ME and CFS Medical Abnormalities – Orthostatic Intolerance

 

Following is a list of articles about orthostatic intolerance in ME and CFS.

Links to the more than 1,000 peer-reviewed journal articles are listed on the M.E. and CFS Medical Abnormalities page of this website.

 

Finkelmeyer A, He J, Maclachlan L, Blamire AM, Newton JL. Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome. PLoS One. 2018 Jul 3;13(7):e0200068. PMID: 29969498

In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS.

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Miwa K, Inoue Y. The etiologic relation between disequilibrium and orthostatic intolerance in patients with myalgic encephalomyelitis (chronic fatigue syndrome). J Cardiol. 2018 Sep;72(3):261-264. PMID: 29588088

The study comprised 44 Japanese patients with ME, who underwent neurological examinations and 10-min standing and sitting tests. Symptoms of OI were detected in 40 (91%) patients and those of sitting intolerance were detected in 30 (68%). The researchers concluded that disequilibrium should be recognized as an important cause of OI and appears to be a more influential cause for OI than postural orthostatic tachycardia in patients with ME.

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Richardson AM, Lewis DP, Kita B, Ludlow H, Groome NP, Hedger MP, de Kretser DM, Lidbury BA. Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection. J Transl Med. 2018 Apr 12;16(1):97. PMID: 29650052

This study introduces the weighted standing time (WST) as a proxy for ME/CFS severity,  and investigates its behaviour in an Australian cohort. WST distribution was significantly different between ME/CFS participants and controls, with six diagnostic criteria, five analytes and one cytokine also significantly different when comparing severity via WST.

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Miwa K, Inoue Y. Truncal ataxia or disequilibrium is an unrecognised cause of orthostatic intolerance in patients with myalgic encephalomyelitis. Int J Clin Pract. 2017 Jun;71(6). PMID: 28613452

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Miwa K. Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance. Heart Vessels. 2015 Sep 15. PMID: 26374335

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.

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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. PMID: 26230614

The timed loaded standing (TLS) test scores were lower in patients with CFS than in nondisabled controls.

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Medow MS, Sood S, Messer Z, Dzogbeta S, Terilli C, Stewart JM. Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome. J Appl Physiol (1985). 2014 Nov 15;117(10):1157-64. PMID: 25277740

Compared with control subjects, CFS subjects are more sensitive both to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions.

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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. PMID: 24601948

Via a systematic literature review, the authors concluded 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.

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Reynolds GK, Lewis DP, Richardson AM, Lidbury BA. Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort. J Intern Med. 2014 Apr;275(4):409-17. PMID: 24206536

In an Australian sample of CFS patients, 11% also suffered from POTS. CFS-POTS patients were significantly younger, had a shorter length of illness, experienced greater task difficulty and were able to stand for significantly shorter periods compared to the CFS-only patients. CFS-POTS patients experienced significantly lower baseline diastolic blood pressure, significantly higher heart rate and lower pulse pressures at each standing measurement. Early heart rate changes and overall heart rate change  were significant predictors of completion status, whereas heart rate variability  and female gender were significant predictors of increased perceived task difficulty.

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Nijs J, Ickmans K. Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning. J Intern Med. 2013 May;273(5):498-500. PMID: 23331489

Postural orthostatic tachycardia syndrome and its relationship to CFS is discussed.

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Lewis I, Pairman J, Spickett G, Newton JL. Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. J Intern Med. 2013 May;273(5):501-10. PMID: 23206180

CFS patients with POTS (13% of this sample) were younger, less fatigued, less depressed and had reduced daytime hypersomnolence, compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance and autonomic dysfunction.

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Chirilă EL, Postolache P. Orthostatic intolerance and chronic fatigue syndrome–possible related conditions. Rev Med Chir Soc Med Nat Iasi. 2013 Apr-Jun;117(2):388-93. PMID: 24340521

Many patients with chronic fatigue syndrome also had some form of orthostatic intolerance. Some studies suggested that dysautonomia may be the common problem in patients with these syndromes.

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Okamoto LE, Raj SR, Peltier A, Gamboa A, Shibao C, Diedrich A, Black BK, Robertson D, Biaggioni I. Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes. Clin Sci (Lond). 2012 Feb 1;122(4):183-92. PMID: 21906029

The authors compared CFS and POTS (postural tachycardia syndrome) patients, concluding that most POTS patients met the criteria for CFS. CFS-POTS patients have higher markers of sympathetic activation, but are part of the spectrum of POTS. Targeting this sympathetic activation should be considered in the treatment of these patients.

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Benarroch EE. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. Mayo Clin Proc. 2012 Dec;87(12):1214-25. PMID: 23122672

This paper provides a literature review on postural tachycardia syndrome (POTS), including its role in CFS.

