Gulf
War Syndrome
Amato AA, McVey A, Cha C, Matthews EC, Jackson CE, Kleingunther R, Worley L, Cornman E, Kagan-Hallet K. Evaluation of neuromuscular symptoms in veterans of the Persian Gulf War. Neurology 1997; 48(1): 4-12.
Abstract: OBJECTIVE: To comprehensively evaluate complaints of muscle fatigue, weakness, and myalgias in Persian Gulf veterans (PGV). BACKGROUND: Approximately 700,000 American troops were deployed to the Persian Gulf during Desert Shield and Desert Storm. Upon return from the Gulf, some PGV developed unexplained illnesses, and special referral centers were established for the evaluation of these patients. Among the most common symptoms of these PGV are fatigue, weakness, and myalgias. An Institute of Medicine committee recommended further exploration into the possible etiologies of these complaints. METHODS: Twenty PGV with severe muscle fatigue, weakness, or myalgias that interfered with their daily activities were referred for an extensive prospective neuromuscular evaluation. Routine laboratory studies included serum creatine kinase (CK), erythrocyte sedimentation rate, thyroid function tests, and exercise forearm tests. All patients received nerve conduction studies (NCS), repetitive nerve stimulation, quantitative and single-fiber electromyography (EMG), and muscle biopsies. RESULTS: Manual muscle strength examinations were normal in all patients. Six patients had mildly elevated CKs (range 223 to 768 IU/l); otherwise, laboratory tests were unremarkable. NCS were normal except in 2 patients with carpal tunnel syndrome. Quantitative EMGs were normal. One patient had mildly increased jitter on single-fiber EMG. Muscle biopsies demonstrated minor nonspecific abnormalities in 5 patients (i.e., increased central nuclei, rare necrotic fibers, tubular aggregates). CONCLUSIONS: Despite severe subjective symptoms, most of our patients had no objective evidence of neuromuscular disease. Mildly increased CKs or nonspecific histologic abnormalities on muscle biopsy were evident in 8 patients but were not believed to be clinically significant in most. We found no evidence of a specific neuromuscular disorder in any patient. Exposures to toxins during the Persian Gulf War were not likely responsible for our patients' symptoms.
Amato AA. Identification of Gulf War syndrome: methodological issues and medical illnesses. Journal of the American Medical Association 1997; 278(5): 384-5.
Axelrod BN, Milner IB. Neuropsychological findings in a sample of Operation Desert Storm veterans. Journal of Neuropsychiatry and Clinical Neurosciences 1997; 9(1): 23-28.
Abstract: In response to ongoing complaints of memory, attention, and problem-solving difficulties among veterans of Operation Desert Storm and Shield (ODSS), a sample of 44 male veterans of ODSS underwent a comprehensive neuropsychological evaluation. Deficits relative to normative data were observed only on finger dexterity (Grooved Pegboard, bilaterally) and the Stroop Color and Word Test. Those with impaired Pegboard performance had lower performance on other tasks requiring psychomotor speed. Those with impaired Stroop had significantly lower motor and set-shifting performance. Scores of both impaired groups were higher on many clinical and supplemental scales of the MMPI. Despite subjective cognitive complaints reported in 39% of the overall sample, veterans with cognitive complaints differed from their peers primarily in greater psychological distress as depicted on the MMPI. The data are presented as preliminary clinical findings.
Baker DG, Mendenhall CL, Simbartl LA, Magan LK, Steinberg JL. Relationship between posttraumatic stress disorder and self-reported physical symptoms in Persian Gulf War veterans. Archives of Internal Medicine 1997; 157(18): 2076-2078.
Abstract: BACKGROUND: While prior studies show that combat veterans with posttraumatic stress disorder (PTSD) report more physical symptoms than veterans without PTSD, the link between PTSD and somatic complaints in Persian Gulf War veterans (PGWVs) is yet to be evaluated. METHODS: A questionnaire booklet was completed by 188 PGWVs, of whom half were patients in a veterans health screening clinic and half were non-treatment-seeking volunteers on active duty. The booklet included the Combat Exposure Scale, the Mississippi Post-Traumatic Stress Disorder Scale (MPTSD), and a subjective symptom-based health questionnaire. RESULTS: The 24 PGWVs (12.8%) with PTSD (MPTSD score > or = 116) reported more combat exposure (P = .02) and a greater number of physical symptoms (P = .001) than other PGWVs. Fatigue, nausea, muscle aches, dizziness, back pain, stomach ache, and numbness were much more likely to be reported by those with PTSD (MPTSD score > or = 116) than by those without PTSD (MPTSD score
Beale P. Gulf war illness. British Medical Journal 1997; 314(7086): 1041.
