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Semin Neurol 2023; 43(04): 540-552
DOI: 10.1055/s-0043-1771469
Review Article

Gastroparesis and Gastroparesis Syndromes as Neuromuscular Disorders

Le Yu Naing
1   Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky
,
Prateek Mathur
1   Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky
,
Garvit Chhabra
1   Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky
,
Abigail Stocker
1   Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky
,
Thomas L. Abell
1   Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky
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Abstract

Gastroparesis syndromes (GpS) are a spectrum of disorders presenting with characteristic symptoms increasingly recognized as being gastrointestinal (GI) neuromuscular disorders (NMDs). This review focuses on GpS as a manifestation of neurologic disorders of GI NMD. GpS can be associated with systemic abnormalities, including inflammatory, metabolic, and serologic disorders, as well as autoimmune antibodies via nerve and muscle targets in the GI tract, which can be treated with immunotherapy, such as intravenous immunoglobulin. GpS are associated with autonomic (ANS) and enteric (ENS) dysfunction. Disorders of ANS may interact with the ENS and are the subject of continued investigation. ENS disorders have been recognized for a century but have only recently begun to be fully quantified. Anatomic structural changes in the GI tract are increasingly recognized in GpS. Detailed descriptions of anatomic changes in GpS, and their correlation with physiologic findings, have opened a new era of investigation. The management of GpS, when viewed as GI NMD, has shifted the paradigms of both diagnosis and treatment. This article concludes with current approaches to GpS directed at underlying neuromuscular pathology.

Keywords

gastroparesis syndromes - neuromuscular disorders - motility - anatomic nervous system - enteric nervous system


Publication History

Article published online:
10 August 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Abell TL, Kedar A, Stocker A. et al. Pathophysiology of gastroparesis syndromes includes anatomic and physiologic abnormalities. Dig Dis Sci 2021; 66 (04) 1127-1141
    CrossrefPubMedGoogle Scholar
  • 2 Pasricha PJ, Grover M, Yates KP. et al; National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health Gastroparesis Clinical Research Consortium. Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features. Gastroenterology 2021; 160 (06) 2006-2017
    CrossrefPubMedGoogle Scholar
  • 3 Camilleri M, Kuo B, Nguyen L. et al. ACG clinical guideline: gastroparesis. Am J Gastroenterol 2022; 117 (08) 1197-1220
    CrossrefPubMedGoogle Scholar
  • 4 Mathur P, Abell TL. . Management of Gastroparesis in 2022 GI and Hepatology News 2022 . Available at: https://www.mdedge.com/gihepnews/article/254039/ibd-intestinal-disorders/management-gastroparesis-2022
    PubMed
  • 5 Siraj ES, Homko C, Wilson LA. et al. Islet cell associated autoantibodies and C-peptide levels in patients with diabetes and symptoms of gastroparesis. Front Endocrinol (Lausanne) 2018; 9: 32
    CrossrefPubMedGoogle Scholar
  • 6 Dhamija R, Tan KM, Pittock SJ, Foxx-Orenstein A, Benarroch E, Lennon VA. Serologic profiles aiding the diagnosis of autoimmune gastrointestinal dysmotility. Clin Gastroenterol Hepatol 2008; 6 (09) 988-992
    CrossrefPubMedGoogle Scholar