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Allen J, Murray A, Di Maria C, Newton JL. Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker. Physiol Meas. 2012 Feb;33(2):231-41. PMID: 22273713

The researchers explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing.

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Ocon AJ, Messer Z, Medow M, Stewart J. Increasing orthostatic stress impairs neurocognitive functioning in Chronic Fatigue Syndrome with Postural Tachycardia Syndrome. Clin Sci (Lond). 2011 Sep 15. PMID: 21919887

Increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy, and information processing in CFS/postural orthostatic tachycardia syndrome, but this is not related to changes in cerebral blood flow velocity. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

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Jones DE, Gray J, Frith J, Newton JL. Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study. J Intern Med. 2011 Feb;269(2):182-8. PMID: 21073560

In CFS patients, intolerance is correlated with fatigue, and fatigue is worse in mornings than later in the day.

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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. PMID: 20890710

CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress.

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Costigan A, Elliott C, McDonald C, Newton JL. Orthostatic symptoms predict functional capacity in chronic fatigue syndrome: implications for management. QJM. 2010 Jun 9. PMID: 20534655

Treatment of orthostatic symptoms in CFS has the potential to improve functional capacity and quality of life.

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Hollingsworth KG, Jones DE, Taylor R, Blamire AM, Newton JL. Eur J Clin Invest. Impaired cardiovascular response to standing in Chronic Fatigue Syndrome. 2010 May 20. PMID: 20497461

Heart problems in CFS cause orthostatic intolerance, meaning that symptoms get worse when standing up.

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Wyller VB, Barbieri R, Thaulow E, Saul JP. Enhanced vagal withdrawal during mild orthostatic stress in adolescents with chronic fatigue. Ann Noninvasive Electrocardiol. 2008 Jan;13(1):67-73. PMID: 18234008

CFS patients have heart problems, emerging during mild orthostatic stress.  Possible underlying mechanisms include low blood volume and abnormalities of reflex mechanisms.

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Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Dec;101(12):961-5.  PMID: 18805903

Postural orthostatic tachycardia syndrome (POTS), with abnormally high heart rate on standing, is a frequent finding in patients with CFS/ME and results in fatigue.

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Galland BC, Jackson PM, Sayers RM, Taylor BJ. A matched case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome. Pediatr Res. 2008 Feb;63(2):196-202. PMID: 18091356

CFS patients were more susceptible to orthostatic intolerance, with the unique manifestation of postural orthostatic tachychardia syndrome.

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Wyller VB, Saul JP, Walløe L, Thaulow E. Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. Eur J Appl Physiol. 2008 Apr;102(6):623-32. PMID: 18066580

Adolescents with CFS have increased sympathetic activity at rest with exaggerated cardiovascular response to orthostatic stress, but attenuated cardiovascular response when performing isometric exercise during orthostatic stress.

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Agarwal AK, Garg R, Ritch A, Sarkar P. Postural orthostatic tachycardia syndrome. Postgrad Med J. 2007 Jul;83(981):478-80. PMID: 17621618

The clinical picture, diagnosis, and management of POTS are discussed.

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Wyller VB, Saul JP, Amlie JP, Thaulow E. Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue. Clin Physiol Funct Imaging. 2007 Jul;27(4):231-8. PMID: 17564672

Adolescents with CFS have sympathetic predominance of cardiovascular regulation during very mild orthostatic stress.

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Tanaka H. Autonomic function and child chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1105-12. PMID: 17561705

Autonomic function might be partly involved in CFS such as orthostatic dysfunction, but its priority in causing CFS is unclear.

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Natelson BH, Intriligator R, Cherniack NS, Chandler HK, Stewart JM. Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome. Dyn Med. 2007 Jan 30;6:2. PMID: 17263876

A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia.

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Naschitz JE, Yeshurun D, Rosner I. Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications. Med Hypotheses. 2004;62(2):203-6. PMID: 14962627

The authors hypothesize that dysautonomia is pivotal in the pathophysiology CFS and that manipulating the autonomic nervous system may be an effective treatment.

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Peckerman A, LaManca JJ, Qureishi B, Dahl KA, Golfetti R, Yamamoto Y, Natelson BH. Baroreceptor reflex and integrative stress responses in chronic fatigue syndrome. Psychosom Med. 2003 Sep-Oct;65(5):889-95. PMID: 14508037

In CFS, deficiencies in orthostatic regulation, but not in centrally mediated stress responses, may involve the baroreceptor reflex.