Brown TM, Fleishman SA, Casanova MF. Gulf war syndrome: polysomnographic study of eight cases. Journal of Chronic Fatigue Syndrome 1996; 2(1): 41-51.
Abstract: Our purpose was to explore whether patients complaining of the "Gulf War Syndrome" might have hidden sleep disorders, or psychiatric disorders, similar to what has been described in patients with chronic fatigue syndrome and fibromyalgia. Eight consecutive Gulf War veterans from the VA Gulf War Registry and Evaluation program complaining of fatigue, as well as other symptoms, were psychiatrically and polysomnograhically screened. One was found to have major depression and Post-traumatic Stress Disorder (PTSD), while another had PTSD alone. The sleep diagnoses assigned to the 8 patients were as follows: Three had sleep apnea syndrome, one of whom also had periodic limb movements of sleep disorder. Four others met criteria for periodic limb movements (PLMs) of sleep disorder. Four of the patients had clinically significant sleep state-misperceptions. All of the patients' symptoms were reported as occurring subsequent to Gulf War deployment, and not prior to deployment. As with the classic fatigue syndromes such as chronic fatigue syndrome and fibromyalgia, Gulf War Syndrome patients may benefit from a more thorough investigation of their sleep and psychiatric status. In view of these findings, consideration of polysomnograhic screening would appear appropriate in Gulf War Veterans with fatigue or sleep-related complaints.
Carnall D. Britain investigates the Gulf War Syndrome. British Medical Journal 1997; 312(7027): 332-333.
Currie E. The gulf war syndrome [Letter]. British Medical Journal 1995; 310(6990): 1334-35.
David A, Ferry S, Wessely S. Gulf war illness [Editorial]. British Medical Journal 1997; 314(7076): 239-40.
Editorial Bridging the Gulf [Editorial]. Lancet 1996 347(8998): 341.
Engel CC. Identification of Gulf War syndrome: methodological issues and medical illnesses. Journal of the American Medical Association 1997; 278(5): 383-84.
Fiedler N, Kipen H, Natelson B, Ottenweller J. Chemical sensitivities and the gulf war: department of veterans affairs research center in basic and clinical science studies of environmental hazards. Regulatory Toxicology and Pharmacology 1996; 24(1): S129-S138.
Abstract: The purpose of the New Jersey Center for Environmental Hazards Research is to define the illness referred to as Persian Gulf Syndrome (PGS). Our preliminary data indicated that more than half of the Persian Gulf Registry (PGR) veterans reported illness characterized by severe fatigue and symptoms consistent with chemical sensitivities. Therefore, our research approach focuses on investigations of veterans with chronic fatigue syndrome (CFS) and multiple chemical sensitivities (MCS). Project 1 is an epidemiological study of 2800 PGR veterans. Symptoms, indices of Chronic Fatigue (CF) and Chemical Sensitivity (CS), and risk factors will be surveyed with mailed questionnaires. Risk factors include demographics, past medical history, psychosocial variables, Gulf War experiences such as prophylactic medication use, occupational and environmental exposures, and pesticide exposures. Symptoms will be clustered to define Gulf War Syndromes. Significant associations between risk factors and these symptom clusters will also be investigated. Subjects identified as CF, CS, or both will be recruited into Projects 2 and 3. In Project 2, healthy veterans will be compared to veterans with CF, CS, and CF concurrent with CS. Veterans will undergo four studies: (1) viral-immunological, (2) psychiatric, psychological, behavioral, and neuropsychological, (3) autonomic dysregulation, and (4) marker of P4501A2 induction resulting from exposure to combusting material. The purpose of Project 3 is to test the autonomic, immunologic, neuropsychologic, and psychologic responses of veterans with CS or CF to two stressors: controlled chemical exposure and exercise. CS subjects will undergo chemical exposures in our Controlled Environment Facility (CEF) to assess their biologic and psychologic response to low-level exposure. CF subjects will undergo a maximal treadmill exercise test. Circadian patterns of catecholamines and axillary temperature, viral burden, and cardiovascular and endocrine reactivity will be measured in response to this physical stressor. Project 4 is an animal study evaluating the interaction between stress and pathology/physiology when rats are predisposed to disease by exposure to Soman or to Dioxin. Two strains of rats that differ in stress reactivity will be used to determine the interaction of hereditary factors and chemical exposure.
