Written by Anthony Hardie, 91outcomes.com
(91outcomes.com) - Following on the heels of a presentation of new research findings by Dr. Dane Cook showing powerful objective evidence -- functional magnetic resonance imaging (fMRI) -- of dysfunction in the brains of ill veterans of the 1991 Gulf War, one of the pioneers in the field of Gulf War Illness research presented an overview of findings yesterday that both dovetailed with, and expanded on, Cook’s team’s fMRI findings.
Findings by a large research team led by Dr. Robert Haley, MD, of the University of Texas Southwestern Medical Center, added further confirmation of brain dysfunction in regards to pain processing, cognitive and other functioning in the brains of ill Gulf War veterans.
Using sophisticated medical research methods, including Quantitative Sensory Testing (QST) fMRI, a national survey of more than 8,000, and a week-long inpatient battery of advanced testing of nearly 100 ill Gulf War veterans, Haley’s team successfully to replicated, validated, and expanded on earlier findings that teased out the specifics of brain dysfunction in ill Gulf War veterans.
Haley’s team’s findings were presented during the first morning of two days of public meetings being held this week by the Congressionally chartered Research Advisory Committee on Gulf War Veterans’ Illnesses (RAC-GWVI) at the Boston University Medical Center in Boston, Mass.
(91outcomes.com) - Following on the heels of a presentation of new research findings by Dr. Dane Cook showing powerful objective evidence -- functional magnetic resonance imaging (fMRI) -- of dysfunction in the brains of ill veterans of the 1991 Gulf War, one of the pioneers in the field of Gulf War Illness research presented an overview of findings yesterday that both dovetailed with, and expanded on, Cook’s team’s fMRI findings.
Findings by a large research team led by Dr. Robert Haley, MD, of the University of Texas Southwestern Medical Center, added further confirmation of brain dysfunction in regards to pain processing, cognitive and other functioning in the brains of ill Gulf War veterans.
Using sophisticated medical research methods, including Quantitative Sensory Testing (QST) fMRI, a national survey of more than 8,000, and a week-long inpatient battery of advanced testing of nearly 100 ill Gulf War veterans, Haley’s team successfully to replicated, validated, and expanded on earlier findings that teased out the specifics of brain dysfunction in ill Gulf War veterans.
Haley’s team’s findings were presented during the first morning of two days of public meetings being held this week by the Congressionally chartered Research Advisory Committee on Gulf War Veterans’ Illnesses (RAC-GWVI) at the Boston University Medical Center in Boston, Mass.
Early Studies
In 1996, medical research findings from a UK scientist (Jamal et al) found a two-fold increase in cooling detection threshold in ill Gulf War veterans, providing some of the first objective evidence of the physiological underpinnings of Gulf War Illness.
Among the first research related to Gulf War veterans led by Haley was a 1998 medical research study that replicated the 1996 UK study. This was followed by several studies that looked at possible mechanisms of sensory and pain handling in the brains of ill Gulf War veterans. All showed objective evidence -- though sometimes difficult to interpret -- of brain dysfunction.
In 1996, medical research findings from a UK scientist (Jamal et al) found a two-fold increase in cooling detection threshold in ill Gulf War veterans, providing some of the first objective evidence of the physiological underpinnings of Gulf War Illness.
Among the first research related to Gulf War veterans led by Haley was a 1998 medical research study that replicated the 1996 UK study. This was followed by several studies that looked at possible mechanisms of sensory and pain handling in the brains of ill Gulf War veterans. All showed objective evidence -- though sometimes difficult to interpret -- of brain dysfunction.
One Syndrome, or Three?
Haley’s definition of Gulf War Illness is unique. Since the 1990s, he has postulated that there are subsets within Gulf War Illness, an idea that remains controversial today in the scientific community.
Haley’s three GWI subsets are:
Haley said he believes Syndrome 2 and 3 are related, and perhaps different stages of the same disorder, but that he believes Syndrome 1 is something very different from the other two.
However, another of the leading GWI medical researchers argued that the symptom subsets may instead be indvidualized manifestations of the same underlying disease processes.
Haley’s definition of Gulf War Illness is unique. Since the 1990s, he has postulated that there are subsets within Gulf War Illness, an idea that remains controversial today in the scientific community.
Haley’s three GWI subsets are:
- Syndrome 1: “Impaired Cognition,” a symptom complex characterized by inability to “remember things,” as well as profound fatigue.
