Tag: Gulf War Illness

Chronic fatigue syndrome in male Gulf war veterans and civilians: a further test of the single syndrome hypothesis

Abstract:

Different modes of fatigue onset in male Gulf War veterans versus male civilians raise the possibility that chronic fatigue syndrome (CFS) may not be a single disease entity. We addressed this issue by comparing 45 male veterans with CFS to 84 male civilians who satisfied identical case criteria. All were evaluated for fibromyalgia (FM), multiple chemical sensitivity and psychiatric comorbidity. CFS was more likely to present in a sudden flu-like manner in civilians than veterans (p < .01) and comorbid FM was more prevalent in civilians (p < .01). These findings question the assumption that all patients with CFS suffer from the same underlying disorder.

 

Source: Ciccone DS, Weissman L, Natelson BH. Chronic fatigue syndrome in male Gulf war veterans and civilians: a further test of the single syndrome hypothesis. J Health Psychol. 2008 May;13(4):529-36. Doi: 10.1177/1359105308088525. https://www.ncbi.nlm.nih.gov/pubmed/18420761

 

Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins

Abstract:

This study examined 328 CFS sera in a study with 17 CCFP, 8 Gulf War Veterans (GWV), 24 Prostate Cancer (PC), and 52 normal sera in the modified Membrane Immunobead Assay (MIA) procedure for CTX. Three hundred and twenty-eight CFS patients’ sera were examined by the modified MIA with purified MAb-CTX and 91.2% gave a titre > or =1:40. 76% of the 17 CCFP sera samples and 100% of the 8 GWV sera samples also had a titre > or =1:40. 92.3% of 52 normal sera showed titres of 1:20 or less, while 4 gave titres of > or =1:40.

In addition, 41 sera were examined for Anti-Cardiolipin (aCL) by a commercial ELISA procedure with 87.8% demonstrating IgM, IgM+IgA, or IgM+IgG aCL antibodies. These results showed mostly the IgM aCL antibody alone in the sera samples. In addition, 41 serum samples were examined for aCL, with 37 showing positive for aCL, representing 90.2% positive for the three disease categories examined: CFS, CCFP and GWV. Examination for antiMitochondrial-M2 autoantibody (aM-M2) in 28 patients (CFS (18), CCFP (5), and GWV (5)) was negative for aM-M2.

Inhibition analysis with antigens, CTX, CFS “Acute Phase Lipids”, commercial Cardiolipin (CL) and 1,2-Dipalmitoyl-sn-Glycero-3-[Phospho-L-Serine] (PS) and antibodies, MAb-CTX and aCL from patients’ serum show that the phospholipids in CL and CTX are antigenically indistinguishable with antibodies MAb-CTX and CFS-aCL. Preliminary chemical analyses have shown the lipids to be phospholipids associated with CL of the mitochondria.

We designate this “Acute Phase Lipid” comparable to “Acute Phase Proteins” (C-reactive protein (CRP) and Serum Amyloid A (SAA)) in inflammatory conditions.

(Copyright ) 2008 Wiley-Liss, Inc.

 

Source: Hokama Y, Empey-Campora C, Hara C, Higa N, Siu N, Lau R, Kuribayashi T, Yabusaki K. Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins. J Clin Lab Anal. 2008;22(2):99-105. doi: 10.1002/jcla.20217. https://www.ncbi.nlm.nih.gov/pubmed/18348309

 

Chronic fatigue syndrome and related disorders in UK veterans of the Gulf War 1990-1991: results from a two-phase cohort study

Abstract:

BACKGROUND: The aim was to determine the prevalence of chronic fatigue syndrome (CFS), chronic fatigue and fibromyalgia in UK military personnel after the Gulf War 1990-1991.

METHOD: A two-phase cohort study was used. Three randomly selected subsamples identified from a population-based cross-sectional postal survey of over 10,000 current and ex-service UK military personnel (Gulf veterans were those deployed to the Gulf War 1990-1991; non-Gulf veterans were Bosnia peacekeepers 1992-1997 and those on active duty during the Gulf War 1990-1991 but not deployed) were recruited. Their disability status was assessed using the Short Form 36 physical functioning scale; Gulf veterans who reported physical disability (n=111) were compared with non-Gulf (n=133) veterans who reported similar levels of physical disability. Screening for known medical and psychiatric conditions was conducted to exclude medical explanations for disability and symptomatic distress. Standardised criteria for CFS, chronic fatigue and fibromyalgia were used.

