orthostatic intolerance – Page 7 – American ME and CFS Society

Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome

Abstract:

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is considered a diagnostic marker for chronic fatigue syndrome (CFS).

OBJECTIVES: The aims of this study were to (i) compare POTS prevalence in a CFS cohort with fatigued patients not meeting CFS criteria, and (ii) assess activity, impairment and response to cognitive behavioural therapy (CBT) in CFS patients with POTS (POTS-CFS) and without POTS (non-POTS-CFS).

METHODS: Prospective cohort study at the Radboud University Medical Centre in the Netherlands. Between June 2013 and December 2014, 863 consecutive patients with persistent fatigue were screened. Patients underwent an active standing test, filled out questionnaires and wore an activity-sensing device for a period of 12 days.

RESULTS: A total of 419 patients with CFS and 341 non-CFS fatigued patients were included in the study. POTS prevalence in adult patients with CFS was 5.7% vs. 6.9% in non-CFS adults (P = 0.54). In adolescents, prevalence rates were 18.2% and 17.4%, respectively (P = 0.93). Adult patients with POTS-CFS were younger (30 ± 12 vs. 40 ± 13 years, P = 0.001) and had a higher supine heart rate (71 ± 11 vs. 65 ± 9 beats per min, P = 0.009) compared with non-POTS-CFS patients. Severity and activity patterns did not differ between groups. In patients with CFS, criteria for Systemic Exertion Intolerance Disease (SEID) were met in 76% of adults and 67% of adolescents. In these patients with CFS fulfilling the SEID criteria, the prevalence of POTS was not different from that in the overall CFS population. POTS-CFS adolescents had less clinically significant improvement after CBT than non-POTS-CFS adolescents (58% vs. 88%, P = 0.017).

CONCLUSION: In adults with CFS, the prevalence of POTS was low, was not different from the rate in non-CFS fatigued patients and was not related to disease severity or treatment outcome. In POTS-CFS adolescents, CBT was less successful than in non-POTS-CFS patients. The evaluation of POTS appears to be of limited value for the diagnosis of CFS.

Source: Roerink ME, Lenders JW, Schmits IC, Pistorius AM, Smit JW, Knoop H, van der Meer JW. Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome. J Intern Med. 2017 Feb;281(2):179-188. doi: 10.1111/joim.12564. Epub 2016 Oct 2. https://www.ncbi.nlm.nih.gov/pubmed/27696568

Down-regulation of renin-aldosterone and antidiuretic hormone systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

BACKGROUND: Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been postulated as the cause of chronic fatigue syndrome (CFS). A small heart or reduced left ventricular volume with reduced cardiac output has been reported to be common in patients with ME. The main circulatory blood volume regulators may be down-regulated.

METHODS: Plasma levels of the neurohumoral factors that regulate circulatory blood volume were determined in 18 patients with ME and 15 healthy subjects (Controls).

RESULTS: The echocardiographic examination revealed that the mean values for the left ventricular end-diastolic diameters, stroke volume index, and cardiac index as well as the mean blood pressure were all significantly smaller in the ME group than in the Controls. The mean plasma renin activity (1.6±1.0ng/ml/h vs. 2.5±1.5ng/ml/h, p=0.06) was considerably lower in the ME group than in the Controls. Both the mean plasma aldosterone (104±37pg/ml vs. 157±67pg/ml, p=0.004) and antidiuretic hormone (ADH) (2.2±1.0pg/ml vs. 3.3±1.5pg/ml, p=0.02) concentrations were significantly lower in the ME group than in the Controls.

Desmopressin (120μg), a synthetic version of arginine vasopressin, was orally administered for five successive days to 10 patients with ME. In five patients (50%), the symptoms of orthostatic intolerance during a 10min active standing test were ameliorated in association with a significant increase in urinary osmotic pressure and decrease in heart rate. Furthermore, in five patients (50%), the performance status scores for the activities of daily living were improved.

CONCLUSIONS: Both the renin-aldosterone and ADH systems were down-regulated despite the existence of reduction in cardiac preload and output in patients with ME. Desmopressin improved symptoms in half of the patients.

Source: Miwa K. Down-regulation of renin-aldosterone and antidiuretic hormone systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome. J Cardiol. 2016 Jul 8. pii: S0914-5087(16)30120-4. doi: 10.1016/j.jjcc.2016.06.003. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27401397

Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance

Abstract:

Central nervous system dysfunction with myalgic encephalomyelitis (ME) has been suggested as the main cause of chronic fatigue syndrome. Fluctuation of the symptom severity and hierarchy is a characteristic feature in ME patients. The characteristics of the sympathetic activation may differ between the “good days” and “bad days” in them.

Twenty-four ME patients with orthostatic intolerance underwent a conventional 10-min active standing test and echocardiography both on a “good day” and a “bad day”, defined according to the severity of their symptoms. The mean heart rate at rest was significantly higher on the “bad days” than on the “good days”. During the standing test on a “bad day”, 5 patients (21 %) failed to maintain an upright posture for 10 min, whereas on a “good day” all the 24 patients maintained it.

