Tag: autonomic nervous system

Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review

Abstract:

INTRODUCTION: It is hypothesised that the autonomic nervous system responds differently to various stressors in patients with chronic fatigue syndrome (CFS) compared with healthy controls. The goal is to systematically review the scientific literature addressing the functioning of the autonomic nervous system in patients with CFS.

MATERIALS AND METHODS: All studies that were identified through electronic databases (PubMed and Web of Science) were screened for eligibility based on the selection criteria and assessed (two independent raters) for methodological quality using a methodological checklist for case-control studies.

RESULTS: Twenty-seven case-control studies were included. The methodological quality varied between 50% and 71·4%. Some studies showed different responses to head-up tilt and other autonomous testing.

CONCLUSION: Although comparison between the included case-control studies was difficult, we can conclude that there are differences in autonomous response between patients with CFS and healthy controls. The heart rate dynamic response during the head-up tilt test differs between patients with CFS and healthy controls, supporting the increased prevalence of postural orthostatic tachycardia syndrome. The autonomic response can be useful for the diagnosis of CFS.

© 2014 Stichting European Society for Clinical Investigation Journal Foundation.

 

Source: Van Cauwenbergh D, Nijs J, Kos D, Van Weijnen L, Struyf F, Meeus M. Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review. Eur J Clin Invest. 2014 May;44(5):516-26. doi: 10.1111/eci.12256. https://www.ncbi.nlm.nih.gov/pubmed/24601948

 

Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review

Abstract:

OBJECTIVE: The goal of this systematic literature review is to determine whether there are differences and similarities in heart rate variability (HRV) between adult patients with fibromyalgia

(FM), chronic fatigue syndrome (CFS), and healthy pain-free control subjects.

METHODS: To obtain relevant articles, PubMed and Web of Knowledge were searched for case-control studies. Selection of the literature was based on selection criteria ascertaining studies with adult human patient groups comparing HRV. Risk of bias and levels of evidence were determined.

RESULTS: Sixteen case-control studies were included, 10 comparing FM patients to controls and 6 comparing CFS patients to controls. Methodological quality was moderate to good. Both time domain and frequency domain measurements were used. The majority of the researchers observed lower HRV in FM patients compared to healthy control persons, as well as increased sympathetic activity and a blunted autonomic response to stressors. Resistance training improved HRV in FM patients. In CFS patients HRV was only reduced during sleep.

CONCLUSION: FM patients show more HRV aberrances and indices of increased sympathetic activity. Increased sympathetic activity is only present in CFS patients at night. Since direct comparisons are lacking and some confounders have to be taken into account, further research is warranted. The role of pain and causality can be subject of further research, as well as therapy studies directed to reduced HRV.

© 2013 Elsevier Inc. All rights reserved.

Comment in

Source: Meeus M, Goubert D, De Backer F, Struyf F, Hermans L, Coppieters I, De Wandele I, Da Silva H, Calders P. Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. Semin Arthritis Rheum. 2013 Oct;43(2):279-87. doi: 10.1016/j.semarthrit.2013.03.004. Epub 2013 Jul 6. https://www.ncbi.nlm.nih.gov/pubmed/23838093

 

Heart rate variability during sleep and subsequent sleepiness in patients with chronic fatigue syndrome

Abstract:

We determined whether alterations in heart rate dynamics during sleep in patients with chronic fatigue syndrome (CFS) differed from controls and/or correlated with changes of sleepiness before and after a night in the sleep laboratory. We compared beat-to-beat RR intervals (RRI) during nocturnal sleep, sleep structure, and subjective scores on visual analog scale for sleepiness in 18 CFS patients with 19 healthy controls aged 25-55 after excluding subjects with sleep disorders. A short-term fractal scaling exponent (α1) of RRI dynamics, analyzed by the detrended fluctuation analysis (DFA) method, was assessed after stratifying patients into those who reported more or less sleepiness after the night’s sleep (a.m. sleepier or a.m. less sleepy, respectively).

Patients in the a.m. sleepier group showed significantly (p<0.05) higher fractal scaling index α1 during non-rapid eye movement (non-REM) sleep (Stages 1, 2, and 3 sleep) than healthy controls, although standard polysomnographic measures did not differ between the groups. The fractal scaling index α1 during non-REM sleep was significantly (p<0.05) higher than that during awake periods after sleep onset for healthy controls and patients in the a.m. less sleepy group, but did not differ between sleep stages for patients in the a.m. sleepier group. For patients, changes in self-reported sleepiness before and after the night correlated positively with the fractal scaling index α1 during non-REM sleep (p<0.05). These results suggest that RRI dynamics or autonomic nervous system activity during non-REM sleep might be associated with disrupted sleep in patients with CFS.

Copyright © 2013 Elsevier B.V. All rights reserved.

