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Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review

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Abstract

Gastrointestinal symptoms are among the most common complaints in patients with postural tachycardia syndrome (POTS). In some cases, they dominate the clinical presentation and cause substantial disabilities, including significant weight loss and malnutrition, that require the use of invasive treatment to support caloric intake. Multiple cross-sectional studies have reported a high prevalence of gastrointestinal symptoms in POTS patients with connective tissue diseases, such as Ehlers–Danlos, hypermobile type, and in patients with evidence of autonomic neuropathy. Previous studies that evaluated gastric motility in these patients reported a wide range of abnormalities, particularly delayed gastric emptying. The pathophysiology of gastrointestinal symptoms in POTS is likely multifactorial and probably depends on the co-morbid conditions. In patients with POTS and Ehlers–Danlos syndromes, structural and functional abnormalities in the gastrointestinal connective tissue may play a significant role, whereas in neuropathic POTS, the gastrointestinal tract motility and gut hormonal secretion may be directly impaired due to localized autonomic denervation. In patients with normal gastrointestinal motility but persistent gastrointestinal symptoms, gastrointestinal functional disorders should be considered. We performed a systematic review of the literature related to POTS and gastrointestinal symptoms have proposed possible mechanisms and discussed diagnosis and treatment approaches for delayed gastric emptying, the most common gastrointestinal abnormality reported in patients with POTS.

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References

  1. Abell T, McCallum R, Hocking M, Koch K, Abrahamsson H, Leblanc I, Lindberg G, Konturek J, Nowak T, Quigley EMM, Tougas G, Starkebaum W (2003) Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology 125:421–428

    Article  PubMed  Google Scholar 

  2. Abell TL, Camilleri M, Donohoe K, Hasler WL, Lin HC, Maurer AH, McCallum RW, Nowak T, Nusynowitz ML, Parkman HP, Shreve P, Szarka LA, Snape WJ, Ziessman HA, Medicine ANaMSatSoN (2008) Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. Am J Gastroenterol 103:753–763

    Article  PubMed  Google Scholar 

  3. Abell TL, Van Cutsem E, Abrahamsson H, Huizinga JD, Konturek JW, Galmiche JP, VoelIer G, Filez L, Everts B, Waterfall WE, Domschke W, Bruley des Varannes S, Familoni BO, Bourgeois IM, Janssens J, Tougas G (2002) Gastric electrical stimulation in intractable symptomatic gastroparesis. Digestion 66:204–212

    Article  PubMed  Google Scholar 

  4. Al-Shekhlee A, Lindenberg JR, Hachwi RN, Chelimsky TC (2005) The value of autonomic testing in postural tachycardia syndrome. Clin Auton Res 15:219–222

    Article  PubMed  Google Scholar 

  5. Antiel RM, Risma JM, Grothe RM, Brands CK, Fischer PR (2008) Orthostatic intolerance and gastrointestinal motility in adolescents with nausea and abdominal pain. J Pediatr Gastroenterol Nutr 46:285–288

    Article  PubMed  Google Scholar 

  6. Arts J, Holvoet L, Caenepeel P, Bisschops R, Sifrim D, Verbeke K, Janssens J, Tack J (2007) Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis. Aliment Pharmacol Ther 26:1251–1258

    Article  PubMed  CAS  Google Scholar 

  7. Avetisyan M, Schill EM, Heuckeroth RO (2015) Building a second brain in the bowel. J Clin Investig 125:899–907

    Article  PubMed  Google Scholar 

  8. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ (1998) Ehlers–Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers–Danlos National Foundation (USA) and Ehlers–Danlos Support Group (UK). Am J Med Genet 77:31–37

    Article  PubMed  CAS  Google Scholar 

  9. Benarroch EE (2012) Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. Mayo Clin Proc 87:1214–1225

    Article  PubMed  PubMed Central  Google Scholar 

  10. Bradley SE, Childs AW, Combes B, Cournand A, Wade OL, Wheeler HO (1956) The effect of exercise on the splanchnic blood flow and splanchnic blood volume in normal man. Clin Sci 15:457–463