- Syndrome 2: “Confusion-Ataxia”, a symptom complex that profoundly affects the veteran’s ability to think, comprehend, or interact.
- Syndrome 3: “Central Pain,” a symptom complex with chronic widespread pain as its central feature.
Haley said he believes Syndrome 2 and 3 are related, and perhaps different stages of the same disorder, but that he believes Syndrome 1 is something very different from the other two.
However, another of the leading GWI medical researchers argued that the symptom subsets may instead be indvidualized manifestations of the same underlying disease processes.
Pain Processing
Adding further confirmation to Cook’s team’s fMRI brain imagery related to pain processing, Haley reported that his team saw dramatically more sensitivity (hyperactivation/hyperarousal) with noxious heat pain stimuli in fMRI of Syndrome 1 and Syndrome 2 patients than in controls. However, the hyperactivation when exposed to noxious heat pain stimuli was inexplicably not present in fMRI of those labeled as Syndrome 3 (chronic pain).
His team found no difference in fMRI between controls and any of his three Syndromes when exposed to innocuous warm stimulation. However, the team’s findings in fMRI of Syndromes 1 and 2, which generally have little chronic pain, they had much less brain activation when exposed to innocuous warm stimulation than either controls or Syndrome 3, which is characterized by chronic pain.
Haley termed the effect in Syndrome 1 and Syndrome 2 of lower than normal pain sensitivity and brain activation to innocuous warm stimulation, but significantly higher than normal pain sensitivity and brain activation to noxious heat pain stimuli, “hypoactivity-hyperarousal” -- objective evidence of brain dysfunction in pain and other processing.
Different from Fibromyalgia
Haley’s fMRI and other findings differ from other studies of Fibromyalgia (FM) patients.
In FM, not only does fMRI reveal increased activation in the regions of the brain associated with pain processing when exposed to to noxious heat stimuli, but also to innocuous heat stimuli. This feeling that virtually everything is more painful than expected is known in medical terms as “allodynia”.
Brain Chemical Explanation
Haley’s research data suggested that the autonomic dysfunction affected one type of brain chemical effect -- cholinergic -- than another -- adrenergic.
Haley’s team’s findings found that all three Syndromes had higher scores than controls on the cholinergic symptom scales but not the adrenergic symptom scales.
Using another advanced testing procedure, QSART, differences were greater in the feet, less in shins and thighs, a pattern that is typical in peripheral nerve involvement. Haley said this is suggestive that small cholinergic fibers may be dysfunctioning.
In a study led by Dr. Gail Tillman (et al, 2012), testing of auditory stimuli in fEEG protocol found abnormal functioning of the cholinergic inhibitory (filtering), or “gating of ascending sensory impulses in the RAS of the brainstem.”
Of note, several other GWI studies have found abnormalities of cholinergic brain function, others have also found abnormalities in the brainstem of Gulf War veterans with GWI, and important theories of chronic pain involve abnormalities in “gating.”
Haley has long argued that even low-level exposure to chemicals -- including organophosphate (OP) pesticides and sarin nerve agent released at the Khamisiyah ammo dump detonations by U.S. troops in southeastern Iraq in March 1991 -- are the root cause of the brain damage and resulting disease state of ill Gulf War veterans.
Conclusions
Dr. Haley stressed the need to learn the underlying mechanisms of the disease. He said there is hope in the scientific commmunity that as with other diseases, trial and error may lead to effective treatments. However, he stressed the need to more precisely understand the underlying pathobiology, becuase, he said, “if we don’t stumble on a treatment, we are going to need to find one.”
He also stressed the need for a relatively quick diagnostic test to determine if veterans have GWI, or something else. As have other medical researchers, he noted that this is important not only for benefits purposes and peace of mind, but also for treatment purposes and potentially in the future to help validate the effectiveness of treatment.
*****
Additional Sources:
Jamal et al 1996, finding two-fol increase in cooling detection threshold during QST in British GWI GWVs.
1998 Haley study UT-S confirmed Jamal, then undertook several studies of possible mechanisms of sensory and pain handling.
Haley et al 2009. Infused physostigmine, found “abnormal brain response to cholinergic challenge in chronic encephalopathy from the 1991 Gulf War”.
Li et al, 2008. Hippocampal dysfunction in Gulf War veterans: investigation with ASL perfusion MRI and physostigmine challenge.