 

Source: Togo F, Natelson BH. Heart rate variability during sleep and subsequent sleepiness in patients with chronic fatigue syndrome. Auton Neurosci. 2013 Jun;176(1-2):85-90. doi: 10.1016/j.autneu.2013.02.015. Epub 2013 Mar 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100066/ (Full article)

 

Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial

Abstract:

BACKGROUND: This pilot study (ClinicalTrials.gov ID: NCT01507701) assessed the feasibility and safety of clonidine in adolescent chronic fatigue syndrome (CFS). Specifically, we assessed clonidine dosage in relation to a) plasma concentration levels, b) orthostatic cardiovascular responses, and c) possible adverse effects.

FINDINGS: Five adolescent CFS patients (14-19 years old) received 50 μg clonidine twice per day during 14 days in an open, uncontrolled design. Plasma concentration of clonidine was assayed by standard laboratory methods. Changes in orthostatic cardiovascular responses were assessed by a 20o head-up tilt-test (HUT). Adverse effects were mapped by a questionnaire.After 14 days, C0 median (range) of clonidine was 0.21 (0.18-0.36) μg/L, and Cmax median (range) of clonidine was 0.41 (0.38-0.56) μg/L. Also, supine blood pressures and heart rate were lower during clonidine treatment, and the HUT response was closer to the normal response. No serious adverse effects were registered.

CONCLUSION: Clonidine 50 μg BID seems to be safe enough to proceed from a pilot study to a controlled trial in a select group of adolescents with CFS (ClinicalTrials.gov ID: NCT01040429).

 

Source: Fagermoen E, Sulheim D, Winger A, Andersen AM, Vethe NT, Saul JP, Thaulow E, Wyller VB. Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial. BMC Res Notes. 2012 Aug 7;5:418. doi: 10.1186/1756-0500-5-418. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461473/ (Full article)

 

Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms

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 20° 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.

 

Source: Sulheim D, Hurum H, Helland IB, Thaulow E, Wyller VB. Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms. Biopsychosoc Med. 2012 Mar 21;6:10. doi: 10.1186/1751-0759-6-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337799/ (Full article)

 

No differences in cardiovascular autonomic responses to mental stress in chronic fatigue syndrome adolescents as compared to healthy controls

Abstract:

Chronic fatigue syndrome (CFS) is a disabling disease with unknown etiology. There is accumulating evidence of altered cardiovascular autonomic responses to different somatic stressors, in particular orthostatic stress, whereas autonomic responses to mental stress remain to be investigated. In this study, we explored cardiovascular autonomic responses to a simple mental stress test in CFS patients and healthy controls.

A consecutive sample of 13 patients with CFS, aged 12 to 18 years, and a volunteer sample of 53 healthy control subjects of equal age and gender distribution were included. Blood pressure, heart rate and acral skin blood flow were continuously recorded during an arithmetic exercise.

At baseline, heart rate was significantly higher among CFS patients than controls (p = 0.02). During the arithmetic exercise, however, there were no significant differences in the responses between the two groups.

In conclusion, CFS patients have unaltered autonomic responses to simple mental stress as compared to healthy control subjects.

 

Source: Egge C, Wyller VB. No differences in cardiovascular autonomic responses to mental stress in chronic fatigue syndrome adolescents as compared to healthy controls. Biopsychosoc Med. 2010 Dec 14;4:22. doi: 10.1186/1751-0759-4-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012010/ (Full article)

 

Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress

Abstract:

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 explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS. We included a consecutive sample of 14 adolescents 12-18 years old with CFS diagnosed according to a thorough and standardized set of investigations and 56 healthy control subjects of equal sex and age distribution.

Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of -20 mmHg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.50 Hz), using an autoregressive algorithm.

Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP, compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control. CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents.

 

Source: Wyller VB, Barbieri R, Saul JP. Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress. Eur J Appl Physiol. 2011 Mar;111(3):497-507. doi: 10.1007/s00421-010-1670-9. Epub 2010 Oct 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037975/ (Full article)

 

Autonomic hyper-vigilance in post-infective fatigue syndrome

Abstract:

This study examined whether post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges.

We studied 23 patients with PIFS and 25 healthy matched control subjects. A heartbeat discrimination task and a pressure pain threshold test were used to assess interoceptive sensitivity. Cardiac response was assessed over a 4-min Stroop task. PIFS was associated with higher accuracy in heartbeat discrimination and a lower pressure pain threshold. Increased interoceptive sensitivity correlated strongly with current symptoms and potentiated differences in the cardiac response to the Stroop task, which in PIFS was characterized by insensitivity to task difficulty and lack of habituation.

Our results provide the first evidence of heightened interoceptive sensitivity in PIFS. Together with the distinct pattern in cardiac responsivity these findings present a picture of physiological hyper-vigilance and response inflexibility.

Copyright (c) 2010 Elsevier B.V. All rights reserved.