    PubMed  CAS  Google Scholar 

  11. Browning KN, Travagli RA (2014) Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol 4:1339–1368

    Article  PubMed  PubMed Central  Google Scholar 

  12. Caio G, De Giorgio R, Venturi A, Giancola F, Latorre R, Boschetti E, Serra M, Ruggeri E, Volta U (2015) Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations. Gastroenterol Hepatol Bed Bench 8:146–152

    PubMed  PubMed Central  Google Scholar 

  13. Castori M, Morlino S, Celletti C, Celli M, Morrone A, Colombi M, Camerota F, Grammatico P (2012) Management of pain and fatigue in the joint hypermobility syndrome (a.k.a. Ehlers–Danlos syndrome, hypermobility type): principles and proposal for a multidisciplinary approach. Am J Med Genet Part A 158A:2055–2070

    Article  PubMed  Google Scholar 

  14. Catassi C, Rätsch IM, Fabiani E, Rossini M, Bordicchia F, Candela F, Coppa GV, Giorgi PL (1994) Coeliac disease in the year 2000: exploring the iceberg. Lancet (London, England) 343:200–203

    Article  CAS  Google Scholar 

  15. Chaudhuri KR, Thomaides T, Mathias CJ (1992) Abnormality of superior mesenteric artery blood flow responses in human sympathetic failure. J Physiol 457:477–489

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Cherian D, Parkman HP (2012) Nausea and vomiting in diabetic and idiopathic gastroparesis. Neurogastroenterol Motil 24(217–222):e103

    Google Scholar 

  17. Chin RL, Sander HW, Brannagan TH, Green PHR, Hays AP, Alaedini A, Latov N (2003) Celiac neuropathy. Neurology 60:1581–1585

    Article  PubMed  CAS  Google Scholar 

  18. De Wandele I, Rombaut L, Malfait F, De Backer T, De Paepe A, Calders P (2013) Clinical heterogeneity in patients with the hypermobility type of Ehlers–Danlos syndrome. Res Dev Disabil 34:873–881

    Article  PubMed  Google Scholar 

  19. Fikree A, Aziz Q, Sifrim D (2017) Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome. Neurogastroenterol Motil 29(6). doi:https://doi.org/10.1111/nmo.13029

  20. Fikree A, Chelimsky G, Collins H, Kovacic K, Aziz Q (2017) Gastrointestinal involvement in the Ehlers–Danlos syndromes. Am J Med Genet Part C Semin Med Genet 175:181–187

    Article  PubMed  Google Scholar 

  21. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG (2011) Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 21:69–72

    Article  PubMed  Google Scholar 

  22. Friedenberg FK, Palit A, Parkman HP, Hanlon A, Nelson DB (2008) Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol 103:416–423

    Article  PubMed  CAS  Google Scholar 

  23. Fujimura J, Camilleri M, Low PA, Novak V, Novak P, Opfer-Gehrking TL (1997) Effect of perturbations and a meal on superior mesenteric artery flow in patients with orthostatic hypotension. J Auton Nerv Syst 67:15–23

    Article  PubMed  CAS  Google Scholar 

  24. Gazit Y, Nahir AM, Grahame R, Jacob G (2003) Dysautonomia in the joint hypermobility syndrome. Am J Med 115:33–40

    Article  PubMed  Google Scholar 

  25. Gibbons CH, Bonyhay I, Benson A, Wang N, Freeman R (2013) Structural and functional small fiber abnormalities in the neuropathic postural tachycardia syndrome. PLoS ONE 8:e84716

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Gibbons CH, Freeman R (2005) Autonomic neuropathy and coeliac disease. J Neurol Neurosurg Psychiatry 76:579–581

