Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) has been shown to be associated with orthostatic intolerance and cardiovascular dysregulation. We investigated the cardiovascular responses to combined orthostatic stress and isometric exercise in adolescents with CFS.

We included a consecutive sample of 15 adolescents 12-18 years old with CFS diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 56 healthy control subjects of equal sex and age distribution. Heart rate, systolic, mean and diastolic blood pressure, stroke index, and total peripheral resistance index were non-invasively recorded during lower body negative pressure (LBNP) combined with two consecutive periods of handgrip. In addition, we measured baseline plasma catecholamines, and recorded symptoms. At rest, CFS patients had higher heart rate, diastolic blood pressure, plasma norepinephrine (P < 0.01), mean blood pressure and plasma epinephrine (P < 0.05) than controls.

During LBNP, CFS patients had a greater increase in heart rate, diastolic blood pressure, mean blood pressure (P < 0.05) and total peripheral resistance index (n.s.) than controls. During handgrip, CFS patients had a smaller increase in heart rate, diastolic blood pressure (P < 0.05), mean blood pressure and total peripheral resistance index (n.s.) than controls.

Our results indicate that adolescents with CFS have increased sympathetic activity at rest with exaggerated cardiovascular response to orthostatic stress, but attenuated cardiovascular response when performing isometric exercise during orthostatic stress. This suggests that CFS might be causally related to sympathetic dysfunction.

 

Source: Wyller VB, Saul JP, Walløe L, Thaulow E. Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. Eur J Appl Physiol. 2008 Apr;102(6):623-32. Epub 2007 Dec 8. https://www.ncbi.nlm.nih.gov/pubmed/18066580

 

Successful use of a primary care practice-specialty collaboration in the care of an adolescent with chronic fatigue syndrome

Abstract:

We report on the successful collaborative care of an adolescent with chronic fatigue syndrome between a primary care pediatrician and an academic chronic fatigue syndrome specialist located in different cities. Regular telephone and e-mail communication and clearly defined patient-care roles allowed for timely management of symptoms and marked clinical improvement. We discuss ways to improve the collaboration of primary care and subspecialty physicians for patients with chronic fatigue syndrome and children with special health care needs.

 

Source: Kuo DZ, Cheng TL, Rowe PC. Successful use of a primary care practice-specialty collaboration in the care of an adolescent with chronic fatigue syndrome. Pediatrics. 2007 Dec;120(6):e1536-9. https://www.ncbi.nlm.nih.gov/pubmed/18055669

 

Actigraphic assessment of sleep disorders in children with chronic fatigue syndrome

Abstract:

Children with chronic fatigue syndrome (CFS) often suffer from sleep disorders, which cause many physiological and psychological problems. Understanding sleep characteristics in children with CFS is important for establishing a therapeutic strategy. We conducted an actigraphic study to clarify the problems in sleep/wake rhythm and physical activity in children with CFS.

METHODS: Actigraphic recordings were performed for 1-2 weeks in 12 CFS children. The obtained data were compared with those of healthy age-matched children used as the control.

RESULTS: Sleep patterns were divided into two groups based on subjects’ sleep logs: irregular sleep type and delayed sleep phase type. Compared to the control group, total sleep time was longer and physical activity was lower in both groups of CFS. Continuous sleep for more than 10h was not uncommon in CFS. In the irregular sleep type, impaired daily sleep/wake rhythms and disrupted sleep were observed.

CONCLUSION: Using actigraphy, we could identify several characteristics of the sleep patterns in CFS children. Actigraphic analysis proved to be useful in detecting sleep/wake problems in children with CFS.

 

Source: Ohinata J, Suzuki N, Araki A, Takahashi S, Fujieda K, Tanaka H. Actigraphic assessment of sleep disorders in children with chronic fatigue syndrome. Brain Dev. 2008 May;30(5):329-33. Epub 2007 Nov 26. https://www.ncbi.nlm.nih.gov/pubmed/18031961

 

Alexithymia in adolescents with chronic fatigue syndrome

Abstract:

BACKGROUND: Alexithymia is postulated as an important factor in the development of medically unexplained physical symptoms. Chronic fatigue syndrome (CFS) is presently medically unexplained. The aim of this study was to investigate whether the prevalence of alexithymia was higher in adolescents with CFS compared to healthy adolescents. Comorbidity such as anxiety and depression were analyzed as possible confounding factors. Secondly, alexithymia was investigated as a prognostic factor for the recovery of CFS.

METHODS: A cross-sectional study was performed among 40 adolescent outpatients diagnosed with CFS and 36 healthy controls. The 20-item Toronto Alexithymia Scale was used to assess all participants for alexithymia. Additionally, all participants completed a number of questionnaires regarding fatigue (Checklist Individual Strength), somatic complaints (Checklist Somatization Inventory), depression (Children’s Depression Inventory), and trait anxiety (Spielberger State Trait Anxiety Questionnaire). A follow-up study was performed among the CFS adolescents 1 1/2 years after the initial assessment.

RESULTS: CFS adolescents scored higher only on the subscale identifying feelings of the TAS-20 [mean difference after adjustment for depression and anxiety 2.8 (95% CI: 0.6; 4.9]. Twelve CFS adolescents (30%) fulfilled criteria for alexithymia. This subgroup was characterized by higher scores for depression and anxiety and equal scores for fatigue and somatic complaints. At follow-up, no differences in recovery were established between the alexithymic and nonalexithymic CFS adolescents.

CONCLUSIONS: Alexithymia neither appears to be a unique correlate of CFS nor to be a prognostic factor for recovery of the CFS illness.

