Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope

Abstract:

OBJECTIVES: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF).

PATIENTS AND METHODS: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation.

RESULTS: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients.

CONCLUSIONS: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.

 

Source: Naschitz JE, Mussafia-Priselac R, Kovalev Y, Zaigraykin N, Slobodin G, Elias N, Rosner I. Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope. Am J Med Sci. 2006 Jun;331(6):295-303. https://www.ncbi.nlm.nih.gov/pubmed/16775435

 

Orthostatic instability in a population-based study of chronic fatigue syndrome

Abstract:

PURPOSE: Autonomic nervous system dysfunction has been suggested as involved in the pathophysiology of chronic fatigue syndrome. This population-based case control study addressed the potential association between orthostatic instability (one sign of dysautonomia) and chronic fatigue syndrome.

SUBJECTS AND METHODS: Fifty-eight subjects who fulfilled criteria of the 1994 chronic fatigue syndrome research case definition and 55 healthy controls participated in a 2-day inpatient evaluation. Subjects had been identified during a 4-year population-based chronic fatigue syndrome surveillance study in Wichita, Kan. The present study evaluated subjects’ current medical and psychiatric status, reviewed past medical/psychiatric history and medication use, used a stand-up test to screen for orthostatic instability, and conducted a head-up tilt table test to diagnose orthostatic instability.

RESULTS: No one manifested orthostatic instability in the stand-up test. The head-up tilt test elicited orthostatic instability in 30% of eligible chronic fatigue syndrome subjects (all with postural orthostatic tachycardia) and 48% of controls (50% with neurally mediated hypotension); intolerance was present in only nonfatigued (n=7) subjects. Neither fatigue nor illness severity were associated with outcome.

CONCLUSIONS: Orthostatic instability was similar in persons with chronic fatigue syndrome and nonfatigued controls subjects recruited from the general Wichita population. Delayed responses to head-up tilt tests were common and may reflect hydration status. These findings suggest reappraisal of primary dysautonomia as a factor in the pathogenesis of chronic fatigue syndrome.

Comment in: Orthostatic intolerance in chronic fatigue syndrome. [Am J Med. 2007]

 

Source: Jones JF, Nicholson A, Nisenbaum R, Papanicolaou DA, Solomon L, Boneva R, Heim C, Reeves WC. Orthostatic instability in a population-based study of chronic fatigue syndrome. Am J Med. 2005 Dec;118(12):1415. http://www.ncbi.nlm.nih.gov/pubmed/16378795

 

Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome

Abstract:

Although a number of studies have reported alterations in cardiac autonomic nervous system function in chronic fatigue syndrome (CFS), the results are not consistent across studies. Reasons for these discrepancies include (1) the use of a heterogeneous patient sample that included those with orthostatic postural tachycardia (POTS), a condition with an autonomic changes, and (2) the use of frequency domain techniques which require a stationary signal and averaging data across relatively long epochs.

To deal with these shortcomings, we used the smoothed pseudo-Wigner-Ville transform (SPWVT) to analyze heart rate variability (HRV) and blood pressure variability (BPV) during head-up tilt (HUT) by separating CFS patients into those with and without POTS. SPWVT has the advantage of providing instantaneous information about autonomic function under nonstable physiological conditions. We studied 18 CFS patients without POTS, eight CFS patients with POTS and 25 sedentary healthy controls during supine rest and during the first 10 min after HUT.

While we found significant effects of postural change in both groups for all autonomic variables, there were significant group x time interactions between CFS without POTS and controls for only instant center frequency (ICF) within the low frequency region both from HRV (p=0.02) and from BPV (p=0.01). Although the physiological meaning of ICF still remains unknown, the data suggest that even CFS patients without POTS may have a subtle underlying disturbance in autonomic function.

 

Source: Yoshiuchi K, Quigley KS, Ohashi K, Yamamoto Y, Natelson BH. Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome. Auton Neurosci. 2004 Jun 30;113(1-2):55-62. http://www.ncbi.nlm.nih.gov/pubmed/15296795

 

The head-up tilt test in the diagnosis and management of chronic fatigue syndrome

Fatigue, as a symptom, refers to a sense of lethargy or loss of energy. Fatigue is common in infections, endocrine disorders, heart failure, chronic diseases of the lungs, liver or kidneys, malignancies, anemia, nutritional deficits, inflammatory arthritis, Parkinson’s disease, depression, anxiety states, effect of certain medications, or drug withdrawal [1]. Population-based studies show that fatigue is one of the most common somatic symptoms, with as much as 20± 30% of the population complaining of chronic fatigue [2]. Only a small fraction of these satisfy the clinical definition criteria for chronic fatigue syndrome [1].