 

Source: Kadota Y, Cooper G, Burton AR, Lemon J, Schall U, Lloyd A, Vollmer-Conna U/ Autonomic hyper-vigilance in post-infective fatigue syndrome. Biol Psychol. 2010 Sep;85(1):97-103. doi: 10.1016/j.biopsycho.2010.05.009. Epub 2010 Jun 2. https://www.ncbi.nlm.nih.gov/pubmed/20678991

 

Higher heart rate and reduced heart rate variability persist during sleep in chronic fatigue syndrome: a population-based study

Abstract:

Autonomic nervous system (ANS) dysfunction has been suggested in patients with chronic fatigue syndrome (CFS). In this study, we sought to determine whether increased heart rate (HR) and reduced heart rate variability (HRV) parameters observed in CFS patients during wakefulness persist during sleep. To this end, we compared heart rate (HR) and HRV as indicators of ANS function in CFS subjects and non-fatigued (NF) controls in a population-based, case-control study.

Thirty subjects with CFS and 38 NF controls, matched for age-, sex- and body mass index, were eligible for analysis. Main outcome measures included mean RR interval (RRI), HR, and HRV parameters derived from overnight ECG. Plasma aldosterone and norepinephrine levels, medicines with cardiovascular effect, and reported physical activity were examined as covariates. General Linear Models were used to assess significance of associations and adjust for potential confounders.

Compared to controls, CFS cases had significantly higher mean HR (71.4 vs 64.8 bpm), with a shorter mean RRI [840.4 (85.3) vs 925.4(97.8) ms] (p<0.0004, each), and reduced low frequency (LF), very low frequency (VLF), and total power (TP) of HRV (p<0.02, all). CFS cases had significantly lower plasma aldosterone (p<0.05), and tended to have higher plasma norepinephrine levels. HR correlated weakly with plasma norepinephrine (r=0.23, p=0.05) and moderately with vitality and fatigue scores (r=-0.49 and 0.46, respectively, p<0.0001). Limitation in moderate physical activity was strongly associated with increased HR and decreased HRV. Nevertheless, among 42 subjects with similar physical activity limitations, CFS cases still had higher HR (71.8 bpm) than respective controls (64.9 bpm), p=0.023, suggesting that reduced physical activity could not fully explain CFS-associated differences in HR and HRV. After adjusting for potential confounders case-control differences in HR and TP remained significant (p<0.05).

CONCLUSION: The presence of increased HR and reduced HRV in CFS during sleep coupled with higher norepinephrine levels and lower plasma aldosterone suggest a state of sympathetic ANS predominance and neuroendocrine alterations. Future research on the underlying pathophysiologic mechanisms of the association is needed.

 

Source: Boneva RS, Decker MJ, Maloney EM, Lin JM, Jones JF, Helgason HG, Heim CM, Rye DB, Reeves WC. Higher heart rate and reduced heart rate variability persist during sleep in chronic fatigue syndrome: a population-based study. Auton Neurosci. 2007 Dec 30;137(1-2):94-101. Epub 2007 Sep 12. https://www.ncbi.nlm.nih.gov/pubmed/17851136

 

Symptoms of autonomic dysfunction in chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is common and its cause is unknown.

AIM: To study the prevalence of autonomic dysfunction in CFS, and to develop diagnostic criteria.

DESIGN: Cross-sectional study with independent derivation and validation phases.

METHODS: Symptoms of autonomic dysfunction were assessed using the Composite Autonomic Symptom Scale (COMPASS). Fatigue was assessed using the Fatigue Impact Scale (FIS). Subjects were studied in two groups: phase 1 (derivation phase), 40 CFS patients and 40 age- and sex-matched controls; phase 2 (validation phase), 30 CFS patients, 37 normal controls and 60 patients with primary biliary cirrhosis.

RESULTS: Symptoms of autonomic dysfunction were strongly and reproducibly associated with the presence of CFS or primary biliary cirrhosis (PBC), and correlated with severity of fatigue. Total COMPASS score >32.5 was identified in phase 1 as a diagnostic criterion for autonomic dysfunction in CFS patients, and was shown in phase 2 to have a positive predictive value of 0.96 (95%CI 0.86-0.99) and a negative predictive value of 0.84 (0.70-0.93) for the diagnosis of CFS.

DISCUSSION: Autonomic dysfunction is strongly associated with fatigue in some, but not all, CFS and PBC patients. We postulate the existence of a ‘cross-cutting’ aetiological process of dysautonomia-associated fatigue (DAF). COMPASS >32.5 is a valid diagnostic criterion for autonomic dysfunction in CFS and PBC, and can be used to identify patients for targeted intervention studies.

 

Source: Newton JL, Okonkwo O, Sutcliffe K, Seth A, Shin J, Jones DE. Symptoms of autonomic dysfunction in chronic fatigue syndrome. QJM. 2007 Aug;100(8):519-26. Epub 2007 Jul 7. http://qjmed.oxfordjournals.org/content/100/8/519.long (Full article)