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

 

Significance of the chronic fatigue syndrome in rehabilitation medicine–status and perspectives

Abstract:

It appears that from a clinical point of view chronic exhaustion or fatigue is an important factor in rehabilitation. This is, however, first of all a phenomenon that can be described as a function in accordance with the International Classification of Functioning, Disability and Health (JCF), caused by chronic illnesses or chronic excessive stress. The clinical and sociomedical ranking of chronic fatigue or exhaustion in respect of rehabilitation was discussed in the framework of a Workshop at the 12th Rehabilitation Science Colloquium, 2003 from the viewpoints of psychiatric rehabilitation, methodology, sociology and practical rehabilitation, and conclusions for future research were drawn. The definition of chronic fatigue is first of all mainly based on the feeling of chronic tiredness but also on phenomena of disturbed concentration, physical discomfort, headache and disorders of “drive” and mood.

A psychiatric diagnosis linked with symptoms of chronic fatigue is neurasthenia, which is arrived at according to precisely defined criteria. Depressive disorder is one of the most important differential diagnoses in this sphere. Examinations by general practitioners revealed that about 90 % of the patients who had been diagnosed as suffering from psychovegetative disorders completely agreed with the diagnosis of neurasthenia. Neurasthenia resulted more often in work disability periods than disorders of somatisation and other psychosomatic diagnoses. Basing on the “IRES” scale “vital exhaustion”, singular of even serious changes become evident in about 50 % to 90 % of the patients undergoing rehabilitation, depending on their individual range of indications. As was to be expected, the majority of pathologic findings concerns patients undergoing psychosomatic rehabilitation, since in such cases there is an overlapping with symptoms of psychosomatic diseases.

It is, however, remarkable that also in somatically oriented orthopaedic rehabilitation symptoms of fatigue are seen in up to 50 % of the patients. Preliminary studies have shown that these symptoms can be definitely ameliorated within the rehabilitation framework, although pathological signs are still abundantly apparent in follow-up examinations. Markedly severe degrees of “vital exhaustion” and “vocational exhaustion” are also seen in rheumatology patients undergoing somatic rehabilitation. This agrees with case history details related by many female and male patients.

Hence, it appears necessary to adapt rehabilitative intervention to both the psychovegetative and the medical behavioural aspects of this symptom. Scientific classification of the entire sphere of chronic fatigue in respect of rehabilitation requires classification of the relevant functions within the ICF framework. To this end it would be necessary to conduct patient inquiries within cross-sectional studies on the one hand and, on the other, a systematic consensus process among experts would have to be used for allocation to the relevant functions. This is the basis for development of suitable assessment tools for use in prospective studies in order to systematically evaluate the impact on functions and especially their effects on activities and participation.

 

Source: Gutenbrunner C, Linden M, Gerdes N, Ehlebracht-König I, Grosch E. [Significance of the chronic fatigue syndrome in rehabilitation medicine–status and perspectives]. Rehabilitation (Stuttg). 2005 Jun;44(3):176-85. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/15933954

 

Clinical characteristics of patients with chronic fatigue syndrome: analysis of 82 cases

Abstract:

OBJECTIVE: To analyze the clinical characteristics of Chinese patients suffering from chronic fatigue syndrome (CFS) and provide clinical and laboratory evidence for the study of its etiology and treatment.

METHODS: 82 patients with CFS diagnosed based on the CDC criteria 1994 were recruited. History was collected, and physical examination was made. SCL-90 and memory test were used, and Hamilton Anxiety Rating Scale was used to those showing depression and/or anxiety. Laboratory examination, including examination of electrolytes, blood sugar, creatinine, bilirubin, alkaline phosphatase, alanine trasaminase, etc, was conducted. Western blotting was used to detect the protein-24 of Borna disease virus (BDV) in the plasma of 61 patients and 73 healthy controls. High-pressure chromatography was conducted to detect n-6 fatty acids on the membrane of erythrocytes of 42 patients and 37 healthy controls. Plasma L-carnitine in 61 patients and 73 healthy controls was detected by zymological analysis. In different examinations sex and age-matched controls were used.