You can read the rest of this article here: https://www.ima.org.il/FilesUpload/IMAJ/0/54/27402.pdf

 

Source: Naschitz JE, Sabo E, Dreyfuss D, Yeshurun D, Rosner I. The head-up tilt test in the diagnosis and management of chronic fatigue syndrome. Isr Med Assoc J. 2003 Nov;5(11):807-11. https://www.ima.org.il/FilesUpload/IMAJ/0/54/27402.pdf (Full article)

 

The head-up tilt test for diagnosing chronic fatigue syndrome

Comment on: The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. [QJM. 2003]

 

Sir,

The recent paper by Naschitz et al.  on the use of the head‐up tilt test with haemodynamic instability score (HIS) in the diagnosis of chronic fatigue syndrome (CFS) provides additional insight about the role of dysautonomia in the pathogenesis of CFS. We would like to raise some points regarding the patient group studied.

The enrolment of clinically‐diagnosed CFS patients and the awareness of diagnosis by technicians prior to performing the tilt test, could result in selection bias. Additionally, generalizing the result of the study, whose population was rich in patients with CFS (40/349, or 11%) to the general population (prevalence of CFS 0.07–0.2%) could be misleading. Using their results of a sensitivity of 90.3% and specificity of 84.5% for a cutoff of HIS >−0.98, a positive head‐up tilt test in a patient presenting with fatigue in the general population would have a positive predictive value of only 0.37–1.15. This result, taken with the fact that around one‐fifth of the patients developed a presyncopal or syncopal episode, would make the test less appealing to patients. However, in a patient presenting with fatigue where clinical diagnosis remained unclear despite lengthy evaluation, the head‐up tilt test could be useful for narrowing down the range of diagnoses.

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/96/5/379.2.long

 

Source: Ghosh AK, Ghosh K. The head-up tilt test for diagnosing chronic fatigue syndrome. QJM. 2003 May;96(5):379-80. http://qjmed.oxfordjournals.org/content/96/5/379.2.long (Full article)

 

Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome

Abstract:

BACKGROUND AND PURPOSE: During head-up tilt (HUT), patients with chronic fatigue syndrome (CFS) have higher rates of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS) than healthy controls. The authors studied whether patients with CFS were also more likely to have abnormal cerebral blood flow velocity (CBFV) compared with controls in response to orthostatic stress.

METHODS: Transcranial Doppler monitoring of middle cerebral artery (MCA) CBFV was performed during 3-stage HUT prospectively in 26 patients with CFS and 23 healthy controls. At the same time, continuous monitoring of arterial blood pressure (BP), heart rate (HR), endtidal CO2 (ET-CO2) were performed. Results are reported as mean +/- SD.

RESULTS: NMH developed in 21 patients with CFS and in 14 controls (P = .22). POTS was present in 9 CFS patients and 7 controls (P = .76). Supine HR was higher in CFS patients, but all other hemodynamics and CBFV measures were similar at baseline. The median time to hypotension did not differ, but the median time to onset of orthostatic symptoms was shorter in those with CFS (P < .001). The CBFV did not differ between groups in the supine posture, at 1 or 5 minutes after upright tilt, at 5 or 1 minute before the end of the test, or at termination of the test. Mean CBFV fell at termination of tilt testing in those with CFS and controls. ET-CO2 was lower at termination of the test in those with CFS versus controls (P = .002).

CONCLUSIONS: The results of this study are not consistent with the hypothesis that patients with CFS have a distinctive pattern of MCA CBFV changes in response to orthostatic stress.

 

Source: Razumovsky AY, DeBusk K, Calkins H, Snader S, Lucas KE, Vyas P, Hanley DF, Rowe PC. Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome. J Neuroimaging. 2003 Jan;13(1):57-67. http://www.ncbi.nlm.nih.gov/pubmed/12593133

 

The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome

Abstract:

BACKGROUND: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a ‘haemodynamic instability score’ (HIS).

AIM: To assess HIS sensitivity and specificity in the diagnosis of CFS.

DESIGN:  Prospective controlled study.

METHODS: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT.

RESULTS: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%.

DISCUSSION: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician’s diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.

Comment in:

The head-up tilt test for diagnosing chronic fatigue syndrome. [QJM. 2003]

Assessing chronic fatigue. [QJM. 2003]

 

Source: Naschitz JE, Rosner I, Rozenbaum M, Naschitz S, Musafia-Priselac R, Shaviv N, Fields M, Isseroff H, Zuckerman E, Yeshurun D, Sabo E. The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome.  QJM. 2003 Feb;96(2):133-42. http://qjmed.oxfordjournals.org/content/96/2/133.long (Full article)

 

A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome

Abstract:

The use of symptoms generated by head up tilt (HUT) is not a useful tool in identifying chronic fatigue syndrome (CFS). We investigated whether heart rate variability (HRV) assessed early during HUT might be useful. A sample of 46 female subjects (24 with CFS and 22 sedentary, age-matched healthy controls; CON) who had exhibited no difference in time to syncope during tilt was examined for HRV responses to 10 min of 70 degrees HUT after 5 min of baseline in the supine position. HRV data were analyzed by the method of coarse graining spectral analysis. Variables compared between groups included mean and standard deviation (SD(RRI)) of RR intervals (RRI), amplitudes of low- (A(LF); 0.04-0.15 Hz) and high-frequency (A(HF); >0.15 Hz) harmonic as well as aperiodic, fractal (A(FR); 1/f(beta)) spectral components, the spectral exponent beta, and the difference in these values between baseline and HUT for each subject.

