Orthostatic intolerance & Postural orthostatic tachycardia syndrome (POTS) & Low blood volume

(a) Orthostatic intolerance & Postural orthostatic tachycardia syndrome (POTS) & Low blood volume

(b) Water-loading tests (urinary output)


(a) Orthostatic intolerance & Postural orthostatic tachycardia syndrome (POTS) & Low blood volume

  • Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome.>Ocon AJ, Messer ZR, Medow MS, Stewart JM. Department of Physiology, New York Medical College, Valhalla, NY, USA. anthony_ocon@nymc.edu. Clin Sci (Lond). 2012 Mar;122(5):227-38. .
  • Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome. Julian M. Stewart, Marvin S. Medow, Zachary R. Messer, Ila L. Baugham, Courtney Terilli, and Anthony J. Ocon. Integrative Cardiovascular Physiology and Pathophysiology, December 2011.
  • J Pediatr. 1999 Oct;135(4):494-9. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, Geraghty MT.
  • Impaired blood pressure variability in chronic fatigue syndrome—a potential biomarker. Newton et al. QJM doi: 10.1093/qjmed/hcs085
  • Dr. Julia Newton, Newcastle University, UK (a leading international expert in this area)

    • BP, HRV, Tilt table testing (HUT), and impedance cardiography. The objective is to identify Neurally mediated hypotension and POTS. The valsalva manoeuvre is used in some studies. Liver and BP are inter-related. During valsalva test, the liver volume changes dramatically in ME. Using cardiac MRI, 1/3 ME patients had a significant PCr/ATP value of less than 1.6. There was exaggerated torsion of the left ventricle during pumping.  These measures confirm autonomic abnormalities in ME, with associated brain, cardiac and muscle abnormalities. See Dr. Julia Newton's presentation at International ME Conference 2014

    • Autonomic Test. The following is taken from research by Professor Julian Newton, University of Newcastle. Markers - "At rest, LF-HRV (sympathetic) was significantly increased in CFS compared to controls, while parasympathetic markers were significantly reduced (P = 0.006). Total DBP spectral power was increased (P = 0.0003) across all domains, with a shift towards sympathetic and away from parasympathetic SBPV (P = 0.05). On standing, overall SBPV response was significantly reduced with reductions in both sympathetic and parasympathetic components of SBPV (all P < 0.0001). Change in LF-DBP and relative balance of LF/HF DBP on standing differed between CFS and controls (P < 0.0001). Using the 85% sensitivity levels, we determined a threshold for three chosen resting BPV parameters of LF DBP >3.185, rest HF DBP >0.86, rest total DBP >7.05. Achieving all of these differentiated between CFS and controls with 77% sensitivity and 53% specificity."
      Source: Impaired blood pressure variability in chronic fatigue syndrome—a potential biomarker. Newton et al. QJM doi: 10.1093/qjmed/hcs085

    • Other Orthostatic Intolerance and POTS tests involving (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.
      Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. Ieuan Lewis, Jessie Pairman, Gavin Spickett, Julia L Newton. Journal of Internal Medicine.

    • Impaired peripheral pulse characteristics on orthostasis
      Allen J, Murrary A, Di Maria C, Newton JL: Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis - a new potential diagnostic biomarker. Physiol Meas 2010, 33:231-241.
  • Farquhar WB, Hunt BE, Taylor JA, Darling SE, Freeman R (2002), "Blood volume and its relation to peak O2 consumption and physical activity in patients with chronic fatigue", Am J Physiol Heart Circ Physiol, Jan;282(1):H66-71,
  • Miwa, K. and Fujita, M. (2011), Small Heart With Low Cardiac Output for Orthostatic Intolerance in Patients With Chronic Fatigue Syndrome. Clin Cardiol, 34: 782–786. doi: 10.1002/clc.20962. Exp Biol Med (Maywood). 2003 Feb;228(2):167-74.
  • A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome. Yamamoto Y, LaManca JJ, Natelson BH.
  • Hurum, H., Sulheim, D., Thaulow, E. and Wyller, V. B. (2011), Elevated nocturnal blood pressure and heart rate in adolescent chronic fatigue syndrome. Acta Paediatrica, 100: 289–292. doi: 10.1111/j.1651-2227.2010.02073.x
  • Antibodies against receptors controlling heart rate and blood vessel vasodilation and constriction
    The antibodies and biological markers are outlined in the following paper below. Commercial tests are being developed for this.
    Autoimmune Basis for Postural Tachycardia Syndrome.Hongliang et al.. J Am Heart Assoc. 3: e000755
  • Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes
    Luis E. Okamoto, Satish R. Raj, Amanda Peltier, Alfredo Gamboa, Cyndya Shibao, André Diedrich, Bonnie K. Black, David Robertson, and Italo Biaggioni. Clin Sci (Lond). 2012 February 1; 122(Pt 4): 183–192.
  • Freeman R, Komaroff AL: Does the chronic fatigue syndrome involve the autonomic nervous system? Am J Med 1997, 102:357-364.
  • Allen J, Murrary A, Di Maria C, Newton JL: Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis - a new potential diagnostic biomarker. Physiol Meas 2010, 33:231-241.