RESULTS: Most of the patients were 21 approximately 50 years old (74/82, 90.24%). No gender difference was found. The patients usually had 4 approximately 6 symptoms besides distinctive fatigue. Descent of remembrance and/or attention was the most conspicuous accompanying symptoms (69/82, 84.15%). Abnormalities in SCL-90 scores were present in 57 patients (69.51%), e.g, somatization existed most commonly (32/82, 39.02%), and anxiety and depression were 20.73% (17/82) and 18.29% (15/82) respectively. The prevalence of anti-BDV-p24 antibody was 20.73% (17/82), significantly higher than that of the controls (0%, chi(2) = 6.673, P = 0.010). The arachidonic acid level was significantly lower in the CFS group than in the controls (P > 0.05) and there were no differences in linoleic acid and ETA (both P > 0.05). The level of L-carnitine was 6.4336 +/- 3.4225, significantly lower than that of the control group (7.6666 +/- 3.5819, t = 2.025, P = 0.045) and the L-carnitine level was increased 2 weeks after supplementary treatment, together with improvement of symptoms.

CONCLUSION: Most of the CFS patients are young and middle-aged. Descent of reorganization is common in these patients. Psychological abnormalities exist in most patients. Some patients are infected with BDV, some with deficiency of nutrition and/or abnormality of energy metabolism.

 

Source: Li YJ, Wang DX, Bai XL, Chen J, Liu ZD, Feng ZJ, Zhao YM. Clinical characteristics of patients with chronic fatigue syndrome: analysis of 82 cases. Zhonghua Yi Xue Za Zhi. 2005 Mar 16;85(10):701-4. [Article in Chinese] http://www.ncbi.nlm.nih.gov/pubmed/15932738

 

Chronic fatigue syndrome: the need for subtypes

Abstract:

Chronic fatigue syndrome (CFS) is an important condition confronting patients, clinicians, and researchers. This article provides information concerning the need for appropriate diagnosis of CFS subtypes. We first review findings suggesting that CFS is best conceptualized as a separate diagnostic entity rather than as part of a unitary model of functional somatic distress. Next, research involving the case definitions of CFS is reviewed.

Findings suggest that whether a broad or more conservative case definition is employed, and whether clinic or community samples are recruited, these decisions will have a major influence in the types of patients selected. Review of further findings suggests that subtyping individuals with CFS on sociodemographic, functional disability, viral, immune, neuroendocrine, neurology, autonomic, and genetic biomarkers can provide clarification for researchers and clinicians who encounter CFS’ characteristically confusing heterogeneous symptom profiles.

Treatment studies that incorporate subtypes might be particularly helpful in better understanding the pathophysiology of CFS. This review suggests that there is a need for greater diagnostic clarity, and this might be accomplished by subgroups that integrate multiple variables including those in cognitive, emotional, and biological domains.

 

Source: Jason LA, Corradi K, Torres-Harding S, Taylor RR, King C. Chronic fatigue syndrome: the need for subtypes. Neuropsychol Rev. 2005 Mar;15(1):29-58. http://www.ncbi.nlm.nih.gov/pubmed/15929497

 

Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome

Abstract:

BACKGROUND: The aim of the present study was to obtain a naturalistic measure of diurnal hypothalamic-pituitary-adrenal (HPA) axis output in CFS patients unaffected by medication or comorbid psychiatric disorder likely to influence the axis.

METHOD: Cortisol and cortisone levels were measured in saliva samples collected from 0600 h to 2100 h at 3-h intervals in CFS patients and healthy controls.

RESULTS: Mean cortisol and cortisone concentrations were significantly lower in patients than controls across the whole day, as were levels at each individual time point except 2100 h. Cosinor analysis showed a significant diurnal rhythm of cortisol and cortisone that was not phase-shifted in CFS compared to controls. However, there was a lower rhythm-adjusted mean and a lower amplitude in CFS patients. The cortisol/cortisone ratio showed no diurnal rhythm and did not differ between CFS subjects and controls.

