Abstract Aim: The chronic fatigue syndrome is associated with alterations in the hypothalamus-pituitary-adrenal axis and cardiovascular autonomic nervous activity, suggesting a central dysregulation. This study explored differences among adolescent chronic fatigue syndrome patients and healthy controls regarding antidiuretic hormone, the renin-angiotensin-aldosterone-system, sex hormones and cardiac peptides. Methods: We included a consecutive sample of 67 adolescents aged 12-18 years with chronic fatigue syndrome diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 55 healthy control subjects of equal gender and age distribution. Hormones were assayed with standard laboratory methods. Results: Among patients, plasma antidiuretic hormone was significantly decreased and serum osmolality and plasma renin activity were significantly increased (p </= 0.001). Serum concentration of aldosterone, cortisol, NT-proBNP and sex hormones were not significantly different in the two groups. Conclusion: Chronic fatigue syndrome in adolescents is associated with alterations in hormonal systems controlling osmolality and blood volume, possibly supporting a theory of central dysregulation.

Aim: The present study investigates associations between autonomic cardiovascular dysregulation, psychosocial load and mental health in adolescents presenting with chronic fatigue. Method: Twenty-two adolescents, mean age 15.7 years (12.7-19.1), underwent a clinical mental health examination as part of a broad medical investigation which included autonomic tests. Adolescents and their parents were also interviewed with regard to psychosocial stress factors, family health and previous illnesses. A count of psychosocial load was made for each adolescent based on the interview. Results: Of 22 fatigued adolescents in the present sample, 14 had psychiatric diagnoses. There was no significant difference in psychosocial load for the fatigued adolescents classified with normal autonomic regulation compared to those with deviant or borderline autonomic regulation. The present psychiatric diagnosis did not differ between the two groups. In a subsample, there was a significant negative association between depressive symptoms and abnormal blood pressure responses during orthostatic challenge. Conclusion: No significant psychiatric or psychosocial differences between fatigued adolescents with or without autonomic dysregulation were found in this study. The trends towards higher psychosocial load and greater burden of depressive symptoms in fatigued adolescents with normal autonomic regulation warrant further studies.

Arrhythmias in patients with repaired tetralogy of Fallot (ToF) might be due in part to altered autonomic heart rate control caused by altered right ventricle hemodynamics. This study investigated autonomic heart rate control in adolescents with ToF at rest and during unloading of the right ventricle. A total of 17 patients with ToF and 56 healthy controls aged 12 to 18 years underwent orthostatic stress with lower body negative pressure of -20 mm Hg. Heart rate, blood pressure, and stroke volume were recorded noninvasively. Indices of heart rate variability were computed in time and frequency domains. All patients with ToF also underwent cardiac magnetic resonance imaging, demonstrating pulmonary regurgitation and right ventricular dilation. At rest, heart rate variability indices of vagal heart rate control were nonsignificantly lower in the patients with ToF compared with controls. During lower body negative pressure, heart rate increased more in controls than patients with ToF (p </=0.001). Further, most heart rate variability indices decreased in controls, but increased in patients with ToF (p </=0.01 or p </=0.001 for all variables), suggesting vagal activation in the patients with ToF. In conclusion, adolescents after ToF repair have fairly normal heart rate control at rest despite altered right ventricular hemodynamics. During unloading of the right ventricle, however, vagal heart rate control increases in the patients with ToF and decreases in the controls.

Background: Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to investigate autonomic heart rate control during mild orthostatic stress in adolescents with CFS. Methods: A total of 14 CFS patients and 56 healthy controls having equal distribution of age and gender underwent lower body negative pressure (LBNP) of horizontal line 20 mmHg. The RR interval (RRI) was recorded continuously, and spectral power densities were computed in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.50 Hz) from segments of 120-second length, using an autoregressive algorithm. In addition, the time-domain indices SDNN, pNN50, and r-MSSD were computed. Results: At rest, CFS had lower RRI than controls (P < 0.05), but indices of variability were similar in the two groups. During LBNP, compared to controls, CFS patients had lower normalized and absolute HF power and r-MSSD (P < 0.05), and higher RRI (P < 0.001), normalized LF power and LF/HF (P < 0.05). Conclusions: During mild orthostatic stress, adolescents with CFS appear to have enhanced vagal withdrawal, leading to a sympathetic predominance of heart rate control compared to controls. Possible underlying mechanisms include hypovolemia and abnormalities of reflex mechanisms.

