Brain–Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of (...), 2021, Steele, Klimas et al

[Wyva]

Abstract

The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990–1991 Gulf War.

The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S. sites that included clinical assessments, brain imaging, neuropsychological testing, and analyses of a broad range of immune and immunogenetic parameters. GWI cases were similar to controls on most demographic, military, and deployment characteristics although on average were two years younger, with a higher proportion of enlisted personnel vs. officers.

Results of physical evaluation and routine clinical lab tests were largely normal, with few differences between GWI cases and healthy controls. However, veterans with GWI scored significantly worse than controls on standardized assessments of general health, pain, fatigue, and sleep quality and had higher rates of diagnosed conditions that included hypertension, respiratory and sinus conditions, gastrointestinal conditions, and current or lifetime depression and post-traumatic stress disorder.

Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009). Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI. Data and samples from the GWIC project are now stored in a repository for use by GWI researchers.

Future reports will present detailed findings on brain structure and function, immune function, and association of neuroimmune measures with characteristics of GWI and Gulf War service.

Open access: https://www.mdpi.com/2076-3425/11/9/1132

 

[boolybooly]

I think the comparison of enlisted vs officer is an artefact of control group selection and should not be considered significant experimentally but is indicative of methodological bias.

The control group also seems a little small to me at 17% of subjects.

 

[Hutan]

Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009).
Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI.

Those are pretty interesting findings on a fairly good sized sample. I thought the incidence of tender points consistent with a diagnosis of fibromyalgia was interesting too. - although I don't know what the significance of tender points is.

Gulf War illness cases also reported significantly higher levels of pain on both their best and worst days and tested positive for a significantly greater number of fibromyalgia (FM) tender points than controls. Twenty-eight percent of GWI cases had 11 or more positive tender points out of 18 tested, consistent with 1990 diagnostic criteria for fibromyalgia [44], vs. only 2% of controls (p < 0.001).

It's worth noting for future comparisons with figures for ME/CFS that the lifetime or current incidence of major depression in the healthy controls was 24%.

I was surprised that they only looked for postural orthostatic hypotension (BP) and not for tachycardia (or ideally, evidence of cerebral hypo perfusion), especially given Nancy Klimas was part of the team.

Few veterans exhibited possible evidence of postural orthostatic hypotension when comparing diastolic and systolic blood pressure moving from laying down to a standing position, with no significant differences between GWI cases and controls.

 

[shak8]

Those are pretty interesting findings on a fairly good sized sample. I thought the incidence of tender points consistent with a diagnosis of fibromyalgia was interesting too. - although I don't know what the significance of tender points is.


It's worth noting for future comparisons with figures for ME/CFS that the lifetime or current incidence of major depression in the healthy controls was 24%.

I was surprised that they only looked for postural orthostatic hypotension (BP) and not for tachycardia (or ideally, evidence of cerebral hypo perfusion), especially given Nancy Klimas was part of the team.

Tender points as diagnostic aids are not present in the most current (2016) guide to diagnosing fibromyalgia, rather the number of areas of pain throughout the body is emphasized.

 

[Hutan]

Part of Table 4:


Nothing much survived the adjustment procedure, which seemed rather extensive (veterans’ age, rank, PTSD status, and significant deployment experiences/exposures) - just the mild brain trauma during deployment and the extended use of skin pesticides. But there are differences in quite a lot of measures. To me, it looks as though it would be possible to find data to support many ideas about how pesticides and immune stimulation might have played a role. Slicing and dicing the data in different ways might have given different answers. It would have been nice to see some charts.

For example - 'received one or more shots in arm in theatre' is differentiated from 'received one or more shots in buttocks in theatre'. I would have thought combining those, and perhaps also including immunisations immediately prior to deployment, might possibly have suggested immunisations were a significant factor. And combining the various exposures to pesticides might have been useful.

It's quite messy and difficult. I wonder what their future papers with more medical investigations will report.

This initial report from the full GWIC case-control study sample provides an overview of research assessments and general health comparisons between GWI cases and controls. Future papers will report on results of neuroimaging, neurocognitive, immune, and genetic testing from Gulf War veterans evaluated at the three GWIC clinical sites, including the degree to which identified health outcomes differ in GWI subgroups and are associated with exposures during the Gulf War.

