ABSTRACT: BACKGROUND: The pathophysiology of chronic fatigue syndrome (CFS) in adolescents is unknown, and the clinical course and prognosis is still questioned. Recent research indicates that abnormalities of autonomic cardiovascular control may play an important role. The aim of this research project was to perform a follow-up study of adolescents with chronic fatigue syndrome, focusing on clinical symptoms and autonomic cardiovascular control. METHODS: 47 adolescents (12-18 years old) with CFS were recruited from the outpatient clinic at the Department of Pediatrics, Oslo University Hospital. In a primary visit and a follow-up visit (3-17 months later), we evaluated: a) a wide range of complaints and symptoms and b) cardiovascular variables at baseline and during a 20o head-up tilt-test (HUT). RESULTS: At the second visit, patients reported significant improvement regarding functional impairments, fatigue severity, muscular pain, concentration problems, post-exertional malaise and the problem of non-relieving rest. Also, at the second visit, baseline heart rate (HR), blood pressure, total peripheral resistance index (TPRI) and LF/HF (low-frequency:high-frequency heart rate variability ratio, an index of sinus node sympathovagal balance derived from spectral analyses of heart rate) were significant lower, and the increases in HR, mean blood pressure (MBP), diastolic blood pressure (DBP) and TPRI during tilt were significantly less pronounced as compared to the first visit. There was a significant correlation between changes in autonomic symptom score, fatigue severity score and functional impairment score from the first to the second visit. CONCLUSIONS: The majority of adolescents with CFS experienced an improvement over time in functional impairment, self-reported fatigue and additional symptoms, and a concurrent improvement of autonomic cardiovascular control. A possible connection between clinical symptoms and abnormal autonomic control in CFS might represent a focus for further research.

Purpose. The aim of this pilot study was to explore illness beliefs and coping strategies among adolescent patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), applying a qualitative methodology. Recent studies have explored the illness beliefs and coping strategies of adult patients with CFS/ME as possible contributing factors to the disease aetiology. These studies have mainly used quantitative methods, finding that patients often explain their illness as being due to physical causes, deny psychological causes and make use of passive and avoidant coping strategies. Method. Semi-structured, in-depth interviews were conducted with nine adolescent patients with CFS/ME, thematic analysis was adapted to the material and the results were interpreted in light of theories of attribution and coping. Results. The qualitative method allowed for more complex and nuanced accounts of illness experience. The findings showed that the adolescents differ from what has previously been reported, applying more varied and flexible illness attributions and coping mechanisms than expected. Conclusions. The heterogeneity suggested in the results has implications. We suggest three perspectives should be taken into account, both for further research and in clinical practice:(1) individual differences;(2) a developmental perspective and (3) interactive relational focus.

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.