OBJECTIVES. Chronic fatigue syndrome is a common and disabling disease of unknown etiology. Accumulating evidence indicates dysfunction of the autonomic nervous system. To further explore the pathophysiology of chronic fatigue syndrome, we investigated thermoregulatory responses dependent on catecholaminergic effector systems in adolescent patients with chronic fatigue syndrome. PATIENTS AND METHODS. A consecutive sample of 15 patients with chronic fatigue syndrome aged 12 to 18 years and a volunteer sample of 57 healthy control subjects of equal gender and age distribution were included. Plasma catecholamines and metanephrines were measured before and after strong cooling of 1 hand. Acral skin blood flow, tympanic temperature, heart rate, and mean blood pressure were measured during moderate cooling of 1 hand. In addition, clinical symptoms indicative of thermoregulatory disturbances were recorded. RESULTS. Patients with chronic fatigue syndrome reported significantly more shivering, sweating, sudden change of skin color, and feeling unusually warm. At baseline, patients with chronic fatigue syndrome had higher levels of norepinephrine, heart rate, epinephrine, and tympanic temperature than control subjects. During cooling of 1 hand, acral skin blood flow was less reduced, vasoconstrictor events occurred at lower temperatures, and tympanic temperature decreased more in patients with chronic fatigue syndrome compared with control subjects. Catecholamines increased and metanephrines decreased similarly in the 2 groups. CONCLUSIONS. Adolescent patients with chronic fatigue syndrome have abnormal catecholaminergic-dependent thermoregulatory responses both at rest and during local skin cooling, supporting a hypothesis of sympathetic dysfunction and possibly explaining important clinical symptoms.

Haemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular control. This study was designed to explore the pathophysiology in adolescent CFS-patients by analysing RR-interval (RRI) variability and diastolic blood pressure (DBP) variability during mild orthostatic stress, using an algorithm which accounts for non-stationary biosignals. A total of 27 adolescents with CFS and 33 healthy control subjects having equal age- and sex distribution underwent 15 min of 20 degrees head-up tilt (HUT). The spectral power densities of RRI and DBP were computed in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.4 Hz) using an adaptive autoregressive algorithm to obtain a time-varying spectrum. RMSSD, a time domain index of RRI variability, was also computed. At rest, all indices of variability were similar in the two groups. During tilt, CFS patients had a larger increase in the LF/HF ratio (P</=0.001) and normalized LF power of RRI (P</=0.01), and a larger decrease in normalized HF power (P</=0.01) of RRI than controls. CFS patients also had trends towards a larger decrease in absolute HF power of RRI and a larger increase in normalized LF power of DBP. These findings suggest that adolescents with CFS have sympathetic predominance of cardiovascular regulation during very mild orthostatic stress. Possible underlying mechanisms are moderate hypovolemia, abnormalities of reflex control or physical de-conditioning.

We describe the effect of propranolol in an adolescent with chronic fatigue syndrome and orthostatic intolerance. Our observations suggest that the head-up tilt-test and beta-blocker treatment might be considered in patients with chronic fatigue syndrome and that enhanced sympathetic nervous activity might be part of the underlying pathophysiology.

Background - In this article, current scientific knowledge on the chronic fatigue syndrome (CFS) is reviewed. The US case definition of CFS (the CDC-definition) is most widespread in research and clinical practice. Estimates of prevalence vary from 0.2% to above 2%. The female-male ratio is approximately 3:1. Clinical Features - Severe fatigue is the dominating complaint; it is worsened from exertions and not substantially relieved by rest. In addition, the patients might have a varying combination of accompanying symptoms. Clinical evaluation should be based upon standardized guidelines, including an assessment of functional impairments. Pathophysiology - The pathophysiology should be interpreted within a biopsychosocial framework. Present knowledge suggests that certain genetic polymorphisms and personality traits might be regarded as predisposing factors, some infections and severe psychosocial stress constitute precipitating factors, whereas disturbances of immunity, skeletal muscle, cognitive abilities, endocrine control and cardiovascular homeostasis are possible perpetuating factors. Treatment - Cognitive behavioural therapy and graded exercise therapy are of proven value in randomized controlled trials. Several pharmaceutical measures have been explored and found to have no beneficial effect. Most patients might expect long-term improvement, but full recovery is rare; however, the prognosis is better among adolescents.

Hemodynamic dysfunction is documented in chronic fatigue syndrome (CFS). This study was conducted to investigate cardiovascular responses to orthostatic stress in adolescents with CFS, using a novel procedure for tilt-table testing. A total of 27 adolescents with CFS and 33 healthy control subjects with equal age and gender distribution underwent 15 minutes of 20 degrees head-up tilt testing. Heart rate, systolic blood pressure (BP), mean BP, diastolic BP, stroke index, total peripheral resistance index, end-diastolic volume index, and acceleration index were continuously and noninvasively recorded. At rest, patients with CFS had higher total peripheral resistance index values (p<0.01) and lower stroke index and end-diastolic volume index values (p<0.05) than controls. During 20 degrees head-up tilt testing, patients with CFS had greater increases in heart rate, diastolic BP (p<0.001), mean BP (p<0.01), and total peripheral resistance index (p<0.05) than controls and greater decreases in stroke index (p<0.05). Syncope or near syncope was not observed. In conclusion, this study found that adolescents with CFS have significant abnormalities of cardiovascular regulation in response to mild orthostatic stress, differentiating them from healthy controls.