Tillman G et al, 2012. Auditory stimuli in fEEG protocol.
Adding further confirmation to Cook’s team’s fMRI brain imagery related to pain processing, Haley reported that his team saw dramatically more sensitivity (hyperactivation/hyperarousal) with noxious heat pain stimuli in fMRI of Syndrome 1 and Syndrome 2 patients than in controls. However, the hyperactivation when exposed to noxious heat pain stimuli was inexplicably not present in fMRI of those labeled as Syndrome 3 (chronic pain).
His team found no difference in fMRI between controls and any of his three Syndromes when exposed to innocuous warm stimulation. However, the team’s findings in fMRI of Syndromes 1 and 2, which generally have little chronic pain, they had much less brain activation when exposed to innocuous warm stimulation than either controls or Syndrome 3, which is characterized by chronic pain.
Haley termed the effect in Syndrome 1 and Syndrome 2 of lower than normal pain sensitivity and brain activation to innocuous warm stimulation, but significantly higher than normal pain sensitivity and brain activation to noxious heat pain stimuli, “hypoactivity-hyperarousal” -- objective evidence of brain dysfunction in pain and other processing.
Different from Fibromyalgia
Haley’s fMRI and other findings differ from other studies of Fibromyalgia (FM) patients.
In FM, not only does fMRI reveal increased activation in the regions of the brain associated with pain processing when exposed to to noxious heat stimuli, but also to innocuous heat stimuli. This feeling that virtually everything is more painful than expected is known in medical terms as “allodynia”.
Brain Chemical Explanation
Haley’s research data suggested that the autonomic dysfunction affected one type of brain chemical effect -- cholinergic -- than another -- adrenergic.
Haley’s team’s findings found that all three Syndromes had higher scores than controls on the cholinergic symptom scales but not the adrenergic symptom scales.
Using another advanced testing procedure, QSART, differences were greater in the feet, less in shins and thighs, a pattern that is typical in peripheral nerve involvement. Haley said this is suggestive that small cholinergic fibers may be dysfunctioning.
In a study led by Dr. Gail Tillman (et al, 2012), testing of auditory stimuli in fEEG protocol found abnormal functioning of the cholinergic inhibitory (filtering), or “gating of ascending sensory impulses in the RAS of the brainstem.”
Of note, several other GWI studies have found abnormalities of cholinergic brain function, others have also found abnormalities in the brainstem of Gulf War veterans with GWI, and important theories of chronic pain involve abnormalities in “gating.”
Haley has long argued that even low-level exposure to chemicals -- including organophosphate (OP) pesticides and sarin nerve agent released at the Khamisiyah ammo dump detonations by U.S. troops in southeastern Iraq in March 1991 -- are the root cause of the brain damage and resulting disease state of ill Gulf War veterans.
Conclusions
Dr. Haley stressed the need to learn the underlying mechanisms of the disease. He said there is hope in the scientific commmunity that as with other diseases, trial and error may lead to effective treatments. However, he stressed the need to more precisely understand the underlying pathobiology, becuase, he said, “if we don’t stumble on a treatment, we are going to need to find one.”
He also stressed the need for a relatively quick diagnostic test to determine if veterans have GWI, or something else. As have other medical researchers, he noted that this is important not only for benefits purposes and peace of mind, but also for treatment purposes and potentially in the future to help validate the effectiveness of treatment.
*****
Additional Sources:
Jamal et al 1996, finding two-fol increase in cooling detection threshold during QST in British GWI GWVs.
1998 Haley study UT-S confirmed Jamal, then undertook several studies of possible mechanisms of sensory and pain handling.
Haley et al 2009. Infused physostigmine, found “abnormal brain response to cholinergic challenge in chronic encephalopathy from the 1991 Gulf War”.
Li et al, 2008. Hippocampal dysfunction in Gulf War veterans: investigation with ASL perfusion MRI and physostigmine challenge.
Tillman G et al, 2012. Auditory stimuli in fEEG protocol.
1 comment:
Many thanks for providing this information from the meetings. I simply cannot wake up early enough to follow the meetings via phone.
Yet again more definitive research information is presented that the VA will continue to ignore and fail to disseminate to it's caregivers.
With tests confirming brain damage it should be easier to confirm the cause of such damage. I hope this answer comes soon and prompts the VA machine to move towards helping Gulf War veterans.
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