 

Source: van de Putte EM, Engelbert RH, Kuis W, Kimpen JL, Uiterwaal CS. Alexithymia in adolescents with chronic fatigue syndrome. J Psychosom Res. 2007 Oct;63(4):377-80. https://www.ncbi.nlm.nih.gov/pubmed/17905045

 

Abnormal thermoregulatory responses in adolescents with chronic fatigue syndrome: relation to clinical symptoms

Abstract:

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.

 

Source: Wyller VB, Godang K, Mørkrid L, Saul JP, Thaulow E, Walløe L. Abnormal thermoregulatory responses in adolescents with chronic fatigue syndrome: relation to clinical symptoms. Pediatrics. 2007 Jul;120(1):e129-37. https://www.ncbi.nlm.nih.gov/pubmed/17606539

 

Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue

Abstract:

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<or=0.001) and normalized LF power of RRI (P<or=0.01), and a larger decrease in normalized HF power (P<or=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.

 

Source: Wyller VB, Saul JP, Amlie JP, Thaulow E. Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue. Clin Physiol Funct Imaging. 2007 Jul;27(4):231-8. https://www.ncbi.nlm.nih.gov/pubmed/17564672

 

School phobia and childhood chronic fatigue syndrome (CCFS)

Abstract:

Chronic fatigue occurring in previously healthy children and adolescents is a vexing problem encountered by pediatric practitioners and the impact of fatigue in youngsters should not be underestimated. In its severe form, it is often associated with mood disorders. Findings in children and adolescent cases suggest that severe unexplained fatigue might precede the development of fatigue-related illness, such as childhood chronic fatigue syndrome (CCFS). This is a disabling condition characterized by severe disabling fatigue and a combination of symptoms, the prominent features being self-reported impairments in concentration and short-term memory, sleep disturbances and autonomic symptoms that cannot be explained by medical or psychiatric illness. We have encountered such patients with these complaints; their major symptoms include: general fatigue, fever, headache (not migraine), and memory disturbance. From our clinical experience, we have inferred that patients with CCFS might experience changes in brain function levels, which induce an autonomic imbalance and engender symptoms such as general fatigue, higher-order level cognitive dysfunction, and memory disturbance.

 

Source: Tomoda A. School phobia and childhood chronic fatigue syndrome (CCFS). Nihon Rinsho. 2007 Jun;65(6):1121-33. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561707

 

Autonomic function and child chronic fatigue syndrome

Abstract:

It is postulated that child chronic fatigue syndrome (CFS) involves the autonomic nervous system, although the precise mechanism has not been clearly indicated. This paper reviews recent reports focusing the role of the autonomic nervous system which plays in CFS. Many of the method for measuring autonomic function have appeared in the clinical setting in parallel with advancing computer technology, but these are limited when applied in children. In these blood pressure and heart rate changes during orthostatic stress and these variability are favorably used. As a result, one third of children with CFS showed abnormal cardiovascular adjustment during posture change (orthostatic dysregulation: OD) which is characterized by instantaneous orhthostatic hypotension, postural tachycardia or neurally-mediated syncope. Most of the studies using power spectral analysis of heart rate variability showed sympathetic activation, however no consistent finding has been obtained. In conclusion, autonomic function might be partly involved in CFS such as OD, but its priority in causing CFS is unclear.

 

Source: Tanaka H. Autonomic function and child chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1105-12. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561705

 

Childhood chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome in childhood and adolescents(CCFS) is a complex and debilitation with severe morbidity and confusion. It is common condition with up to 3-5% of children and adolescents showing strange fatigue and confusion for more than 30 days. In this condition, four major symptoms are important: sleep disorders, easy fatigability, disturbed learning and memorization and immunological problems. Routine laboratory studies are similar to adult CFS, although abnormalities can be seen on serum pyruvic acid level, OGTT pattern, deep body temperature rhythm, hormonal secretion rhythm, and cerebral blood flow. For a diagnosis of CCFS, a research group supported by Japanese ministry of health, labor and welfare developed CCFS case definition on 2004. Treatment focused to correct disrupted circadian rhythms and supply of energy.

 

Source: Miike T. Childhood chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1099-104. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561704

 

Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents

Abstract:

In the adolescent population, fatigue is associated with somatic complaints, unrefreshing sleep, cognitive disturbances and symptoms of depression and anxiety. This pattern of symptoms resembles the one described in chronic fatigue syndrome (CFS). Since immunological alterations have been reported in CFS patients, we wondered whether also severely fatigued girls from a healthy population would show comparable alterations in psychological and immunological parameters. We tested this hypothesis in a longitudinal design, allowing a reliable assessment of the participants’ characteristic immune status. Groups of severely fatigued (N=67) and non-fatigued (N=61) participants were selected. Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep quality, and somatic and CFS-related symptoms than non-fatigued participants across three measurements during one year (T1: spring, T2: autumn, T3: spring). In contrast, no group differences in mitogen-induced cytokine production or T-cell proliferation in vitro or in leukocyte subset counts were observed. Although absolute cytokine production and cell counts were affected by seasonal variation, the within-subject values, relatively to the rest of the participants, were fairly stable. Data from a small group of CFS patients (N=11) showed similarities in self-reported complaints between CFS patients and fatigued participants. Interestingly, CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed. These results show that, although overlap in symptomatology between the general population and patients with CFS was observed, only CFS patients show a skewing of the cytokine balance towards an anti-inflammatory profile.

 

Source: ter Wolbeek M, van Doornen LJ, Kavelaars A, van de Putte EM, Schedlowski M, Heijnen CJ. Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents.Brain Behav Immun. 2007 Nov;21(8):1063-74. Epub 2007 Jun 1. https://www.ncbi.nlm.nih.gov/pubmed/17544255