  • Newton JL, Okonkwo O, Sutcliffe K, Seth A, Shin J, Jones DEJ: Symptoms of autonomic dysfunction in chronic fatigue syndrome. Q J Med 2007, 100:519-526.

  • Mosqueda Garcia R, Furlan R, Snell M, Jacob G, Harris P: Primary sympathetic hyperadrenergic orthostatic tachycardia syndrome (HOT). Neurology 1997, 48:A147.

  • Pagani M, Lucini D, Mela GS, Langewitz W, Malliani A: Sympathetic overactivity in subjects complaining of unexplained fatigue. Clin Sci 1994, 87:655-661.

  • Fessel J, Robertson D (2006), "Orthostatic hypertension: when pressor reflexes overcompensate", Nat Clin Pract Nephrol Aug;2(8):424-31
  • De Becker P, Dendale P, De Meirleir K, Campine I, Vandenborne K, Hagers Y: Autonomic testing in patients with chronic fatigue syndrome. Am J Med 1998, 105:122S-126S.
  • Soetekouw PM, Lenders JW, Bleijenberg G, Thien T, van der Meer JW: Autonomic function in patients with chronic fatigue syndrome. Clin Auton Res 1999, 9:334-340.

  • Cerebral vascular control is associated with skeletal muscle pH in chronic fatigue syndrome patients both at rest and during dynamic stimulation.
    He J, Hollingsworth KG, Newton JL, Blamire AM. Neuroimage (Amst). 2013 Jan 5;2:168-73
  • The Importance of Orthostatic Intolerance in the Chronic Fatigue Syndrome
    by Ronald Schondorf phD, MD and Roy Freeman MD
    From the Autonomic ReflexLaboratory, Dept. of Neurology, McGill University, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada and the autonomic
    and Peripheral Nerve Laboratory, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
    This work supported by CFIDS Association of America (RS) and National Institutes
    of Health Grant R01-HL5g459.
  • Rowe PC, Boo-Holaigh I, Kan JS, Calkins H: Is neurally mediated hypotension an unrecognized cause of chronic fatigue? Lancet 1995, 345:623-624

  • Hollingsworth KG, Jones DE, Taylor R, Blamire AM, Newton JL. Impaired cardiovascular response to standing in chronic fatigue syndrome. Eur J Clin Invest. 2010;40:608–15.
  • Bou-Holaigh I, Rowe PC, Kan JS, Calking H: The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA 1995, 274:961-967.

  • Streeten DH, Anderson GH Jr: The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res 1998, 8:119-124.

  • Schondorf R, Freeman R: The importance of orthostatic intolerance in the chronic fatigue syndrome. Am J Med Sci 1999, 317:117-123.

  • Axelrod FB, Chelimsky GG, Weese-Mayer DE: Pediatric autonomic disorders. Pediatrics 2006, 2006:309-321.

  • Stewart J, Weldon A, Arlievsky N, Li K, Munoz J: Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt table testing in children with chronic fatigue syndrome. Clin Auton Res 1998, 8:221-230.

  • Stewart JM, Gewitz MH, Weldon A, Munoz J: Patterns of orthostatic intolerance: the orthostatic tachycardia syndrome and adolescent chronic fatigue. J Pediatr 1999, 135:218-225.

  • Stewart JM: Autonomic nervous system dysfunction in adolescents with postural orthostatic tachycardia syndrome and chronic fatigue syndrome is characterized by attenuated vagal baroreflex and potentiated sympathetic vasomotion. Pediatr Res 2000, 48:218-226.

  • Along with the world renowned David H. P. Streeten, MB, DPhil, FRCP, FAAP, Dr. Bell studied 19 individuals, measuring their red blood cell (RBC) mass and plasma volume. Of the 15 female and 4 males tested, ten were found to have subnormal total blood volume and 12 were found to have low total blood volume. This high prevalence research study was published in the Journal of Chronic Fatigue Syndrome (Vol. 4(1), 1998) and will again be published for a wider audience in the American Journal of Medical Sciences. In layman's terms, this means that the average person has 5 quarts of blood in their body but those with ME/CFIDS have only 2½ quarts!
  • Bou-Houlaigah, et al. The relationship between neurally mediated hypotension and the CFS. JAMA 1995;274:961-67.
  • Gerrity TR, et al. Chronic fatigue syndrome: what role does the autonomic nervous system play in the pathophysiology of this complex illness? Neuroimmunomodulation 2002-2003;10(3):134-41. Review.
  • Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome.Hoad ASpickett GElliott JNewton J. Northern CFS/ME Clinical Network, Equinox House, Silver Fox Way, Cobalt Business Park, Newcastle upon Tyne. 2008 Dec;101(12):961-5. Epub 2008 Sep 19.



(b) Water-loading tests (urinary output)

  • ME patients results were grossly abnormal. Professor Peter Behan, The Institute of Neurological Sciences, University of Glasgow, Scotland.

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