WRIISC-CA research update

WRIISC-CAClinical Experience with Gulf War One Veterans and their SymptomsJ. Wesson Ashford, MD, PhD

Director of California SiteWar-Related Injuries and Illnesses Study Center (WRIISC)

Palo Alto VA Health Care System wes.ashford@va.gov

June 26, 2013

Office of Public Health &Environmental Hazards

Most Frequent Symptoms, Affected Systemsof Veterans from the First Gulf WarFrequency of Symptoms of 53,835 Participants in VA Registry (19921997)Symptoms PercentageFatigue 20.5Skin rash 18.4Headache 18.0Muscle and joint pain 16.8Loss of memory 14.0Shortness of breath 7.9Sleep disturbances 5.9SystemsMusculoskeletal and connective tissue 25.4Mental disorders 14.7Respiratory system 14.0Skin and subcutaneous tissue 13.4Digestive system 11.1Chest pain 3.5

SOURCE: Murphy et al., 1999GW VeteransNon-GW VeteransFibromyalgia 19.29.6P Forgetfulness, loss of memory

Some of these symptoms have been stable (muscle, join pain), but most have gotten progressively worse.

Veteran has 4 combat comrades who had similar problems.

Veteran has had TBI x 2 times, major - Fort Bragg, parachuting. Knocked unconscious for 5 -10 seconds (witnessed). Some dizziness, no other residual.

Findings in Gulf War Veterans with Multi-symptom ConditionsSomatic Medical Symptoms: pain, fatigue, GI, skin, pulmonary normal x-rays of jointsNeurological normal MRI scansabnormal SPECT (? Normal PET, autonomic?)Psychiatric -depression, cognitive complaints, sleep issuesneuropsychological dysfunction - borderlineWRIISC-CASince its creation in 2007, WRIISC-CA has evaluated over 200 complex referrals routed through Central Office from most States West of the Mississippi River (and all States West of the Rockies).

Of these referrals, 42% have been Veterans of the First Gulf War.

The largest single problem in the WRIISC referrals has been PAIN!!

In the WRIISC-CA program,Veterans of GWI had more pain andfatigue than Veterans of prior or laterdeployments.

(note this data from a CPRS analysis of 79 cases, percent adjusted for missing data)WRIISC number of Veterans WRIISC percentage of VeteransGroupPre-GWIGW1Post-GW1Pre-GWIGW1Post-GW1Type*N174121Diag_Pain1233167180761Diag_Fatique31751841241Diag_PTSD1432178278812Diag_TBI1121146551672Diag_GI1017105941482Diag_Derm91065324292Diag_Sleep1227137166623Diag_Cog91885344383Diag_Pulmonary4932422143*1 = GWI MOST 2 = GWI LESS3 = AGE-relatedWRIISC CA Analysis of CPRS Data from Cases of 79 Deployed VeteransFUNDAMENTAL PROBLEMSGulf War Illness is considered to exist (Institute of Medicine, 2009)There have been many plausible theories for the unique constellation of symptoms that are frequently seen in the Veterans of the First Gulf War, but none has yielded an acceptable explanationThere is no clear relation to chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, etc.

Idiopathic Small Fiber Neuropathy(an example of a plausible theory)Caused by diabetes, HIV, Erythromelalgia, postherpetic neuralgia, CRPS, alcoholism, and many other nerve pain conditions Cause is also commonly idiopathicThere are no known causes for most cases and most tests do not identify itPeripheral nerve fibers that can be affected include peripheral autonomic neurons (acetylcholine, epinephrine), pain fibers (substance P) (like causalgia)Central small nerve fibers could also be affected (acetylcholine, norepinephrine, serotonin, others)

Plausible biological explanations for GW1 small nerve fiber damagePeripherally acting Anti-cholinesterase agents (Pyridostigmine bromide -PB, insecticides, DEET, permethryn, flea collar stories, sarin exposure, combinations), could increase the production of the enzyme acetyl-cholinersterase (AChEase). AChEase elevations (after stopping exposure and returning from conflict) could lead to a crisis related to low acetylcholine levels and an increase production of nerve-growth factor (NGF), leading to growth of pain-perception and various autonomic fibers, resulting in a chronic state of hyper-algesia (without evidence of joint or other system damage), along with chronic GI disturbances. (Note that Alzheimer patients who have withdrawn from chronic treatment with a similar agent, donepezil, frequently have precipitous declines. Further NGF treatment of Alzheimer patients led to a hyper-algesic state).Spider Bites toxin, not infectious agent, but a biological toxin that could damage small neurons.High temperatures may increase sensitivity of small neurons (heat-shock proteins).RADAR (radio-frequency injury to neurons has extensive literature, not considered a problem under normal circumstances, but there was a tremendous amount of radar in use in the First Gulf War). Immunological response chronic response to infectious agent attacking small neurons (like Guillan-Barre syndrome)Reaction of body to severe diarrhea or agent that caused severe diarrhea (local fruits, vegetables given to soldiers deployed early, those soldiers deployed later did not seem to get the condition).(Note, some diarrhea could have been an indication of sensitivity to PB tablets.)

Complex Exposures Can Affect Large Groups and Lead to a Unique Variety of Conditions, Symptoms and Disorders.

In Wars, many Individuals are exposed to a vast array of environmental, physical, and psychological stressors, with each conflict associated with its own unique set of problems (see Strauss, Lancet, 1999).

Consider that there are many exposures and other factors that lead combat Veterans to have a higher incidence of a particular variety of symptoms. Those symptoms may result from a multitude of causes. Further, each conflict, having different exposures, may induce a different constellation of symptoms.

In all cases, treatments must address the symptoms of the Veterans, minimize their discomfort, and maximize their function.Chronic Multi-symptom Illness Gulf War One TypeReferences1.Murphy FM, Kang H, Dalager NA, et al.: The health status of Gulf War veterans: lessons learned from the Department of Veterans Affairs Health Registry. Mil Med. 164(5), 327-31 (1999).2.Iowa Persian Gulf Study Group: Self-reported illness and health status among Gulf War veterans. A population-based study. The Iowa Persian Gulf Study Group. JAMA. 277(3), 238-45 (1997).3. Straus SE. Bridging the gulf in war syndromes. Lancet. Jan 16;353(9148):162-3 (1999).