Postural orthostatic tachycardia (POT) (increase in heart rate ≥30 beats/min) or severe POT (heart rate ≥120 beats/min) was observed on the “bad days” in 10 patients (43 %) who did not suffer from the severe tachycardia on the “good days”, suggesting the exaggerated sympathetic nervous activation.

In contrast, POT did not occur or severe POT was attenuated on the “bad days” in 5 patients (21 %) who developed POT or severe POT on the “good days”, suggesting the impaired sympathetic activation. Echocardiography revealed significantly lower mean values of both the left ventricular end-diastolic diameter and stroke volume index on the “bad days” compared with the “good days”.

In conclusion, in ME patients with orthostatic intolerance, the exaggerated activation of the sympathetic nervous system while standing appears to switch to the impaired sympathetic activation after the system is loaded with the additional accentuated stimuli associated with the preload reduction.

Source: Miwa K. Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance. Heart Vessels. 2016 Sep;31(9):1522-8. doi: 10.1007/s00380-015-0744-3. Epub 2015 Sep 15. https://www.ncbi.nlm.nih.gov/pubmed/26374335

Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A-adrenoceptor agonist clonidine.

METHODS: A total of 176 adolescent CFS patients (12-18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules (25 μg or 50 μg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model.

RESULTS: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment. There were 14 drop-outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation of all RR-intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20° head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period.

CONCLUSIONS: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance.

TRIAL REGISTRATION: Clinical Trials ID: NCT01040429, date of registration 12/28/2009.

Source: Fagermoen E, Sulheim D, Winger A, Andersen AM, Gjerstad J, Godang K, Rowe PC, Saul JP, Skovlund E, Wyller VB. Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. BMC Pediatr. 2015 Sep 10;15:117. doi: 10.1186/s12887-015-0428-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566847/ (Full article)

Timed loaded standing in female chronic fatigue syndrome compared with other populations

Erratum in

J Rehabil Res Dev. 2015;52(7):859.

Abstract:

Patients with chronic fatigue syndrome (CFS), like patients with osteoporosis, have similar difficulties in standing and sitting. The aim of the study was to compare combined trunk and arm endurance among women with CFS (n = 72), women with osteoporosis (n = 30), nondisabled women (n = 55), and women from non-industrialized countries (n = 58) using the timed loaded standing (TLS) test. TLS measures how long a person can hold a 1 kg dumbbell in each hand in front of him or her with straight arms. TLS was higher in the industrialized nondisabled population than in the non-industrialized study population (p < 0.001) and in patients with osteoporosis (p = 0.002).

TLS was lower in patients with CFS than in nondisabled controls (p < 0.001). After adjusting for age, body height, and weight, combined trunk and arm endurance was lower in CFS patients than in osteoporotic patients, even though the patients with osteoporosis were more than 25 yr older (p < 0.001) [corrected]. In CFS, TLS was lower than in the non-industrialized group (p = 0.02). Since only women were studied, external validity of the results is limited to adult female patients with CFS. TLS revealed a specific biomechanical weakness in CFS patients that can be taken into account from the onset of a rehabilitation program. We propose that influencing the quality, rather than the quantity, of movement could be used in the rehabilitation.

Source: Eyskens JB, Nijs J, D’Août K, Sand A, Wouters K, Moorkens G. Timed loaded standing in female chronic fatigue syndrome compared with other populations. J Rehabil Res Dev. 2015;52(1):21-9. doi: 10.1682/JRRD.2014.03.0086. http://www.rehab.research.va.gov/jour/2015/521/JRRD-2014-03-0086.html (Full article)

Orthostatic responses in adolescent chronic fatigue syndrome: contributions from expectancies as well as gravity

Abstract:

BACKGROUND: Orthostatic intolerance is common in chronic fatigue syndrome (CFS), and several studies have documented an abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli. The aim of this study was to explore whether the expectancies towards standing are contributors to autonomic responses in addition to the gravitational stimulus itself.

METHODS: A total of 30 CFS patients (12-18 years of age) and 39 healthy controls underwent 20° head-up tilt test and a motor imagery protocol of standing upright. Beat-to-beat cardiovascular variables were recorded.

RESULTS: At supine rest, CFS patients had significantly higher heart rate, diastolic blood pressure, and mean arterial blood pressure, and lower stroke index and heart rate variability (HRV) indices. The response to 20° head-up tilt was identical in the two groups. The response to imaginary upright position was characterized by a stronger increase of HRV indices of sympathetic predominance (power in the low-frequency range as well as the ratio low-frequency: high-frequency power) among CFS patients.

CONCLUSIONS: These results suggest that in CFS patients expectancies towards orthostatic challenge might be additional determinants of autonomic cardiovascular modulation along with the gravitational stimulus per se.

Source: Wyller VB, Fagermoen E, Sulheim D, Winger A, Skovlund E, Saul JP. Orthostatic responses in adolescent chronic fatigue syndrome: contributions from expectancies as well as gravity. Biopsychosoc Med. 2014 Sep 15;8:22. doi: 10.1186/1751-0759-8-22. eCollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166398/ (Full article)

Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle

Abstract:

The etiology of chronic fatigue syndrome (CFS) is unknown. Myalgic encephalomyelitis (ME) has been recently postulated to be the cause of CFS. Orthostatic intolerance (OI) has been known as an important symptom in predicting quality of life in CFS patients. Cardiac function may be impaired in patients with ME.