It was nice to see a good level of respect for the difficulties the veterans with GWI have endured.

Improved understanding of brain and immune GWI pathobiology provided by the GWIC and related projects is essential for identifying effective treatments and valid diagnostic tests for the complex of serious health problems that continue to affect Gulf War veterans, 30 years after their service in Operation Desert Storm.

 

[Hutan]

Just by the way, Table 3 gives the list of symptoms, and they look awfully like ME/CFS to me. Here's just one domain , covering unrefreshing sleep, fatigue and something that could very easily be PEM.

 

[Mithriel]

After reading the comments in the NICE document I have become very aware of what researchers and doctors consider CFS or ME/CFS to be.

The only thing in the table that could be specific to ME is feeling unwell after exercise but while that could be PEM it could also be a way of describing heart disease or lung disease or even MS or RA.

Basically, they are describing a situation where fatigue is constant and debilitating and I now believe that this is exactly what doctors consider ME to be and why they think CFS is the better name with CFS/ME thrown in to appease the patients.

We are still in a situation where we suspect it could be ME but no one is asking the right questions to be certain. It is not far from diagnosing chronic fatigue by asking how often people use the lifts instead of climbing the stairs. We are forced to read between the lines of everything and it is just not right we should have to do it. The fact that many of us are so good at it has actually pushed the field forward and I admire the people who can do that.

Tender points as diagnostic aids are not present in the most current (2016) guide to diagnosing fibromyalgia, rather the number of areas of pain throughout the body is emphasized.

This is another point where the research and diagnosis is confused. If they are just looking at how many areas of pain there are, how is it possible to differentiate between fibromyalgia and the widespread pain of Myalgic (the clue is in the name) Encephalomyelitis. A doctor told me that at the Royal Free patients hit the roof when they were touched and I have been in pain in some part of my body constantly for over fifty years.

The association with fibro came when CFS was invented and now we have things like POTS added on, even "experts" in the UK claiming that PEM is another disease, instead of seeing widespread pain, dysautonomia and an abnormal reaction to exercise as intrinsic parts of the disease.

I am sick of this guessing game. On forums and within the charities (up to a point!) we know what ME does to you but it is time researchers and doctors had enough respect for us to accept we know more about what the disease is than they do.

 

[Hutan]

The only thing in the table that could be specific to ME is feeling unwell after exercise but while that could be PEM it could also be a way of describing heart disease or lung disease or even MS or RA.

I don't disagree with you that it's frustrating that researchers, and especially researchers deeply familiar with ME/CFS, don't better assess people with illnesses that look a lot like ME/CFS for PEM. They did however exclude people with other obvious reasons for multi-symptom illness. These reasons accounted for 35% of otherwise eligible veterans being excluded from the study.

Exclusionary conditions. The GWIC study eligibility criteria excluded veterans who had ever been diagnosed by a physician with multiple sclerosis, lupus, rheumatoid arthritis, stroke, Parkinson’s disease, amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), Alzheimer’s disease, bipolar disorder, or schizophrenia. Criteria also excluded veterans if they had previously been diagnosed with any of the following conditions and there was any indication the condition was still active in the five years before the study: seizure disorder, heart disease (high blood pressure or high cholesterol not exclusionary), kidney disease, liver disease, cancer (except non-melanoma skin cancer, which was not exclusionary). For example, veterans who had a prior cancer diagnosis but had been told by their providers that they had been cancer–free for at least 5 years were not excluded from the study. Veterans diagnosed with diabetes were included only if their blood sugar had been well controlled for at least 2 years but were otherwise excluded. Veterans were also excluded if they had a chronic infectious disease lasting six months or longer or were recovering from a serious injury that could account for their symptoms. In addition, veterans were excluded if they had been hospitalized for post-traumatic stress disorder, depression, or alcohol or drug dependence in the previous 5 years.

I am sick of this guessing game.

Me too. Researchers asking better questions would help, but I suspect that it's only when we have solid biomarkers that we'll really know how similar conditions relate to ME/CFS.

 

[Mithriel]

I agree with you, Hutan but it is the "feeling unwell after physical exertion" that gets to me especially. Surely they could have done better than that. Asking if there are times when there is a delay after exertion before feeling unwell would be very informative. It could hardly add to the cost of the trial to add another question and it makes me wonder if they know this often happens in ME.