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Hadjivassiliou M, Grünewald RA, GaB Davies-Jones (2002) Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 72:560–563

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Hasler WL, Wilson LA, Parkman HP, Koch KL, Abell TL, Nguyen L, Pasricha PJ, Snape WJ, McCallum RW, Sarosiek I, Farrugia G, Calles J, Lee L, Tonascia J, Unalp-Arida A, Hamilton F (2013) Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting. Neurogastroenterol Motil 25(427–438):e300–301

    Google Scholar 

  29. Hibbard ML, Dunst CM, Swanström LL (2011) Laparoscopic and endoscopic pyloroplasty for gastroparesis results in sustained symptom improvement. J Gastrointest Surg 15:1513–1519

    Article  PubMed  Google Scholar 

  30. Holmes GM (2012) Upper gastrointestinal dysmotility after spinal cord injury: is diminished vagal sensory processing one culprit? Front Physiol 3:277. doi:https://doi.org/10.3389/fphys.2012.00277

  31. Jacob G, Costa F, Shannon JR, Robertson RM, Wathen M, Stein M, Biaggioni I, Ertl A, Black B, Robertson D (2000) The neuropathic postural tachycardia syndrome. N Engl J Med 343:1008–1014

    Article  PubMed  CAS  Google Scholar 

  32. Jacob G, Robertson D, Mosqueda-Garcia R, Ertl AC, Robertson RM, Biaggioni I (1997) Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system. Am J Med 103:128–133

    Article  PubMed  CAS  Google Scholar 

  33. Johnston SD, Watson RG, McMillan SA, Sloan J, Love AH (1997) Prevalence of coeliac disease in Northern Ireland. Lancet (London, England) 350:1370

    Article  CAS  Google Scholar 

  34. Joyner MJ, Masuki S (2008) POTS versus deconditioning: the same or different? Clin Auton Res 18:300–307

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lacy BE, Crowell MD, Schettler-Duncan A, Mathis C, Pasricha PJ (2004) The treatment of diabetic gastroparesis with botulinum toxin injection of the pylorus. Diabetes Care 27:2341–2347

    Article  PubMed  CAS  Google Scholar 

  36. Lawal A, Barboi A, Krasnow A, Hellman R, Jaradeh S, Massey BT (2007) Rapid gastric emptying is more common than gastroparesis in patients with autonomic dysfunction. Am J Gastroenterol 102:618–623

    Article  PubMed  Google Scholar 

  37. Li H, Yu X, Liles C, Khan M, Vanderlinde-Wood M, Galloway A, Zillner C, Benbrook A, Reim S, Collier D, Hill MA, Raj SR, Okamoto LE, Cunningham MW, Aston CE, Kem DC (2014) Autoimmune basis for postural tachycardia syndrome. J Am Heart Assoc 3:e000755

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6:e1000100

    Article  PubMed  PubMed Central  Google Scholar 

  39. Loavenbruck A, Iturrino J, Singer W, Sletten DM, Low PA, Zinsmeister AR, Bharucha AE (2015) Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome. Neurogastroenterol Motil 27:92–98

    Article  PubMed  CAS  Google Scholar 

  40. Lomax AE, Sharkey KA, Furness JB (2010) The participation of the sympathetic innervation of the gastrointestinal tract in disease states. Neurogastroenterol Motil 22:7–18

    PubMed  CAS  Google Scholar 

  41. Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, De Backer J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B (2017) The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet Part C Semin Med Genet 175:8–26

    Article  PubMed  Google Scholar 

  42. Mauro A, Orsi L, Mortara P, Costa P, Schiffer D (1991) Cerebellar syndrome in adult celiac disease with vitamin E deficiency. Acta Neurol Scand 84:167–170

    Article  PubMed  CAS  Google Scholar 

  43. McCallum RW, Snape W, Brody F, Wo J, Parkman HP, Nowak T (2010) Gastric electrical stimulation with Enterra therapy improves symptoms from diabetic gastroparesis in a prospective study. Clin Gastroenterol Hepatol 8:947–954 (quiz e116)