The presence or absence of OI was determined both symptomatically and by using a 10-min stand-up test in 40 ME patients. Left ventricular (LV) dimensions and function were determined echocardiographically in the ME patients compared to 40 control subjects.

OI was noted in 35 (97%) of the 36 ME patients who could stand up quickly. The mean values for the cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic diameter (EDD), LV end-systolic diameter, stroke volume index, cardiac index and LV mass index were all significantly smaller in the ME group than in the controls. Both a small LVEDD (<40 mm, 45 vs. 3%) and a low cardiac index (<2 l/ min/mm2, 53 vs. 8%) were significantly more common in the ME group than in the controls. Both heart rate and LV ejection fraction were similar between the groups.

In conclusion, a small LV size with a low cardiac output was common in ME patients, in whom OI was extremely common. Cardiac dysfunction with a small heart appears to be related to the symptoms of ME.

Source: Miwa K. Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle. Heart Vessels. 2015 Jul;30(4):484-9. doi: 10.1007/s00380-014-0510-y. Epub 2014 Apr 16. https://www.ncbi.nlm.nih.gov/pubmed/24736946

Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration

Abstract:

We have been able to reduce substantially patient pool heterogeneity by identifying phenotypic markers that allow the researcher to stratify chronic fatigue syndrome (CFS) patients into subgroups. To date, we have shown that stratifying based on the presence or absence of comorbid psychiatric diagnosis leads to a group with evidence of neurological dysfunction across a number of spheres.

We have also found that stratifying based on the presence or absence of comorbid fibromyalgia leads to information that would not have been found on analyzing the entire, unstratified patient group. Objective evidence of orthostatic intolerance (OI) may be another important variable for stratification and may define a group with episodic cerebral hypoxia leading to symptoms.

We hope that this review will encourage other researchers to collect data on discrete phenotypes in CFS to allow this work to continue more broadly. Finding subgroups of CFS suggests different underlying pathophysiological processes responsible for the symptoms seen. Understanding those processes is the first step toward developing discrete treatments for each.

Source: Natelson BH. Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration. Front Physiol. 2013 May 20;4:109. doi: 10.3389/fphys.2013.00109. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657628/ (Full article)

Cognitive impairments associated with CFS and POTS

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue, sleep dysfunction, and cognitive deficits (Fukuda et al., 1994). Research surrounding cognitive functioning among patients with CFS has found difficulty with memory, attention, and information processing. A similar disorder, postural tachycardia syndrome (POTS), is characterized by increased heart rate, fatigue, and mental cloudiness (Raj et al., 2009). Potential implications of cognitive deficits for patients with CFS and/or POTS are discussed, including difficulties with school and/or employment.

A few biological theories (i.e., kindling, impairments in the central nervous system, and difficulty with blood flow) have emerged as potential explanations for the cognitive deficits reported in both CFS and POTS Future research should continue to examine possible explanations for cognitive impairments in CFS and POTS, and ultimately use this information to try and reduce cognitive impairments for these patients.

Source: Shanks L, Jason LA, Evans M, Brown A. Cognitive impairments associated with CFS and POTS. Front Physiol. 2013 May 16;4:113. doi: 10.3389/fphys.2013.00113. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655280/ (Full article)

Orthostatic tolerance testing in a prospective cohort of adolescents with chronic fatigue syndrome and recovered controls following infectious mononucleosis

Abstract:

Chronic fatigue syndrome (CFS) is a complex condition responsible for marked functional impairment. The authors recently reported that 6 months following acute infectious mononucleosis (IM), 13%, of adolescents met criteria for CFS. The authors’ objective was to assess standing orthostatic tolerance (SOT) in adolescents with CFS and in controls 6 months following IM.

In all, 36 of 39 adolescents diagnosed with CFS 6 months following IM and 43 of 50 recovered controls had SOT testing (SOTT) performed. χ(2) Analysis was performed to study the relationships between SOTT and the diagnosis of CFS. Adolescents diagnosed with CFS and recovered controls did not differ significantly in age, weight, or body mass index. The authors found that 9 of 36 adolescents with CFS (25%) versus 9 of 43 recovered controls (21%) had an abnormal SOTT, which was not a statistically significant difference. Adolescents who meet criteria for CFS 6 months following IM do not have, as a group, more standing orthostatic intolerance than recovered controls.

Source: Katz BZ, Stewart JM, Shiraishi Y, Mears CJ, Taylor R. Orthostatic tolerance testing in a prospective cohort of adolescents with chronic fatigue syndrome and recovered controls following infectious mononucleosis. Clin Pediatr (Phila). 2012 Sep;51(9):835-9. doi: 10.1177/0009922812455094. Epub 2012 Jul 31. https://www.ncbi.nlm.nih.gov/pubmed/22850676