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Khan F, Spence V, Kennedy G, Belch JJ. Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome. Clin Physiol Funct Imaging. 2003 Sep;23(5):282-5. PMID: 12950326

Prolongation of acetylcholine-induced vasodilatation is suggestive of a disturbance to cholinergic pathways, perhaps within the vascular endothelium of patients with CFS, and might be related to some of the unusual vascular symptoms, such as hypotension and orthostatic intolerance, which are characteristic of the condition.

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Tanaka H, Matsushima R, Tamai H, Kajimoto Y. Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance. J Pediatr. 2002 Apr;140(4):412-7. PMID: 12006954

In a study of CFS patients, orthostatic intolerance determined by cardiovascular responses to standing was observed in 16 of 28 patients: instantaneous orthostatic hypotension in 8, delayed orthostatic hypotension in 2, and postural orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared spectroscopy at the onset of active standing was not found in 15 of 16 patients with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with chronic fatigue without orthostatic intolerance but only in 2 of 20 control subjects. Thirteen of 16 patients with orthostatic intolerance showed prolonged reduction in oxy-Hb during standing.

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Naschitz JE, Sabo E, Naschitz S, Shaviv N, Rosner I, Rozenbaum M, Gaitini L, Ahdoot A, Ahdoot M, Priselac RM, Eldar S, Zukerman E, Yeshurun D. Hemodynamic instability in chronic fatigue syndrome: indices and diagnostic significance. Semin Arthritis Rheum. 2001 Dec;31(3):199-208. PMID: 11740800

The hemodynamic instability score, related to cardiovascular response to postural challenge, adds objective criteria confirming the diagnosis of CFS.

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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 Aug;48(2):218-26. PMID: 10926298

Heart rate and blood pressure regulation in POTS and CFS patients are similar and indicate attenuated efferent vagal baroreflex associated with increased vasomotor tone. Loss of beat-to-beat heart rate control may contribute to a destabilized blood pressure resulting in orthostatic intolerance.

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Streeten DH, Thomas D, Bell DS. The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome. Am J Med Sci. 2000 Jul;320(1):1-8.  PMID: 10910366

Delayed orthostatic hypotension and/or tachycardia caused by excessive gravitational venous pooling, which is correctable with external lower-body compression, together with subnormal circulating erythrocyte volume, are very frequent, although not invariably demonstrable, findings in moderate to severe CFS.

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Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, Geraghty MT. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. J Pediatr. 1999 Oct;135(4):494-9. PMID: 10518084

Among patients with CFS and orthostatic intolerance, a subset also has Ehlers-Danlos syndrome.

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Stewart JM, Gewitz MH, Weldon A, Munoz J. Patterns of orthostatic intolerance: the orthostatic tachycardia syndrome and adolescent chronic fatigue. J Pediatr. 1999 Aug;135(2 Pt 1):218-25. PMID: 10431117

Symptoms and patterns of orthostatic heart rate and blood pressure change in orthostatic tachycardia syndrome overlap strongly with those of CFS. Orthostatic intolerance in orthostatic tachycardia syndrome may represent an attenuated form of chronic fatigue pathophysiology.

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Schondorf R, Benoit J, Wein T, Phaneuf D. Orthostatic intolerance in the chronic fatigue syndrome.J Auton Nerv Syst. 1999 Feb 15;75(2-3):192-201. PMID: 10189122

On average, the duration of disease and patient age were significantly less and the onset of symptoms was more often subacute in CFS patients with OI than in those without OI.

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Stewart JM, Gewitz MH, Weldon A, Arlievsky N, Li K, Munoz J. Orthostatic intolerance in adolescent chronic fatigue syndrome. Pediatrics. 1999 Jan;103(1):116-21. PMID: 9917448

CFS is highly related to orthostatic intolerance in adolescents. The orthostatic intolerance of CFS often has heart rate and BP responses similar to responses in the syndrome of orthostatic tachycardia, suggesting that a partial autonomic defect may contribute to symptomatology in these patients.

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Streeten DH, Anderson GH Jr. The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res. 1998 Apr;8(2):119-24. PMID: 9613802

Fatigue is a very common symptom in patients with delayed orthostatic hypotension, as well as both primary and secondary hypocortisolism.

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Rowe PC, Calkins H. Neurally mediated hypotension and chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):15S-21S. PMID: 9790477

Patients with CFS have a high prevalence of neurally mediated hypotension, and open treatment of this autonomic dysfunction has been associated with improvements in CFS symptoms.

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Rowe PC, Bou-Holaigah I, Kan JS, Calkins H. Is neurally mediated hypotension an unrecognised cause of chronic fatigue? Lancet. 1995 Mar 11;345(8950):623-4. PMID: 7898182

This study suggests an overlap in the symptoms of chronic fatigue syndrome and neurally mediated hypotension.

 

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