RESULTS: Disabled Gulf veterans were more likely to be overweight, have elevated gamma-glutamyl transferase levels and screen positive for hypertension. There were no other clinically significant differences in clinical markers for medically explainable conditions. Disabled Gulf veterans were more likely than similarly disabled Bosnia and Era veterans (adjusted odds ratio 7.8, 95% confidence interval 2.5-24.5) to meet the criteria for CFS. Rates for other medically unexplained conditions were not significantly increased.

CONCLUSIONS: Symptoms in keeping with CFS account for a significant part of the symptomatic distress in Gulf veterans.

Comment in: Chronic fatigue in Gulf War veterans: should it be treated as chronic fatigue syndrome? [Psychol Med. 2009]

 

Source: Ismail K, Kent K, Sherwood R, Hull L, Seed P, David AS, Wessely S. Chronic fatigue syndrome and related disorders in UK veterans of the Gulf War 1990-1991: results from a two-phase cohort study. Psychol Med. 2008 Jul;38(7):953-61. Epub 2007 Sep 25. https://www.ncbi.nlm.nih.gov/pubmed/17892626

 

Infection and vaccination in chronic fatigue syndrome: myth or reality?

Abstract:

Chronic fatigue syndrome (CFS) is characterized by severe disabling fatigue lasting for more than 6 months associated with physical and mental disturbances such as headache, arthralgia, myalgia, memory impairment, sore throat and tender lymph nodes. The exact pathogenesis is still unknown. Several models were proposed to explain its etiology including chronic infection, endocrine dysfunction, autonomic imbalance, depression, decreased immunity states and an aberrant reaction to infection. No convincing evidence was found to support any of the suggested pathogenic mechanisms.

The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 dominant response. When the response fails to be switched-off, a chronic immune activation occurs and clinically expressed as the symptomatology of CFS. Vaccinations are used in order to stimulate the immune system to induce a persistent immunity against the favorable antigens.

Several syndromes that contain chronic fatigue as one of their symptoms, such as “Gulf war syndrome” and macrophagic myofasciitis were related to vaccinations. Can vaccinations induce the aberrant immune response of CFS? Little is known about this issue. There are some reports on CFS occurring after vaccination, but few prospective and retrospective studies failed to find such an association. A working group of the Canadian Laboratory Center for Disease Control (LCDC) that was founded in order to examine the suspected association between CFS and vaccinations concluded that there is no evidence that relates CFS to vaccination.

Further studies are requested to examine this issue since it is very conceivable that if infection can lead to CFS, vaccination may also lead to it in the same immune-mediated pathogenesis.

 

Source: Appel S, Chapman J, Shoenfeld Y. Infection and vaccination in chronic fatigue syndrome: myth or reality? Autoimmunity. 2007 Feb;40(1):48-53. https://www.ncbi.nlm.nih.gov/pubmed/17364497

 

Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis

Abstract:

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity.

Adenylate cyclase-activating VNs including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) act as hormones, neurotransmitters, neuroregulators, immune modulators and neurotrophic substances. They and their receptors are potentially immunogenic.

VNs are widely distributed in the body particularly in the central and peripheral nervous systems and have been identified in the gut, adrenal gland, blood cells, reproductive system, lung, heart and other tissues. They have a vital role in maintaining cardio-respiratory function, thermoregulation, memory, concentration and executive functions such as emotional responses including social cues and appropriate behaviour. They are co-transmitters for a number of neurotransmitters including acetylcholine and gaseous transmitters, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system against toxic assault as well as being important in the maintenance of homeostasis.

This paper describes a biologically plausible mechanism for the development of certain fatigue-related syndromes based on loss of immunological tolerance to these VNs or their receptors following infection, other events or de novo resulting in significant pathophysiology possibly mediated via CpG fragments and heat shock (stress) proteins. These conditions extend the public health context of autoimmunity and VN dysregulation and have implications for military medicine where radiological, biological and chemical agents may have a role in pathogenesis. Possible treatment and prevention options are considered.

 

Source: Staines DR. Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis. Clin Dev Immunol. 2006 Mar;13(1):25-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270748/ (Full article)

 

A Chronic Fatigue Syndrome – related proteome in human cerebrospinal fluid

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects.