    Article  PubMed  Google Scholar 

  44. Moore JG, Christian PE, Brown JA, Brophy C, Datz F, Taylor A, Alazraki N (1984) Influence of meal weight and caloric content on gastric emptying of meals in man. Dig Dis Sci 29:513–519

    Article  PubMed  CAS  Google Scholar 

  45. Moore JG, Christian PE, Coleman RE (1981) Gastric emptying of varying meal weight and composition in man. Evaluation by dual liquid- and solid-phase isotopic method. Dig Dis Sci 26:16–22

    Article  PubMed  CAS  Google Scholar 

  46. Mustafa HI, Garland EM, Biaggioni I, Black BK, Dupont WD, Robertson D, Raj SR (2011) Abnormalities of angiotensin regulation in postural tachycardia syndrome. Heart Rhythm 8:422–428

    Article  PubMed  PubMed Central  Google Scholar 

  47. Nelson AD, Mouchli MA, Valentin N, Deyle D, Pichurin P, Acosta A, Camilleri M (2015) Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic. Neurogastroenterol Motil 27:1657–1666

    Article  PubMed  CAS  Google Scholar 

  48. Park K-J, Singer W, Sletten DM, Low PA, Bharucha AE (2013) Gastric emptying in postural tachycardia syndrome: a preliminary report. Clin Auton Res 23:163–167

    Article  PubMed  PubMed Central  Google Scholar 

  49. Parkman HP, Van Natta ML, Abell TL, McCallum RW, Sarosiek I, Nguyen L, Snape WJ, Koch KL, Hasler WL, Farrugia G, Lee L, Unalp-Arida A, Tonascia J, Hamilton F, Pasricha PJ (2013) Effect of nortriptyline on symptoms of idiopathic gastroparesis: the NORIG randomized clinical trial. JAMA 310:2640–2649

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Pederson CL, Brook JB (2017) Health-related quality of life and suicide risk in postural tachycardia syndrome. Clin Auton Res 27:75–81

    Article  PubMed  Google Scholar 

  51. Penny HA, Aziz I, Ferrar M, Atkinson J, Hoggard N, Hadjivassiliou M, West JN, Sanders DS (2016) Is there a relationship between gluten sensitivity and postural tachycardia syndrome? Eur J Gastroenterol Hepatol 28:1383–1387

    Article  PubMed  CAS  Google Scholar 

  52. Perkel MS, Moore C, Hersh T, Davidson ED (1979) Metoclopramide therapy in patients with delayed gastric emptying: a randomized, double-blind study. Dig Dis Sci 24:662–666

    Article  PubMed  CAS  Google Scholar 

  53. Raj SR (2006) The postural tachycardia syndrome (POTS): pathophysiology, diagnosis & management. Indian Pacing Electrophysiol J 6:84–99

    PubMed  PubMed Central  Google Scholar 

  54. Raj SR, Robertson D (2007) Blood volume perturbations in the postural tachycardia syndrome. Am J Med Sci 334:57–60

    Article  PubMed  Google Scholar 

  55. Raj SR, Stiles L, Shaw B, Green EA, Dorminy CA, Shibao CA, Okamoto LE, Garland E, Diedrich A, Biaggioni I, Robertson D (2016) The diagnostic experience in postural tachycardia syndrome: insights from a cross-sectional community-based survey. In: 27th International Symp on the Autonomic Nervous System. Clin Auton Res 26:356

  56. Rao AS, Camilleri M (2010) Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther 31:11–19

    Article  PubMed  CAS  Google Scholar 

  57. Sarosiek I, Forster J, Lin Z, Cherry S, Sarosiek J, McCallum R (2013) The addition of pyloroplasty as a new surgical approach to enhance effectiveness of gastric electrical stimulation therapy in patients with gastroparesis. Neurogastroenterol Motil 25:134–e180