  • 7 Andrews PLR. Nausea, vomiting, and the autonomic nervous system. In: Mathias CJ, Bannister SR. eds. Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System: Oxford University Press; 2013
    CrossrefGoogle Scholar
  • 8 Pasricha PJ, Mehta KR, May KP. et al. Characterization of the inflammatory response in idiopathic gastroparesis reveals a role for macrophage derived factors. Gastroenterology 2011; 5: S-709
    CrossrefPubMedGoogle Scholar
  • 9 Baig MA, Randhawa T, Majeed MB, Agrawal R, Gandhi SR. Occult non-small cell lung cancer presenting as paraneoplastic gastroparesis: a case report and literature review. Cureus 2019; 11 (03) e4216
    PubMedGoogle Scholar
  • 10 Kashyap P, Farrugia G. Enteric autoantibodies and gut motility disorders. Gastroenterol Clin North Am 2008; 37 (02) 397-410 , vi–vii
    CrossrefPubMedGoogle Scholar
  • 11 Parkman HP, Van Natta ML, Makol A. et al; NIDDK Gastroparesis Clinical Research Consortium. Prevalence and clinical correlates of antinuclear antibody in patients with gastroparesis. Neurogastroenterol Motil 2022; 34 (05) e14270
    CrossrefPubMedGoogle Scholar
  • 12 Nakane S, Umeda M, Kawashiri SY. et al. Detecting gastrointestinal manifestations in patients with systemic sclerosis using anti-gAChR antibodies. Arthritis Res Ther 2020; 22 (01) 32
    CrossrefPubMedGoogle Scholar
  • 13 Fujikawa Y, Tominaga K. Neuro-gastroenterology: enteric nervous system. In: Tominaga K. ed. Functional Dyspepsia: Evidences in Pathophysiology and Treatment. Singapore: Springer Nature; 2018: 51-58
    Google Scholar
  • 14 Nakane S, Mukaino A, Ihara E, Ogawa Y. Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology. Immunol Med 2021; 44 (02) 74-85
    CrossrefPubMedGoogle Scholar
  • 15 Gyger G, Baron M. Systemic sclerosis: gastrointestinal disease and its management. Rheum Dis Clin North Am 2015; 41 (03) 459-473
    CrossrefPubMedGoogle Scholar
  • 16 Gala K, Stocker A, Tu Y. et al. Baseline characteristics and predictive factors of intravenous immunoglobulin response in drug and device refractory gastroparesis symptoms. J Clin Gastroenterol 2023; 57 (02) 172-177
    CrossrefPubMedGoogle Scholar
  • 17 Beyder A, Farrugia G. Targeting ion channels for the treatment of gastrointestinal motility disorders. Therap Adv Gastroenterol 2012; 5 (01) 5-21
    CrossrefPubMedGoogle Scholar
  • 18 Joshi V, Strege PR, Farrugia G, Beyder A. Mechanotransduction in gastrointestinal smooth muscle cells: role of mechanosensitive ion channels. Am J Physiol Gastrointest Liver Physiol 2021; 320 (05) G897-G906
    CrossrefPubMedGoogle Scholar
  • 19 Morimoto N, Takahashi S, Inaba T. et al. A case of seropositive autoimmune autonomic ganglionopathy with diffuse esophageal spasm. J Clin Neurosci 2017; 39: 90-92
    CrossrefPubMedGoogle Scholar
  • 20 Hubball AW, Lang B, Souza MA, Curran OD, Martin JE, Knowles CH. Voltage-gated potassium channel (K(v) 1) autoantibodies in patients with chagasic gut dysmotility and distribution of K(v) 1 channels in human enteric neuromusculature (autoantibodies in GI dysmotility). Neurogastroenterol Motil 2012; 24 (08) 719-728 , e344
    CrossrefPubMedGoogle Scholar
  • 21 Chhabra G, Mathur P, Mcelmurray L. et al. Sa1477: Role of intravenous immunoglobulin in treatment of drug refractory gastroparesis. Gastroenterology 2022; 162 (07) S-388-S-389
    CrossrefPubMedGoogle Scholar
  • 22 Camilleri M. Gastrointestinal motility disorders in neurologic disease. J Clin Invest 2021; 131 (04) 131
    CrossrefPubMedGoogle Scholar