METHODS: Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50 mul/subject) were pooled into one sample per group (cohort 1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200 mul/subject) assessed individually. After trypsin digestion, peptides were analyzed by capillary chromatography, quadrupole-time-of-flight mass spectrometry, peptide sequencing, bioinformatic protein identification, and statistical analysis.

RESULTS: Pooled CFS and PGI samples shared 20 proteins that were not detectable in the pooled control sample (cohort 1 CFS-related proteome). Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins that were shared by CFS individuals and the cohort 1 CFS-related proteome, but were not detected in control samples. Detection of >or=1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance (logistic model). The proteins were alpha-1-macroglobulin, amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment epithelium-derived factor. Overall, 62 of 115 proteins were newly described.

CONCLUSION: This pilot study detected an identical set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohorts of subjects with overlapping CFS, PGI and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanism(s) may be shared.

 

Source: Baraniuk JN, Casado B, Maibach H, Clauw DJ, Pannell LK, Hess S S. A Chronic Fatigue Syndrome – related proteome in human cerebrospinal fluid. BMC Neurol. 2005 Dec 1;5:22. http://www.ncbi.nlm.nih.gov/pubmed/16321154

 

Gulf War veterans’ health: medical evaluation of a U.S. cohort

Abstract:

BACKGROUND: United States military personnel reported various symptoms after deployment to the Persian Gulf during the 1991 Gulf War. However, the symptoms’ long-term prevalence and association with deployment remain controversial.

OBJECTIVE: To assess and compare the prevalence of selected medical conditions in a national cohort of deployed and nondeployed Gulf War veterans who were evaluated by direct medical and teledermatologic examinations.

DESIGN: A cross-sectional prevalence study performed 10 years after the 1991 Gulf War.

SETTING: Veterans were examined at 1 of 16 Veterans Affairs medical centers.

PARTICIPANTS: Deployed (n = 1061) and nondeployed (n = 1128) veterans of the 1991 Gulf War.

MEASUREMENTS: Primary outcome measures included fibromyalgia, the chronic fatigue syndrome, dermatologic conditions, dyspepsia, physical health-related quality of life (Short Form-36 [SF-36]), hypertension, obstructive lung disease, arthralgias, and peripheral neuropathy.

RESULTS: Of 12 conditions, only 4 conditions were more prevalent among deployed than nondeployed veterans: fibromyalgia (deployed, 2.0%; nondeployed, 1.2%; odds ratio, 2.32 [95% CI, 1.02 to 5.27]); the chronic fatigue syndrome (deployed, 1.6%; nondeployed 0.1%; odds ratio, 40.6 [CI, 10.2 to 161]); dermatologic conditions (deployed, 34.6%; nondeployed, 26.8%; odds ratio, 1.38 [CI, 1.06 to 1.80]), and dyspepsia (deployed, 9.1%; nondeployed, 6.0%; odds ratio, 1.87 [CI, 1.16 to 2.99]). The mean physical component summary score of the SF-36 for deployed and nondeployed veterans was 49.3 and 50.8, respectively.

LIMITATIONS: Relatively low participation rates introduce potential participation bias, and deployment-related illnesses that resolved before the research examination could not, by design, be detected.

CONCLUSIONS: Ten years after the Gulf War, the physical health of deployed and nondeployed veterans is similar. However, Gulf War deployment is associated with an increased risk for fibromyalgia, the chronic fatigue syndrome, skin conditions, dyspepsia, and a clinically insignificant decrease in the SF-36 physical component score.

Comment in: Unexplained suffering in the aftermath of war. [Ann Intern Med. 2005]

 

Source: Eisen SA, Kang HK, Murphy FM, Blanchard MS, Reda DJ, Henderson WG, Toomey R, Jackson LW, Alpern R, Parks BJ, Klimas N, Hall C, Pak HS, Hunter J,Karlinsky J, Battistone MJ, Lyons MJ; Gulf War Study Participating Investigators. Gulf War veterans’ health: medical evaluation of a U.S. cohort. Ann Intern Med. 2005 Jun 7;142(11):881-90. http://www.ncbi.nlm.nih.gov/pubmed/15941694

 

Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans

Abstract:

Genes associated with muscle metabolism and physical endurance were evaluated for variants that may contribute to the etiology of medically unexplained severe and chronic fatigue. Subjects included 49 Gulf War veterans and 61 nonveterans with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) and 30 veterans and 45 nonveterans who served as healthy controls. Increased risk for CFS/ICF was associated with alterations of the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene within the Gulf War veteran sample only. The I allele frequency was decreased in affected versus unaffected veterans (0.15 versus 0.48; odds ratio [OR], 5.08; 95% confidence interval [CI], 1.97-13.35; P < 0.0001). Correspondingly, the II genotype was decreased fourfold in affected veterans (0.08 versus 0.35; OR = 5.87; 95% CI: 1.21-28.36; P = 0.02), and the DD genotype was increased twofold (0.78 versus 0.39; OR, 5.4; 95% CI, 1.6-18.4; P = 0.007). Veterans with the DD genotype were eight times more likely to develop CFS/ICF than were those with the II genotype (OR, 8.30; 95% CI, 1.50-56.09; P = 0.009).

 

Source: Vladutiu GD, Natelson BH. Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans. Muscle Nerve. 2004 Jul;30(1):38-43. http://www.ncbi.nlm.nih.gov/pubmed/15221876

 

Cellular and humoral immune abnormalities in Gulf War veterans

Abstract:

We examined 100 symptomatic Gulf War veterans (patients) and 100 controls for immunologic assays. The veterans and controls were compared for the percentage of T cells (CD3); B cells (CD19); helper:suppressor (CD4:CD8) ratio; natural killer (NK) cell activity; mitogenic response to phytohemagglutin (PHA) and pokeweed mitogen (PWM); level of immune complexes; myelin basic protein (MBP) and striated and smooth muscle autoantibodies; and antibodies against Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 (HSV-1), HSV-2, human herpes Type 6 (HHV-6), and Varicella zoster virus (VZV).

The percentage of T cells in patients versus controls was not significantly different, whereas a significantly higher proportion of patients had elevated T cells compared with controls. The percentage of B cells was significantly elevated in the patients versus the controls. The NK cell (NK) activity was significantly decreased in the patients (24.8 +/- 16.5 lytic units) versus the controls (37.3 +/- 26.4 lytic units). The percentage of patients with lower than normal response to PHA and PWM was significantly different from controls. Immune complexes were significantly increased in the patients (53.1 +/- 18.6, mean +/- SD) versus controls (34.6 +/- 14.3). Autoantibody titers directed against MBP and striated or smooth muscle were significantly greater in patients versus controls.

Finally, the patients had significantly greater titers of antibodies to the viruses compared with the controls (p < 0.001). These immune alterations were detected 2-8 years after participation in the Gulf War. The immune alterations are consistent with exposure to different environmental factors. We conclude that Gulf War syndrome is a multifaceted illness with immune function alterations that may be induced by various factors and are probably associated with chronic fatigue syndrome.

 

Source: Vojdani A, Thrasher JD. Cellular and humoral immune abnormalities in Gulf War veterans. Environ Health Perspect. 2004 Jun;112(8):840-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242010/ (Full article)

 

Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness

Abstract:

Abnormal cardiovascular stress responses have been reported in Gulf War veterans with chronic fatigue. However, many of these veterans also suffer from posttraumatic stress disorder (PTSD), which could potentially explain the reported abnormalities. To test this hypothesis, 55 Gulf veterans (GVs) with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) were stratified into groups with (N=16) and without (N=39) comorbid PTSD, and were compared to healthy Gulf veterans (N=47) on cardiovascular responses to a series of stressors.

The CFS/ICF with PTSD group had lower blood pressure responses to speech and arithmetic tasks, and more precipitous declines and slower recoveries in blood pressure after standing up than the controls. Similar trends in the CF/ICF group without PTSD were not significant, however. Both CFS/ICF groups had blunted increases in peripheral vascular resistance during mental tasks. However, only the veterans with comorbid PTSD had diminished cardiac output responses to the mental stressors and excessive vasodilatory responses to standing. Symptoms of posttraumatic stress were significant predictors of hypotensive postural responses, but only in veterans reporting a significant exposure to wartime stress.

We conclude that comorbid PTSD contributes to dysregulation of cardiovascular responses to mental and postural stressors in Gulf veterans with medically unexplained fatiguing illness, and may provide a physiological basis for increased somatic complaints in Gulf veterans with symptoms of posttraumatic stress.

 

Source: Peckerman A, Dahl K, Chemitiganti R, LaManca JJ, Ottenweller JE, Natelson BH. Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness. Auton Neurosci. 2003 Oct 31;108(1-2):63-72. http://www.ncbi.nlm.nih.gov/pubmed/14614966