    Article  PubMed  CAS  Google Scholar 

  58. Seligman WH, Low DA, Asahina M, Mathias CJ (2013) Abnormal gastric myoelectrical activity in postural tachycardia syndrome. Clin Auton Res 23:73–80

    Article  PubMed  Google Scholar 

  59. Shill HA, Alaedini A, Bushara KO, Latov N, Hallett M (2003) Anti-ganglioside antibodies in idiopathic and hereditary cerebellar degeneration. Neurology 60:1672–1673

    Article  PubMed  Google Scholar 

  60. Smith HS, Cox LR, Smith BR (2012) Dopamine receptor antagonists. Ann Palliat Med 1:137–142

    PubMed  Google Scholar 

  61. Sugumar A, Singh A, Pasricha PJ (2008) A systematic review of the efficacy of domperidone for the treatment of diabetic gastroparesis. Clin Gastroenterol Hepatol 6:726–733

    Article  PubMed  Google Scholar 

  62. Takala J (1996) Determinants of splanchnic blood flow. Br J Anaesth 77:50–58

    Article  PubMed  CAS  Google Scholar 

  63. Talley NJ (2003) Diabetic gastropathy and prokinetics. Am J Gastroenterol 98:264–271

    Article  PubMed  Google Scholar 

  64. Tani H, Singer W, McPhee BR, Opfer-Gehrking TL, Haruma K, Kajiyama G, Low PA (2000) Splanchnic-mesenteric capacitance bed in the postural tachycardia syndrome (POTS). Auton Neurosci Basic Clin 86:107–113

    Article  CAS  Google Scholar 

  65. Toro JP, Lytle NW, Patel AD, Davis SS, Christie JA, Waring JP, Sweeney JF, Lin E (2014) Efficacy of laparoscopic pyloroplasty for the treatment of gastroparesis. J Am Coll Surg 218:652–660

    Article  PubMed  Google Scholar 

  66. Tursi A, Giorgetti GM, Iani C, Arciprete F, Brandimarte G, Capria A, Fontana L (2006) Peripheral neurological disturbances, autonomic dysfunction, and antineuronal antibodies in adult celiac disease before and after a gluten-free diet. Dig Dis Sci 51:1869–1874

    Article  PubMed  Google Scholar 

  67. Wang LB, Culbertson CJ, Deb A, Morgenshtern K, Huang H, Hohler AD (2015) Gastrointestinal dysfunction in postural tachycardia syndrome. J Neurol Sci 359:193–196

    Article  PubMed  Google Scholar 

  68. Zarate N, Farmer AD, Grahame R, Mohammed SD, Knowles CH, Scott SM, Aziz Q (2010) Unexplained gastrointestinal symptoms and joint hypermobility: is connective tissue the missing link? Neurogastroenterol Motil 22:252–e278

    Article  PubMed  CAS  Google Scholar 

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Funding

S.E.M. is supported by Grant NIH 5T32GM007569, and C.A.S. was supported by Doris Duke Foundation Career Development Award. The study was supported by Vanderbilt CTSA, NACTS/NIH Grant 1UL1 RR000445, and NINDS/NIH U54NS065736.

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  1. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 506 RRB, 2222 Pierce Ave, Nashville, TN, 37232, USA

    Shahram E. Mehr & Cyndya A. Shibao

  2. Department of Surgery, Vanderbilt University Medical Center, Nashville, USA

    Adrian Barbul

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Correspondence to Cyndya A. Shibao.

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C.A.S. is a consultant for Lundbeck Pharmaceuticals. S.E.M. and A.B. declare that they have no conflicts of interest.

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Mehr, S.E., Barbul, A. & Shibao, C.A. Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review. Clin Auton Res 28, 411–421 (2018). https://doi.org/10.1007/s10286-018-0519-x

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