  • 23 Liff JM, Labovitz D, Robbins MS. Profound gastroparesis after bilateral posterior inferior cerebellar artery territory infarcts. Clin Neurol Neurosurg 2012; 114 (06) 789-791
    CrossrefPubMedGoogle Scholar
  • 24 Khanna L, Zeydan B, Kantarci OH, Camilleri M. Gastrointestinal motility disorders in patients with multiple sclerosis: a single-center study. Neurogastroenterol Motil 2022; 34 (08) e14326
    CrossrefPubMedGoogle Scholar
  • 25 Reddymasu SC, Bonino J, McCallum RW. Gastroparesis secondary to a demyelinating disease: a case series. BMC Gastroenterol 2007; 7: 3
    CrossrefPubMedGoogle Scholar
  • 26 Hardoff R, Sula M, Tamir A. et al. Gastric emptying time and gastric motility in patients with Parkinson's disease. Mov Disord 2001; 16 (06) 1041-1047
    CrossrefPubMedGoogle Scholar
  • 27 Marie I, Gourcerol G, Leroi AM, Ménard JF, Levesque H, Ducrotté P. Delayed gastric emptying determined using the 13C-octanoic acid breath test in patients with systemic sclerosis. Arthritis Rheum 2012; 64 (07) 2346-2355
    CrossrefPubMedGoogle Scholar
  • 28 Nagaraja V, McMahan ZH, Getzug T, Khanna D. Management of gastrointestinal involvement in scleroderma. Curr Treatm Opt Rheumatol 2015; 1 (01) 82-105
    CrossrefPubMedGoogle Scholar
  • 29 Kuo B, Singh P. Nausea and vomiting related to the central nervous system diseases. In: Koch KL, Hasler WL. eds. Nausea and Vomiting: Diagnosis and Treatment. Cham: Springer International Publishing; 2017: 109-118
    Google Scholar
  • 30 Hoscheit M, Kamal A, Cline M. Gastroparesis in a patient with gastric AL amyloidosis. Case Rep Gastroenterol 2018; 12 (02) 317-321
    CrossrefPubMedGoogle Scholar
  • 31 Camilleri M, Lembo A, Katzka DA. Opioids in gastroenterology: treating adverse effects and creating therapeutic benefits. Clin Gastroenterol Hepatol 2017; 15 (09) 1338-1349
    CrossrefPubMedGoogle Scholar
  • 32 Little TJ, Pilichiewicz AN, Russo A. et al. Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses. J Clin Endocrinol Metab 2006; 91 (05) 1916-1923
    CrossrefPubMedGoogle Scholar
  • 33 Deane AM, Nguyen NQ, Stevens JE. et al. Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia. J Clin Endocrinol Metab 2010; 95 (01) 215-221
    CrossrefPubMedGoogle Scholar
  • 34 Aurora SK, Kori SH, Barrodale P, McDonald SA, Haseley D. Gastric stasis in migraine: more than just a paroxysmal abnormality during a migraine attack. Headache 2006; 46 (01) 57-63
    CrossrefPubMedGoogle Scholar
  • 35 Aurora S, Kori S, Barrodale P, Nelsen A, McDonald S. Gastric stasis occurs in spontaneous, visually induced, and interictal migraine. Headache 2007; 47 (10) 1443-1446
    CrossrefPubMedGoogle Scholar
  • 36 Yalcin H, Okuyucu EE, Ucar E, Duman T, Yilmazer S. Changes in liquid emptying in migraine patients: diagnosed with liquid phase gastric emptying scintigraphy. Intern Med J 2012; 42 (04) 455-459
    CrossrefPubMedGoogle Scholar
  • 37 Yu YH, Jo Y, Jung JY, Kim BK, Seok JW. Gastric emptying in migraine: a comparison with functional dyspepsia. J Neurogastroenterol Motil 2012; 18 (04) 412-418
    CrossrefPubMedGoogle Scholar
  • 38 Tokola RA, Neuvonen PJ. Effects of migraine attack and metoclopramide on the absorption of tolfenamic acid. Br J Clin Pharmacol 1984; 17 (01) 67-75
    CrossrefPubMedGoogle Scholar
  • 39 Kim J, Lee S, Rhew K. Association between gastrointestinal diseases and migraine. Int J Environ Res Public Health 2022; 19 (07) 19
    CrossrefPubMedGoogle Scholar
