Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome


Recent investigations suggest a role for neurally mediated hypotension (NMH) in the symptomatology of chronic fatigue syndrome (CFS) in adults. Our previous observations in children with NMH and syncope (S) unrelated to CFS indicate that the modulation of sympathetic and parasympathetic tone measured by indices of heart rate variability (HRV) is abnormal in children who faint during head-up tilt (HUT). In order to determine mine the effects of autonomic tone on HUT in children with CFS we performed measurements of HRV during HUT in 16 patients aged 11–19 with CFS. Data were compared to 26 patients evaluated for syncope and with 13 normal control subjects. After 30 minutes supine, patients were tilted to 80° for 40 minutes or until syncope occurred. Time domain indices included RR interval, SDNN, RMSSD, and pNN50. An autoregressive model was used to calculate power spectra. LFP (.04–.15 Hz), HFP (.15–.40Hz), and TP (.01–.40Hz). Data were obtained supine (baseline) and after HUT. Thirteen CFS patients fainted (CFS+, 5/13 pure vasodepressor syncope) and three patients did not (CFS-). Sixteen syncope patients fainted (S+, all mixed vasodepressor-cardioinhibitory) and 10 did not (S-). Four control patients fainted (Control+, all mixed vasodepressor-cardioinhibitory) and nine did not (Control-). Baseline indices of HRV were not different between Control+ and S+, and between Control- and S-, but were depressed in S+ compared to S-. HRV indices were strikingly decresed in CFS patients compared to all other groups. With tilt, SDNN, RMSSD, and pNN50 and spectral indices decreased in all groups, remaining much depressed in CFS compared to S or control subjects. With HUT, sympathovagal indices (LFP/HFP, nLFP, and nHFP) were relatively unchanged in CFS, which contrasts with the increase in nLFP with HUT in all other groups. With syncope RMSSD, SDNN, LFP, TP, and HFP increased in S+ (and Control+), suggesting enhanced vagal heart rate regulation. These increases were not observed in CFS+ patients. CFS is associated with NMH during HUT in children. All indices of HRV are markedly depressed in CFS patients, even when compared with already low HRV in S+ or Control+ patients. Sympathovagal balance does not shift toward enhanced sympathetic modulation of heart rate with HUT and there is blunting in the overall HRV response with syncope during HUT. Taken together these data may indicate autonomic impairment in patients with CFS.

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  1. 1.

    Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study.Ann Intern Med 1994; 121:953–959.

    PubMed  Google Scholar 

  2. 2.

    Rowe PC, Bou-Holaigh I, Kan JS, Calkins H. Is neurally mediated hypotension an unrecognized cause of chronic fatigue?Lancet 1995; 345:623–624.

    Article  PubMed  Google Scholar 

  3. 3.

    Bou-Holaigh I, Rowe PC, Kan JS, Calkins H. The relationship between neurally mediated hypotension and the chronic fatigue syndrome.JAMA 1995; 274:961–967.

    Article  PubMed  Google Scholar 

  4. 4.

    Assessment: Clinical autonomic testing report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.Neurology 1991; 46:873–880.

  5. 5.

    Stewart JM, Erb M, Sorbera C. Heart rate variability and the outcome of head-up tilt in syncopal children.Pediat Res 1996; 5:702–709.

    Google Scholar 

  6. 6.

    Balaji Soslizlok PC, Allen MC, Mckay CA, Gillette PC. Neurocardiogenic syncope in children with a normal heart.JACC 1994; 23:779–785.

    PubMed  Google Scholar 

  7. 7.

    Perry JC, Garson A. The child with recurrent syncope: autonomic function testing and beta-adrenergic hypersensitivity.JACC 1991; 17:1168–1171.

    PubMed  Google Scholar 

  8. 8.

    Baharav A, Mimouni M, Lehrman-Sagie T, Izraeli S, Akselrod S. Spectral analysis of heart rate in vasovagal syncope: the autonomic nervous system in vasovagal syncope.Clin Auton Res 1993; 3:261–269.

    Article  PubMed  Google Scholar 

  9. 9.

    Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart Rate Variability: Standards of Measurement, Physiological Interpretation, and clinical use.Circulation. 1996; 93:1043–1065.

    Google Scholar 

  10. 10.

    Montano N, Ruscone TG, Porta A, Lombardi F, Pagani M, Malliani A. Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt.Circulation 1994; 90:1826–1831.

    Google Scholar 

  11. 11.

    Pagani M, Lombardi F, Guzzeti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell'Orto S, Piccaluga E, Turiel M, Baselli G, Cerutti S, Malliani A. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympathovagal interaction in man and conscious dog.Circ Res 1986; 59:178–193.

    Google Scholar 

  12. 12.

    Kay SM, Marple SL. Spectrum analysis—a modern perspective.Proceed IEEE 1981; 69:1380–1419.

    Google Scholar 

  13. 13.

    Yataco A, Rowe P, Kass DA, Berger RD, Calkins H. Comparison of heart rate variability in patients with chronic fatigue syndrome and controls.Clin Auton Res 1997; 7:293–297.

    PubMed  Google Scholar 

  14. 14.

    Sneddon JF, Counihan PJ, Bashir Y, Haywood GA, Ward DE, Camm AJ. Assessment of autonomic function in patients with neurally mediated syncope: augmented cardiopulmonary baroreceptor responses to graded orthostatic stress.JACC 1993; 21:1193–1198.

    PubMed  Google Scholar 

  15. 15.

    Smets SMA, Garssen B, Bonke B, DeHaes JCJM. The multidimensional fatigue inventory (MFI) Psychometric qualities of an instrument to assess fatigue.J Psychosom Res 1995; 39:315–325.