In the supine baseline, only mean RRI was significantly (P < 0.01) lower in CFS than in CON. During HUT, however, mean RRI (P < 0.01), SD(RRI) (P < 0.01), A(HF) (P < 0.05), and A(FR) (P < 0.01) were significantly lower in CFS than in CON. When the difference in values between baseline and HUT for each subject was examined, only the difference for A(FR) (deltaA(FR)) was significantly (P < 0.01) lower in CFS than in CON, suggesting that A(FR)is a disease-specific response of HRV to HUT. When a cut-off level was set to deltaA(FR) = -2.7 msec, the sensitivity and the specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.

 

Source: Yamamoto Y, LaManca JJ, Natelson BH. A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome. Exp Biol Med (Maywood). 2003 Feb;228(2):167-74. http://www.ncbi.nlm.nih.gov/pubmed/12563023

 

Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome

Erratum in: Semin Arthritis Rheum. 2003 Apr;32(5):343. Madelain, Fields [corrected to Fields, Madeline]; Hillel, Isseroff [corrected to Isseroff, Hillel].

 

Abstract:

OBJECTIVE: In studying patients with chronic fatigue syndrome (CFS) we developed a method that confers numerical expression to the degree of blood pressure and heart rate lability, ie, the ‘hemodynamic instability score’ (HIS). The HIS in CFS patients differed significantly from healthy subjects. The present investigation compares the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope.

METHODS: Patients with CFS (n = 21), non-CFS chronic fatigue (n = 24), syncope of unknown cause (n = 44), and their age and sex-matched healthy controls (n = 21) were evaluated with a standardized head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified ‘clinical outcomes’ (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and ‘HIS endpoint’, i.e. HIS >-0.98.

RESULTS: The highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%), and healthy subjects (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of patients with non-CFS chronic fatigue, and 43% of patients with recurrent syncope. The average HIS values were: CFS = +2.02 (SD 4.07), non-CFS chronic fatigue = -2.89 (SD 3.64), syncope = -3.2 (SD 3.0), healthy = -2.48 (4.07). The odds ratios for CFS patients to have HIS >-0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients, and 34.8 compared with healthy subjects.

CONCLUSION: The cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. Apart from to these shared responses, the large majority of CFS patients exhibit a particular abnormality which is characterized by HIS values >-0.98. Thus, HIS >-0.98 lends objective criteria to the assessment of CFS.

Copyright 2002, Elsevier Science (USA). All rights reserved.

 

Source: Naschitz JE, Sabo E, Naschitz S, Rosner I, Rozenbaum M, Fields M, Isseroff H, Priselac RM, Gaitini L, Eldar S, Zukerman E, Yeshurun D. Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome. Semin Arthritis Rheum. 2002 Dec;32(3):141-8. http://www.ncbi.nlm.nih.gov/pubmed/12528078

 

Hemodynamic and neurohumoral responses to head-up tilt in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Data on the prevalence of orthostatic intolerance (OI) in patients with chronic fatigue syndrome (CFS) are limited and controversial. We tested the hypothesis that a majority of CFS patients exhibit OI during head-up tilt.

METHODS: Hemodynamic and neurohumoral responses to 40 minutes of head-up tilt were studied in 36 CFS patients and 36 healthy controls. Changes in stroke volume, cardiac output and peripheral vascular resistance were estimated from finger arterial pressure waveform analysis (Modelflow). Blood samples were drawn before and at the end of head-up tilt for measurement of plasma catecholamines.

RESULTS: At baseline, supine heart rate was higher in CFS patients (CFS: 66.4 +/- 8.4 bpm; controls: 57.4 +/- 6.6 bpm; p < 0.001) as was the plasma epinephrine level (CFS: 0.11 +/- 0.07 nmol/l; controls: 0.08 +/- 0.07 nmol/l: p = 0.015). An abnormal blood pressure and/or heart rate response to head-up tilt was seen in 10 (27.8 %) CFS patients (6 presyncope, 2 postural tachycardia, 2 tachycardia and presyncope) and 6 (16.7 %, p = 0.26) controls (5 presyncope, 1 tachycardia, 2 tachycardia and presyncope). Head-up tilt-negative CFS patients showed a larger decrease in stroke volume during tilt (-46.9 +/- 10.6) than head-up tilt-negative controls (-40.3 +/- 13.6 %, p = 0.008). Plasma catecholamine responses to head-up tilt did not differ between these groups.

CONCLUSION: Head-up tilt evokes postural tachycardia or (pre)syncope in a minority of CFS patients. The observations in head-up tilt-negative CFS patients of a higher heart rate at baseline together with a marked decrease in stroke volume in response to head-up tilt may point to deconditioning.

 

Source: Timmers HJ, Wieling W, Soetekouw PM, Bleijenberg G, Van Der Meer JW, Lenders JW. Hemodynamic and neurohumoral responses to head-up tilt in patients with chronic fatigue syndrome. Clin Auton Res. 2002 Aug;12(4):273-80. http://www.ncbi.nlm.nih.gov/pubmed/12357281