  • 40 Aurora SK, Shrewsbury SB, Ray S, Hindiyeh N, Nguyen L. A link between gastrointestinal disorders and migraine: insights into the gut-brain connection. Headache 2021; 61 (04) 576-589
    CrossrefPubMedGoogle Scholar
  • 41 Christensen CJ, Johnson WD, Abell TL. Patients with cyclic vomiting pattern and diabetic gastropathy have more migraines, abnormal electrogastrograms, and gastric emptying. Scand J Gastroenterol 2008; 43 (09) 1076-1081
    CrossrefPubMedGoogle Scholar
  • 42 Cámara-Lemarroy CR, Rodriguez-Gutierrez R, Monreal-Robles R, Marfil-Rivera A. Gastrointestinal disorders associated with migraine: a comprehensive review. World J Gastroenterol 2016; 22 (36) 8149-8160
    CrossrefPubMedGoogle Scholar
  • 43 Ailani J, Kaiser EA, Mathew PG. et al. Role of calcitonin gene-related peptide on the gastrointestinal symptoms of migraine-clinical considerations: a narrative review. Neurology 2022; 99 (19) 841-853
    CrossrefPubMedGoogle Scholar
  • 44 Parkman HP. Migraine and gastroparesis from a gastroenterologist's perspective. Headache 2013; 53 (Suppl. 01) 4-10
    CrossrefPubMedGoogle Scholar
  • 45 Aurora SK, Papapetropoulos S, Kori SH, Kedar A, Abell TL. Gastric stasis in migraineurs: etiology, characteristics, and clinical and therapeutic implications. Cephalalgia 2013; 33 (06) 408-415
    CrossrefPubMedGoogle Scholar
  • 46 Stocker A, Abell TL, Rashed H, Kedar A, Boatright B, Chen J. Autonomic evaluation of patients with gastroparesis and neurostimulation: comparisons of direct/systemic and indirect/cardiac measures. Gastroenterol Res 2016; 9 (01) 10-16
    CrossrefPubMedGoogle Scholar
  • 47 Abell TL, Parajouli D. Nausea and vomiting related to autonomic nervous system disorders. In: Koch K, Hasler W. eds. Nausea and Vomiting. Switzerland: Springer; 2017
    Google Scholar
  • 48 Nguyen L, Wilson LA, Miriel L. et al; NIDDK Gastroparesis Clinical Research Consortium (GpCRC). Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: relationship with etiology, gastric emptying, and symptom severity. Neurogastroenterol Motil 2020; 32 (08) e13810
    CrossrefPubMedGoogle Scholar
  • 49 Hassan H, Ganguli S, Rashed H, Johnson W, Bhandari B, Abell T. Autonomic and enteric function profiling can predict disordered gastric emptying in diabetic gastropathy. Med Biol Eng Comput 2021; 59 (02) 327-332
    CrossrefPubMedGoogle Scholar
  • 50 Abell T, Cardoso S, Schwartzbaum JA. et al. Diabetic gastroparesis is associated with an abnormality in sympathetic innervation. Eur J Gastroenterol Hepatol 1994; 6: 7
    CrossrefPubMedGoogle Scholar
  • 51 Asakawa H, Onishi M, Hayashi I, Fukuda A, Tokunaga K. Comparison between coefficient of R-R interval variation and gastric emptying in type 2 diabetes mellitus patients. J Gastroenterol Hepatol 2005; 20 (09) 1358-1364
    CrossrefPubMedGoogle Scholar
  • 52 Mohammad MK, Pepper DJ, Kedar A. et al. Measures of autonomic dysfunction in diabetic and idiopathic gastroparesis. Gastroenterol Res 2016; 9 (4-5): 65-69
    CrossrefPubMedGoogle Scholar
  • 53 Shine A, Mathur P, Ahmed S. et al. Low-resolution electrogastrogram at baseline and response to temporary gastric electrical stimulation - a comparison of cutaneous with mucosal recordings. Neuromodulation 2022; 25 (08) 1150-1159
    CrossrefPubMedGoogle Scholar
  • 54 Gharibans AA, Calder S, Varghese C. et al. Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a novel non-invasive gastric mapping device. medRxiv 2022; DOI: 10.1101/2022.02.07.22270514.