LIMITATIONS: The sample size was relatively small, and drawn from specialist referral patients who had been ill for some time; generalisation of these results to other populations is therefore unwarranted.

CONCLUSION: The main findings of this study are to provide further evidence for reduced basal HPA axis function in at least some patients with CFS and to show for the first time that salivary cortisone is also reduced in CFS and has a diurnal rhythm similar to that of cortisol. We have also demonstrated that the cortisol/cortisone ratio remains unchanged in CFS, suggesting that increased conversion of cortisol to cortisone cannot account for the observed lowering of salivary cortisol.

 

Source: Jerjes WK, Cleare AJ, Wessely S, Wood PJ, Taylor NF. Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome. J Affect Disord. 2005 Aug;87(2-3):299-304. http://www.ncbi.nlm.nih.gov/pubmed/15922454

 

Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome

Abstract:

People with chronic fatigue syndrome (CFS) suffer from multiple symptoms including fatigue, impaired memory and concentration, unrefreshing sleep and musculoskeletal pain. The exact causes of CFS are not known, but the symptom complex resembles that of several diseases that affect the immune system and autoantibodies may provide clues to the various etiologies of CFS.

We used ELISA, immunoblot and commercially available assays to test serum from subjects enrolled in a physician-based surveillance study conducted in Atlanta, Georgia and a population-based study in Wichita, Kansas for a number of common autoantibodies and antibodies to neuron specific antigens.

Subsets of those with CFS had higher rates of antibodies to microtubule-associated protein 2 (MAP2) (p = 0.03) and ssDNA (p = 0.04). There was no evidence of higher rates for several common nuclear and cellular antigens in people with CFS. Autoantibodies to specific host cell antigens may be a useful approach for identifying subsets of people with CFS, identify biomarkers, and provide clues to CFS etiologies.

 

Source: Vernon SD, Reeves WC.  Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome. J Autoimmune Dis. 2005 May 25;2:5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1177983/ (Full article)

 

Salivary cortisol as a predictor of postoperative fatigue

 Abstract:

OBJECTIVE: Some patients with chronic fatigue syndrome (CFS) exhibit low basal cortisol levels, but it is not known whether low cortisol is a cause of CFS, predates the onset of CFS symptoms, or is an epiphenomenon caused by the behavioral changes typical of CFS. Because elective surgery is one of the few predictable risk factors for chronic fatigue, in this study, we followed a cohort of surgery patients from before to 6 months after their operation to test these theories.

METHOD: One hundred sixty-one patients completed fatigue questionnaires and provided salivary cortisol samples before undergoing an elective inpatient surgical procedure, and then 2 days, 3 weeks, and 6 months afterward.

RESULTS: Controlling for relevant demographic and surgical variables and for preoperative fatigue, low preoperative cortisol did not predict postoperative fatigue severity on any occasion (p > .05). Similarly, there was no correlation between low postoperative cortisol and postoperative fatigue severity at 3 weeks or 6 months (p > .05). Although 16 patients met our case definition for “chronic fatigue” at the 6-month follow up, low preoperative and low postoperative cortisol did not significantly predict fatigue caseness (p > .05).

CONCLUSIONS: Any association between chronic fatigue and low cortisol would seem to develop after the onset of fatigue symptoms. Low cortisol is therefore unlikely to be the primary cause of chronic fatigue states.

 

Source: Rubin GJ, Hotopf M, Papadopoulos A, Cleare A. Salivary cortisol as a predictor of postoperative fatigue. Psychosom Med. 2005 May-Jun;67(3):441-7. http://www.ncbi.nlm.nih.gov/pubmed/15911908 

 

24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome

Abstract:

OBJECTIVES: Disturbances of neuroendocrine function, particularly the hypothalamo-pituitary-adrenal (HPA) axis, have been implicated in the pathophysiology of chronic fatigue syndrome (CFS). However, few studies have attempted to measure blood levels of pituitary or adrenal hormones across a whole 24-hour period in CFS, and those that did so have used infrequent sampling periods. Our aim was to assess 24-hour pituitary and adrenal function using frequent blood sampling.

