been diagnosed with GWI. In addition, it is
completely unclear why GWI is not also causally-related to deployment to the
war when both disorders are diagnosed the same way – by self-report of chronic
health symptoms.
The report also stresses that the health conditions
associated with Gulf War deployment are primarily mental health disorders and
functional medical disorders and that these associations emphasize the
interconnectedness of the brain and body.
However, the
brain and body are interconnected in GWI not because this is a stress-related
disorder without a unifying pathobiological cause as the IOM report suggests,
but rather because they are all part of the brain and immune pathways that are
activated as part of the neuroinflammatory response to pesticide and nerve
agent exposures. These chemicals directly target the nervous system and cause
inflammation. These pathways start by activating the immune cells in the brain
called microglia that release chemical messengers called cytokines in the brain
and the many body systems that are affected in GWI. Activating these inflammatory
systems in the brain and throughout the body can result in chronic symptoms
such as joint and muscle pain, memory problems, fatigue, headaches, and
gastrointestinal distress—all symptoms found in GWI. Researchers call this type
of chronic condition a post-inflammatory brain syndrome.
In fact, a paper
by Gulf War researchers from the Centers for Disease Control (CDC) recently showed
that Gulf War-relevant pesticides and nerve agents produced a neuroinflammatory
response resulting in hundreds-fold higher cytokine chemical signaling in a GWI
animal model. Preliminary studies in veterans with GWI suggest increased cytokine
levels that correlate with GWI symptoms as well.
Treatment focus for Veterans with GWI
The IOM report has concluded that research efforts should be
realigned to focus on the treatment and ‘management’ of Gulf War illness rather
than its causes. However, biological targets focused on neuroinflammatory
markers described above provide tangible and targeted treatment strategies for
GWI. Researchers at Boston University, Nova Southeastern University and VA
medical centers in Boston, Bronx and Miami are currently assessing the
effectiveness of targeted treatment trials using intranasal insulin,
D-cycloserine and Co-enzyme Q10 to treat the constellation of symptoms in GWI
including cognitive, fatigue and pain symptoms. Clinical researchers can do
better for our veterans than ‘manage’ their symptoms as the IOM suggests and the
research community is hopeful that these currently funded treatments will
provide much needed symptom relief for ill Gulf War veterans.
Brain Cancer Association
with Gulf War Service
The IOM report also states that the results of two published
VA studies reporting significantly increased brain cancer mortality rates found
in GW veterans who were in close proximity to the Khamisiyah weapons depot
detonations where large stores of sarin/cyclosarin were destroyed cannot be
trusted because the exposure plume modelling done to determine who was exposed
may be inaccurate. However, inaccuracies
in exposure modeling often make the analysis less sensitive rather than more
sensitive to finding differences between groups. Therefore, finding a 2 and 3
fold increase in brain cancer deaths in sarin exposed GW veterans suggests that
these rates are likely an underestimate of effect rather than an overestimate
of the effect of sarin exposure on brain cancer mortality in GW veterans.
Conclusion
The IOM report has
downplayed the importance of continuing to research the remaining questions in
GWI including identifying biomarkers of current illness, prior neutoxicant
exposures and targeted treatment strategies. This work is critically important
to Gulf War veterans who suffer from chronic health effects from these toxicant
exposures but also for many others including those who are occupationally
exposed to pesticides, including farmers and pesticide applicators around the
world. Gulf War veterans are counting on researchers to identify the cause and
pathobiology of their debilitating illness, and to identify treatments that
will work to improve all of their symptoms, not just manage them.
Most importantly, the end result of this report is that GW
veterans suffering from brain cancer or family members of those who have already
succumbed to brain cancer will not receive VA benefits now or likely ever for
their service-related mortality. These veterans have been forced to fight for
benefits while they are fighting for their lives. These veterans should be
given the benefit of the doubt in providing them with VA service connection for
this service-related mortality.
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