    Article  PubMed  Google Scholar 

  16. 16.

    Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale.J Psychosom Res 1993; 37:147–53.

    Article  PubMed  Google Scholar 

  17. 17.

    Plioplys AV, Plioplys S. Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome.Neuropsychobiology 1995; 32:175–81.

    PubMed  Google Scholar 

  18. 18.

    Barnes PR, Taylor DJ, Kemp GJ, Radda GK. Skeletal muscle bioenergetics in the chronic fatigue syndrome.J Neurol Neurosurg Psych 1993; 56:679–83.

    Google Scholar 

  19. 19.

    Edwards RH, Gibson H, Clague JE, Helliwell T. Muscle histopathology and physiology in chronic fatigue syndrome.Ciba Found Symp 1993; 173:102–31.

    PubMed  Google Scholar 

  20. 20.

    Stokes MJ, Cooper RG, Edwaurds RH. Normal muscle strength and fatiguability in patients suffering with effort syndromes.Br Med J 1988; 297:1014–1017.

    Google Scholar 

  21. 21.

    Byrne E, Trounce I. Chronic fatigue and myalgia syndrome: mitochondrial and glycolytic studies in skeletal muscle.J Neurol Neurosurg Psych 1987; 50:743–746.

    Google Scholar 

  22. 22.

    Stokes J, Jamal GA, Hansen S. Electrophysiological studies in the post-viral fatigue syndrome.J Neurol Neurosurg Psych 1985; 48:691–694.

    Google Scholar 

  23. 23.

    Montague TJ, Marrie TJ, Klassen GA, Bewick DJ, Horacek BM. Cardiac function at rest and with exercise in the chronic fatigue syndrome.Chest 1989; 95:779–84.

    PubMed  Google Scholar 

  24. 24.

    Swanink CM, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM. Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay.Clin Infect Dis 1995; 20:1390–2.

    PubMed  Google Scholar 

  25. 25.

    Clements GB, McGarry F, Naim C, Galbraith DN. Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue.J Med Virol 1995; 45:1561–61.

    Google Scholar 

  26. 26.

    Manian FA. Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?Clin Infect Dis 1994; 19:448–53.

    PubMed  Google Scholar 

  27. 27.

    Costa DC, Tannock C, Brostoff J. Brainstem perfusion is impaired in chronic fatigue syndrome.QJM 1995; 88:767–73.

    PubMed  Google Scholar 

  28. 28.

    Schwartz RB, Garada BM, Komaroff AL, Tice HM, Gleit M, Jolesz FA, Holman BL. Detection of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and SPECT.Am J Roentgenol 1994; 162:935–941.

    Google Scholar 

  29. 29.

    Sisto SA, Tapp W, Drastal S, Bergen M, DeMasi I, Cordero D, Natelson B. Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome.Clin Auton Res 1995; 5:139–43.

    Article  PubMed  Google Scholar 

  30. 30.

    McComas AJ, Miller RG, Gandevia SC. Fatigue brought on by malfunction of the central and peripheral nervous systems.Adv Exp Med Biol 1995; 384:495–512.

    PubMed  Google Scholar 

  31. 31.

    Kent Braun JA, Sharma KR, Weiner MW, Massie B, Miller RG. Central basis of muscle fatigue in chronic fatigue syndrome.Neurology 1993; 43:125–31.

    PubMed  Google Scholar 

  32. 32.

    Cleare AJ, Bearn J, Allain T, McGregor A, Wessely S, Murray RM, O'Keane V. Contrasting neuroendocrine responses in depression and chronic fatigue.J Affect Disord 1995; 34:283–9.

    Article  PubMed  Google Scholar 

  33. 33.

    Lieberman J, Bell DS. Serum angiotensin-converting enzyme as a marker for the chronic fatigue-immune dysfunction syndrome: a comparison to serum angiotensin-converting enzyme in sarcoidosis.Am J Med 1993; 95:407–12.

    Article  PubMed  Google Scholar 

  34. 34.

    Bakheit AM, Behan PO, Watson WS, Morton JJ. Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome.Acta Neurol Scand 1993; 87:234–8.

    PubMed  Google Scholar 

  35. 35.

    Benditt DG, Ferguson DW, Grubb BP, Kapoor WN, Kugler J, Lerman BB, Maloney JD, Raviele A, Ross B, Sutton R, Wolk MJ, Wood DL. Titt Table Testing for assessing syncope ACC expert consensus document.JACC 1996; 23:263–275.

    Google Scholar 

  36. 36.

    Sander Jensen K, Secher NH, Atrup A, Christensen NJ, Giese J, Schwartz TW, Warberg J, Bie P. Hypotension induced by passive head-up tilt: endocrine and cirulatory mechanisms.Am J Physiol 1986; 251:R742–8.

    PubMed  Google Scholar 

  37. 37.

    Morillo CA, Klein GJ, Jones DL, Yee R. Time and frequency domain analyses of heart rate variability during orthostatic stress in patients with neurally mediated syncope.Am J Cardiol 1994; 74:1258–1262.

    Article  PubMed  Google Scholar 

  38. 38.

    Korkushko OV, Shatilo VB, Plachinda YI, Shatilo TV. Autonomic control of cardiac chronotropic function in man as a function of age: assessment by power spectral analysis of heart rate variability.J Auton Nerv Syst 1991; 32:191–198.

    Article  PubMed  Google Scholar 

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Correspondence to Dr. Julian Stewart.

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Stewart, J., Weldon, A., Arlievsky, N. et al. Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome. Clinical Autonomic Research 8, 221–230 (1998).

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  • heart rate variability
  • chronic fatigue syndrome
  • child