Gordon V. Identification of Gulf War syndrome: methodological issues and medical illnesses. Journal of the American Medical Association 1997; 278(5): 383.
Gots RE. Identification of Gulf War syndrome: methodological issues and medical illnesses. Journal of the American Medical Association 1997: 278(5): 385.
Haley RW. Is there a Gulf War Syndrome? Searching for syndromes by factor analysis of symptoms. Journal of the American Medical Association 1997; 277(3): 215-222.
Haley RW. Evaluation of neurologic function in Gulf War veterans. A blinded case-control study. Journal of the American Medical Association 1997; 277(3): 223-30.
Haley RW. Self-reported exposure to neurotoxic chemical combinations in the Gulf War. A cross-sectional epidemiology study. Journal of the American Medical Association 1997; 277(3): 231-237.
Heaf P. Gulf war illness. British Medical Journal 1997; 314(7086): 1041.
Hyams KC, Wignall FS, Roswell R. War syndromes and their evaluation: from the U.S. Civil War to the Persian Gulf War. Annals of Internal Medicine 1996; 125(5): 398-405.
Abstract: PURPOSE: To better understand the health problems of veterans of the Persian Gulf War by analyzing previous war-related illnesses and identifying possible unifying factors. DATA SOURCE: English-language articles and books on war-related illnesses published since 1863 that were located primarily through a manual search of bibliographies. DATA EXTRACTION: Publications were assessed for information on the clinical characteristics of war-related illnesses and the research methods used to evaluate such illnesses. DATA SYNTHESIS: Poorly understood war syndromes have been associated with armed conflicts at least since the U.S. Civil War. Although these syndromes have been characterized by similar symptoms (fatigue, shortness of breath, headache, sleep disturbance, forgetfulness, and impaired concentration), no single recurring illness that is unrelated to psychological stress is apparent. However, many types of illness were found among evaluated veterans, including well-defined medical and psychiatric conditions, acute combat stress reaction, post-traumatic stress disorder, and possibly the chronic fatigue syndrome. No single disease is apparent, but one unifying factor stands out: A unique population was intensely scrutinized after experiencing an exceptional, life-threatening set of exposures. As a result, research efforts to date have been unable to conclusively show causality, have been subject to reporting bias, and have lacked similar control populations. In addition to research limitations, war syndromes have involved fundamental, unanswered questions about the importance of chronic somatic symptoms and the factors that create a personal sense of ill health. CONCLUSION: Until we can better understand what constitutes health and illness in all adult populations, we risk repeated occurrences of unexplained symptoms among veterans after each war.
Hyams KC. Identification of Gulf War syndrome: methodological issues and medical illnesses. Journal of the American Medical Association 1997; 278(5): 384.
Jamal GA, Hansen S, Apartopoulos F, Peden A. The "Gulf War syndrome". Is there evidence of dysfunction in the nervous system? Journal of Neurology Neurosurgery and Psychiatry 1996; 60(4): 449-51.
Abstract: In a pilot study, 14 Gulf War veterans were randomly selected from a large list of those with unexplained illness, to compare the functional integrity of the peripheral and central nervous system with a group of 13 healthy civilian control subjects using predetermined outcome measures. The controls were matched closely for age, sex, handedness, and physical activity. Outcome measures included scoring of symptoms and clinical neurological signs, quantitative sensory testing of heat, cold and vibration sensibilities, motor and sensory nerve conduction studies on upper and lower limbs, needle EMG of distal and proximal muscles and multimodality evoked potential (visual, brainstem, and somatosensory) studies. Three measurements, all related to peripheral nerve function (cold threshold (P = 0.0002), sural nerve latency (P = 0.034), and median nerve sensory action potential (P = 0.030) were abnormal in the veterans compared with the controls. There may be a dysfunction in the veterans but more studies are required to investigate the findings further and to characterise the dysfunction if confirmed.
Kaires P. Identification of Gulf War syndrome: methodological issues and medical illnesses. Journal of the American Medical Association 1997; 278(5): 385-87.
Landrigan PJ. Illness in Gulf War veterans. Causes and consequences. Journal of the American Medical Association 1997; 277(3): 259-61.
