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Gulf War Illness Linked to Cholinergic Abnormalities

Pauline Anderson

November 26, 2012

Medscape Medical News > Neurology

In the early 1990s, about 700,000 US troops were deployed to the Middle East to take part in a 5-week air bombing campaign and a 5-day ground operation that involved almost no traditional combat. Of these soldiers, about 150,000 subsequently became ill, almost all had to leave the service, and many remain unemployable, said Dr. Haley.

Dr. Robert W. Haley

Their illness is controversial; the US government has never acknowledged that Gulf War syndrome is a real illness, and many people still believe it's psychological, he said.

For this latest study, researchers randomly selected 8020 representative Gulf War veterans for detailed interviews and included 97 in the current study. Of these, 66 met the case definition of Gulf War illness that Dr. Haley and his colleagues had previously validated. These case veterans represented 3 forms of the illness included in that definition:

Syndrome 1 (mild cognitive impairment; 21 cases): These soldiers have difficulty thinking, concentrating, and remembering, and some have symptoms of depression.
Syndrome 2: (confusion-ataxia; 24 cases): Veterans with this form of the illness have balance problems and what Dr. Haley described as "early Alzheimer's disease that doesn't get worse" or chronic neurotoxic encephalopathy.
Syndrome 3 (central neuropathic pain; 21 cases): Soldiers with this syndrome describe having a constant pain between their shoulders and down their arms and thighs. They have difficulty riding in a car because of the pain, and nothing seems to relieve it, said Dr. Haley.
Also included in the study were 31 control veterans: 16 who were deployed but did not meet the case definition of Gulf War illness and 15 who were in the military but not deployed

The soldiers completed questionnaires and underwent a battery of standard tests to assess autonomic function and objective tests of autonomic dysfunction.

Symptom Score Elevations

The study found that in the various symptom domains of the Autonomic Symptom Profile (eg, orthostatic intolerance, sleep dysfunction, autonomic diarrhea, pupillomotor symptoms, sexual dysfunction), those with syndrome 2 had the highest scores, but the pattern of symptom score elevations was similar among all 3 syndrome groups.

On objective autonomic tests, those with Gulf War illness differed most from controls on the Quantitative Sudomotor Axon Reflex Test (for example, P ≤ .001 compared with controls for the foot). The degree of difference on this test was related to peripheral nerve length, typical of a length-dependent neuropathy of small-caliber, unmyelinated, peripheral nerve fibers, said the authors.

Veterans with syndrome 2 and 3 had a statistically significant increase in cooling detection threshold. This, said the authors, might also reflect underlying small-fiber impairment.

The Composite Autonomic Severity Score (CASS) varied significantly across the clinical groups (P = .045) and was higher in the syndrome 2 group than in the controls (P = .02).

Circadian Abnormality

Analysis of 24-hour electrocardiogram monitoring showed that high-frequency heart rate variability (HF HRV) increased normally at night in the control group but not in the 3 syndrome groups.

"Because peripheral vagal baroreflex function was not significantly impaired, this abnormality of circadian variation in HF HRV suggests dysfunction in the central nervous system control of parasympathetic outflow," the authors write. Impaired HF HRV was not explained by smoking, creatinine clearance, psychiatric comorbidity, diagnosis of heart disease, glycated hemoglobin level, body mass index, or medications.

During the day, HF HRV in veterans with syndrome 1 did not differ from controls but the syndrome 2 group had significantly lower HF HRV than controls. Those with syndrome 3 had significantly higher HF HRV than controls, particularly during the morning hours. .


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