METHODS: We recruited 15 medication-free patients with CFS without comorbid psychiatric disorder and 10 healthy control subjects. Blood samples were collected over 24 hours and assayed for cortisol, corticotropin (ACTH), growth hormone (GH), and prolactin (PRL) levels on an hourly basis during daytime hours (10 am to 10 pm) and every 15 minutes thereafter (10 pm to 10 am).

RESULTS: Repeated-measures analyses of variance were undertaken using hormone levels averaged over 2-hour blocks to smooth curves by reducing the influence of sample timing relative to secretory burst. For ACTH, there was both a main effect of group, suggesting reduced mean ACTH secretion in patients with CFS over the whole monitoring period, and a group-by-time interaction, suggesting a differential pattern of ACTH release. Post hoc analysis showed reduced ACTH levels in CFS during the 8 am to 10 am period. In contrast, there were no significant abnormalities in the levels of cortisol, GH, and PRL in patients with CFS over the full cycle compared with control subjects. Cosinor analysis found no differences in the cortisol circadian rhythm parameters, but the ACTH rhythm did differ, patients with CFS showing an earlier acrophase.

CONCLUSIONS: Patients with CFS demonstrated subtle alterations in HPA axis activity characterized by reduced ACTH over a full circadian cycle and reduced levels during the usual morning physiological peak ACTH secretion. This provides further evidence of subtle dysregulation of the HPA axis in CFS. Whether this dysregulation is a primary feature of the illness or instead represents a biologic effect secondary to having the illness itself remains unclear.

 

Source: Di Giorgio A, Hudson M, Jerjes W, Cleare AJ. 24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome. Psychosom Med. 2005 May-Jun;67(3):433-40. http://www.ncbi.nlm.nih.gov/pubmed/15911907

 

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory

Abstract:

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT).

We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for.

Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99).

Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

 

Source: Lange G, Steffener J, Cook DB, Bly BM, Christodoulou C, Liu WC, Deluca J, Natelson BH. Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory. Neuroimage. 2005 Jun;26(2):513-24. Epub 2005 Apr 7. http://www.ncbi.nlm.nih.gov/pubmed/15907308

 

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution

Abstract:

BACKGROUND: A recent article by Reeves et al. on the identification and resolution of ambiguities in the 1994 chronic fatigue syndrome (CFS) research case definition recommended the Checklist Individual Strength, the Chalder Fatigue Scale, and the Krupp Fatigue Severity Scale for evaluating fatigue in CFS studies. To be able to discriminate between various levels of severe fatigue, extreme scoring on the individual items of these questionnaires must not occur too often.

METHODS: We derived an expression that allows us to compute a lower bound for the number of items with the maximum item score for a given study from the reported mean scale score, the number of reported subjects, and the properties of the fatigue rating scale. Several CFS studies that used the recommended fatigue rating scales were selected from literature and analyzed to verify whether abundant extreme scoring had occurred.

RESULTS: Extreme scoring occurred on a large number of the items for all three recommended fatigue rating scales across several studies. The percentage of items with the maximum score exceeded 40% in several cases. The amount of extreme scoring for a certain scale varied from one study to another, which suggests heterogeneity in the selected subjects across studies.

CONCLUSION: Because all three instruments easily reach the extreme ends of their scales on a large number of the individual items, they do not accurately represent the severe fatigue that is characteristic for CFS. This should lead to serious questions about the validity and suitability of the Checklist Individual Strength, the Chalder Fatigue Scale, and the Krupp Fatigue Severity Scale for evaluating fatigue in CFS research.

Comment on: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. [BMC Health Serv Res. 2003]

 

Source: Stouten B. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2005 May 13;5:37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175848/ (Full article)