Lo S, Buchholz CL, Wear DJ, Hohm RC, Marty AM. Histopathology and doxycycline treatment in a previously healthy non-AIDS patient systemically infected by Mycoplasma fermentans (incognitus) strain. Modern Pathology 1991; 6: 759-754.
Lo S, Dawson MS, Newton PB, Sonoda AA, Shih WK, Engler WF, Wang RY, Wear DJ. Association of the virus-like infectious agent originally reported in patients with AIDS with acute fatal disease in previously healthy non-AIDS patients. American Journal of Tropical Medicine and Hygiene 1989; 41: 364-376.
Lo S, Wear DJ, Shih Wk, Wang RY, Newton PB, Rodriguez JF. Fatal systemic infections of nonhuman primates by mycoplasma fermentans (incognitus strain). Clinical Infectious Diseases 1993; 17(Suppl 1): S283-S288.
Milner IB. Is there a Gulf War syndrome? Journal of the American Medical Association 1994; 271(9): 661.
Nicolson G. Doxycycline treatment and desert storm [Letter]. Journal of the American Medical Association 1995; 273(8): 618.
Nicolson GL, Nicolson NL, Nasralla M. Mycoplasmal infections and chronic fatigue illness (gulf war illness) associated with deployment to operation Desert Storm. International Journal of Medicine 1997; In Press.
Nicolson GL, Nicolson NL. Diagnosis and treatment of mycoplasmal infections in Persian Gulf War Illness - CFIDS patients. International Journal of Occupational, Medical and Immunological Toxicology 1996; 5: 69-78.
Nicolson GL, Nicolson NL. The eight myths of Operation 'Desert Storm' and Gulf War syndrome. Medicine, Conflict and Survival 1997; 13(2): 140-46.
Abstract: Several conventional claims regarding Gulf War Syndrome are criticized: that Gulf War veterans are no sicker than the civilian population as a whole; that Gulf War Syndrome is a myth invented by the press; that GWS cannot be defined as a legitimate medical syndrome; that since its cause cannot be determined, it is not a problem associated with Operation 'Desert Storm'; that the US and UK governments are doing all they can to investigate and treat illness in veterans or deny existence of over 100,000 cases in veterans and their families; that GWS will settle without treatment; that the armed forces were well prepared for integrated conflict involving chemical and biological warfare in the Middle East, increasing the risk of this in the future.
Nicolson GL. Chronic fatigue illness and Operation Desert Storm. Journal of Occupational and Environmental Medcine 1996; 38(1): 14-16.
Revell T. The gulf war syndrome [Letter]. British Medical Journal 1995; 310(6986): 1073.
Roberts J. US report denies that gulf war syndrome is disease. [Letter]. British Medical Journal 1995; 311(7002): 406.
Roberts J. New U.S. theory on Gulf War Syndrome [Letter}. British Medical Journal 1996; 312(7038): 1058.
Roberts J. U.S. responds to new suggestion of Gulf War Syndrome [Letter]. British Medical Journal 1996; 312(7047): 1629.
Roberts J. Chemical weapons did not cause the gulf war syndrome [Letter]. British Medical Journal 1995; 310(6981): 692.
Roberts J. Gulf War syndrome needs coordinated study [Letter]. British Medical Journal 1995; 310(6972): 77.
Roberts J. Debate over US gulf war syndrome continues. [Letter]. British Medical Journal 1994; 309(6966): 1392-93.
Robinson A. Veterans worry that unexplained medical problems a legacy of service during Gulf War. Canadian Medical Association Journal 1995; 152(6): 944-47.
Abstract: Some Canadians who served in the military in the Persian Gulf 4 years ago complain of a range of symptoms commonly described as Gulf War syndrome. Although the syndrome is not recognized as a clinical entity, symptoms include fatigue, lack of sleep, depression, cognitive problems, rashes, bone aches, lassitude, lack of motivation, forgetfulness, mood changes irritability and diarrhea. The medical branch of the Department of National Defence has established programs to inform, guide diagnosis and reach out to symptomatic veterans of the Persian Gulf conflict. Civilian physicians who provide similar care to military personnel who participated in the conflict are invited to call the medical branch (613 996-3752) for further information.
Rook GA, Zumla A. Gulf War syndrome: is it due to a systemic shift in cytokine balance towards a Th2 profile? Lancet 1997; 349(9068): 1831-33.
