P.M.M.B. Soetekouw

Autonomic function in patients with chronic fatigue syndrome

Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in 37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be lower in CFS patients (28.4±10.5 beats) than in healthy controls (32.2±9.5) (p=0.11). The maximal increase in HR during standing up was not significantly different between the CFS group (37.6±8.9 beats) and the control group (40.2±8.9 beats). There were no significant differences between both groups with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva maneuver. The HR response to MA was significantly less in the CFS group (22.6±9.9) than in the control group (29.5±16.7) (p<0.05), suggesting impaired cardiac sympathetic responsiveness to mental stress. The lower HR responses could not be explained by the level of concentration in the CFS group. During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group, but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant differences between CFS patients with and without symptoms of autonomic dysfunction regarding the hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are no gross alterations in cardiovascular autonomic function in patients with CFS.

Hemodynamic and neurohumoral responses to head-up tilt in patients with chronic fatigue syndrome.

Abstract.Background: Data on the prevalence of orthostatic intolerance (OI) in patients with chronic fatigue syndrome (CFS) are limited and controversial. We tested the hypothesis that a majority of CFS patients exhibit OI during head-up tilt. Methods: Hemodynamic and neurohumoral responses to 40 minutes of head-up tilt were studied in 36 CFS patients and 36 healthy controls. Changes in stroke volume, cardiac output and peripheral vascular resistance were estimated from finger arterial pressure waveform analysis (Modelflow). Blood samples were drawn before and at the end of head-up tilt for measurement of plasma catecholamines. Results: At baseline, supine heart rate was higher in CFS patients (CFS: 66.4 ± 8.4 bpm; controls: 57.4 ± 6.6 bpm; p < 0.001) as was the plasma epinephrine level (CFS: 0.11 ± 0.07 nmol/l; controls: 0.08 ± 0.07 nmol/l: p = 0.015). An abnormal blood pressure and/or heart rate response to head-up tilt was seen in 10 (27.8 %) CFS patients (6 presyncope, 2 postural tachycardia, 2 tachycardia and presyncope) and 6 (16.7 %, p = 0.26) controls (5 presyncope, 1 tachycardia, 2 tachycardia and presyncope). Head-up tilt-negative CFS patients showed a larger decrease in stroke volume during tilt (−46.9 ± 10.6) than head-up tilt-negative controls (−40.3 ± 13.6 %, p = 0.008). Plasma catecholamine responses to head-up tilt did not differ between these groups. Conclusion: Head-up tilt evokes postural tachycardia or (pre)syncope in a minority of CFS patients. The observations in head-up tilt-negative CFS patients of a higher heart rate at baseline together with a marked decrease in stroke volume in response to head-up tilt may point to deconditioning.

Somatic hypotheses of war syndromes

Since the end of the American Civil War, unexplained symptoms in military personnel arising after a war or peace mission have frequently been described. The pattern of symptoms is highly similar for all of the various war syndromes although the conditions of each war or peace mission are widely different. Many somatic hypotheses have been formulated to explain these syndromes; a considerable proportion of them are already outdated. In the last few years much attention has been given to Gulf War Syndrome and to unexplained symptoms of military personnel who were sent to Cambodia, Rwanda, Burundi, Zaire, or the former Yugoslavia. In this review the symptoms of war syndromes will be considered in more detail and the suggested somatic explanations will be discussed. During the last decade the following somatic causes have been suggested as possible explanations for these symptoms: (persistent) infection, abnormal immune response, administration of multiple vaccinations within a short period of time, use of malaria chemoprophylaxis, neurological abnormalities, exposure to toxicological substances and environmental factors. The various investigations performed to study these hypotheses are discussed. The fact that bias regularly occurs in the course of these investigations is pointed out. For the future, a reliable investigation of a war syndrome should be a prospective multidisciplinary study and should distinguish between causative and sustaining factors.

Normal carnitine levels in patients with chronic fatigue syndrome.

BACKGROUND Patients with chronic fatigue syndrome (CFS) complain of muscle pain and impaired exercise tolerance. Previous studies show that this is due to systemic carnitine deficiency. We investigated the hypothesis that carnitine deficiency plays an important role in CFS in female CFS patients and compared their results with neighbourhood controls. METHODS The level of total carnitine, free carnitine, acylcarnitine and carnitine esters were measured in 25 female CFS patients and 25 healthy matched neighbourhood controls in a blinded fashion. RESULTS The previously reported decreased level of acylcarnitine in CFS patients was not confirmed. There were also no significant differences in levels of total carnitine, free carnitine and 20 carnitine esters between CFS patients and controls. CONCLUSIONS The present study demonstrates that serum carnitine deficiency does not contribute to or causes the symptoms in many CFS patients.

Persistent symptoms in former UNTAC soldiers are not associated with shifted cytokine balance.

The pathogenesis of post‐combat syndromes, such as Gulf War syndrome, is poorly understood. Recently, it has been postulated that the symptoms of veterans with such syndromes are due to a disturbed cytokine balance shifted towards a T‐helper (Th) 2 profile. We investigated this hypothesis in 21 symptomatic former UNTAC soldiers and compared their results with those obtained in 21 healthy former UNTAC soldiers matched for age, sex and military force.

Natural course of symptoms in Cambodia veterans: a follow-up study

BACKGROUND Dutch (ex-)servicemen were deployed in the 1992-3-peace operation UNTAC in Cambodia. Since their return, they have voiced concerns about the health consequences of their service and they have reported symptoms such as fatigue and cognitive problems. The natural course of symptoms in Dutch Cambodia veterans was evaluated in a prospective study. METHODS At 18-months follow-up, a questionnaire was sent to 354 veterans who met a set case definition for symptoms in Cambodia veterans or who had sub-threshold scores. Initial measurement of fatigue severity, psychological well-being, depression, post-traumatic stress disorder, trait-anxiety, self-efficacy and causal attributions, was used to evaluate predictors for self-reported improvement and low levels of fatigue at follow-up. RESULTS At follow-up, 19% of the respondents reported complete recovery, 20% felt much better, 57% had the same complaints and 4% had become worse compared with their initial assessment. Self-reported improvement and less severe fatigue at follow-up were predicted by less severe fatigue at initial assessment and more perceived control over symptoms. CONCLUSIONS Self-reported improvement was reported in a considerable percentage of Cambodia veterans, whereas another substantial percentage of Cambodia veterans continued to suffer with severe levels of fatigue and related symptoms. Predictors of improvement in Cambodia veterans and patients with chronic fatigue syndrome show similarities and also seem to bear importance for Gulf War veterans.