Abstract: The symptoms of Gulf War syndrome are compatible with the hypothesis that the immune system of affected individuals is biased towards a Th2-cytokine pattern. Factors that could lead to a Th2 shift among Gulf War veterans include exposure to multiple Th2-inducing vaccinations under stressful circumstances and the way in which such vaccinations were administered, which would be expected to maximise Th2 immunogenicity. These factors may have led to a long-term systemic shift towards a Th2-cytokine balance and to mood changes related to the immunoendocrine state. Other vaccines that lead to similar long-term, non-specific shifts in cytokine balance are well-established. If our hypothesis is proven, treatment may be possible with regimens that induce a systemic Th1 bias.
Schlesinger N. Identification of Gulf War syndrome: methodological issues and medical illnesses. Journal of the American Medical Association 1997; 278(5): 383.
Sillanpaa MC, Agar LM, Milner IB, Podany EC, Axelrod BN, Brown GG. Gulf War veterans: a neuropsychological examination. Journal of Clinical and Experimental Neuropsychology 1997; 19(2): 211-19.
Abstract: Eighty-two Persian Gulf War veterans seen in clinic were referred for neuropsychological evaluation. Relatedness of neuropsychological and neurological functioning to subjective complaint, exposure, a clinical signs index, and possible interference variables was examined in a subsample of 49 who completed assessment. The subsample was representative of the entire group with respect to symptom severity. Variables representing sustained attention, grip strength, motor coordination, vibratory sense, finger-tip number writing perception, executive functioning, memory functioning, and subjective complaint were considered. Neuropsychological performance appeared to be more related to emotional functioning than demographic variables or variables associated with the war. Individual differences may be contributing to different emotional reactions to illnesses, perceptions of exposure risks and cognitive functioning, and responses to stress.
Stretch RH, Bliese PD, Marlowe DH, Wright KM, Knudson KH, Hoover CH. Physical health symptomatology of Gulf War-era service personnel from the states of Pennsylvania and Hawaii. Military Medicine 1995; 160(3): 131-36.
Abstract: We present data on physical health and possible "Gulf War syndrome" from a Congressionally mandated study of over 4,000 active duty and reserve service members from the states of Hawaii and Pennsylvania who served during Operation Desert Storm. We found that deployed veterans report significantly more physical health symptoms than non-deployed veterans that cannot be explained by reasons other than deployment alone. We also identified a subgroup of 178 deployed veterans at risk for possible Gulf War syndrome. We recommend that services collect baseline information from units likely to deploy in the future and update that information regularly.
Taylor-Robinson D. Infections due to species of mycoplasma and ureplasma: an update. Clinical Infectious Diseases 1996; 23: 671-682.
The Iowa Persian Gulf Study Group. Self-reported illness and health status among Gulf War veterans. A population-based study. Journal of the American Medical Association 1997; 277(3): 238-245.
Wittich AC. Gynecologic evaluation of the first female soldiers enrolled in the Gulf War comprehensive clinical evaluation program at Tripler Army Medical Center. Military Medicine 1996; 161(11): 635-37.
Abstract: Tripler Army Medical Center initiated the Department of Defense's Persian Gulf Illness Comprehensive Clinical Evaluation Program (CCEP) on June 15, 1994. In the first 5 months, 100 patients enrolled in this program. Sixteen (16%) were women who served in the Persian Gulf during Desert Shield/ Desert Storm, and 1 (1%) was the dependent wife of a Gulf War veteran who is experiencing illness that may be related to the Persian Gulf War. All 17 women enrolled in the CCEP were evaluated in the Tripler Army Medical Center Obstetrics and Gynecology Clinic between June 17 and November 10, 1994. Each patient underwent gynecologic history, pelvic exam, Pap smear, and screen for fecal occult blood. Ten patients underwent baseline mammograms and 13 patients underwent urogenital and cervical cultures for aerobic bacteria, chlamydia and herpes simplex. The 1 patient with an abnormal Pap smear underwent cervical and endocervical biopsies and colposcopy (histology demonstrated no dysplasia or neoplasia). Half of the 16 Gulf War veterans experienced gynecologic problems while serving in the Gulf and 43% admitted gynecologic problems since returning in 1991. Of 6 patients who became pregnant after returning, 5 had normal pregnancies and 1 suffered four miscarriages.