    CrossrefPubMedGoogle Scholar
  • 55 Varghese C, Schamberg G, Calder S. et al. Normative values for body surface gastric mapping evaluations of gastric motility using gastric alimetry: spectral analysis. Am J Gastroenterol 2023; 118 (06) 1047-1057
    CrossrefPubMedGoogle Scholar
  • 56 Abell TL, Kedar A, Stocker A. et al. Gastroparesis syndromes: response to electrical stimulation. Neurogastroenterol Motil 2019; 31 (03) e13534
    CrossrefPubMedGoogle Scholar
  • 57 Lawal A, Barboi A, Krasnow A, Hellman R, Jaradeh S, Massey BT. Rapid gastric emptying is more common than gastroparesis in patients with autonomic dysfunction. Am J Gastroenterol 2007; 102 (03) 618-623
    CrossrefPubMedGoogle Scholar
  • 58 Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation 2007; 115 (03) 387-397
    CrossrefPubMedGoogle Scholar
  • 59 Ziegler D, Zentai CP, Perz S. et al; KORA Study Group. Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population: the MONICA/KORA Augsburg Cohort Study. Diabetes Care 2008; 31 (03) 556-561
    CrossrefPubMedGoogle Scholar
  • 60 Tu Y, Abell TL, Raj SR, Mar PL. Mechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome. Neurogastroenterol Motil 2020; 32 (12) e14031
    CrossrefPubMedGoogle Scholar
  • 61 Tufvesson H, Hamrefors V, Roth B. et al. Sociodemographic factors, nutritional status, and inflammatory markers in patients with postural orthostatic tachycardia syndrome. Acta Neurol Scand 2023; 2023: 3992718
    CrossrefPubMedGoogle Scholar
  • 62 Zhou J, O'Connor MD, Ho V. The potential for gut organoid derived interstitial cells of Cajal in replacement therapy. Int J Mol Sci 2017; 18 (10) 2059
    CrossrefPubMedGoogle Scholar
  • 63 Iino S, Horiguchi K. Interstitial cells of Cajal are involved in neurotransmission in the gastrointestinal tract. Acta Histochem Cytochem 2006; 39 (06) 145-153
    CrossrefPubMedGoogle Scholar
  • 64 Harberson J, Thomas RM, Harbison SP, Parkman HP. Gastric neuromuscular pathology in gastroparesis: analysis of full-thickness antral biopsies. Dig Dis Sci 2010; 55 (02) 359-370
    CrossrefPubMedGoogle Scholar
  • 65 Lin Z, Sarosiek I, Forster J, Damjanov I, Hou Q, McCallum RW. Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis. Neurogastroenterol Motil 2010; 22 (01) 56-61 , e10
    CrossrefPubMedGoogle Scholar
  • 66 Park KS, Cho KB, Hwang IS. et al. Characterization of smooth muscle, enteric nerve, interstitial cells of Cajal, and fibroblast-like cells in the gastric musculature of patients with diabetes mellitus. World J Gastroenterol 2016; 22 (46) 10131-10139
    CrossrefPubMedGoogle Scholar
  • 67 Grover M, Bernard CE, Pasricha PJ. et al; NIDDK Gastroparesis Clinical Research Consortium (GpCRC). Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum. Neurogastroenterol Motil 2017; 29 (06) DOI: 10.1111/nmo.13018.
    CrossrefPubMedGoogle Scholar
  • 68 Huizinga JD, Thuneberg L, Klüppel M, Malysz J, Mikkelsen HB, Bernstein A. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 1995; 373 (6512): 347-349
    CrossrefPubMedGoogle Scholar
  • 69 Torihashi S, Nishi K, Tokutomi Y, Nishi T, Ward S, Sanders KM. Blockade of kit signaling induces transdifferentiation of interstitial cells of Cajal to a smooth muscle phenotype. Gastroenterology 1999; 117 (01) 140-148
    CrossrefPubMedGoogle Scholar
  • 70 Gottfried-Blackmore A, Namkoong H, Adler E. et al. Gastric mucosal immune profiling and dysregulation in idiopathic gastroparesis. Clin Transl Gastroenterol 2021; 12 (05) e00349
    CrossrefPubMedGoogle Scholar
  • 71 Pasricha PJ, Grover M, Yates KP. et al; NIDDK/NIH GpCRC Consortium. Progress in gastroparesis - a narrative review of the work of the Gastroparesis Clinical Research Consortium. Clin Gastroenterol Hepatol 2022; 20 (12) 2684-2695.e3
    CrossrefPubMedGoogle Scholar
  • 72 Grover M, Farrugia G, Lurken MS. et al; NIDDK Gastroparesis Clinical Research Consortium. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology 2011; 140 (05) 1575-85.e8
    CrossrefPubMedGoogle Scholar
  • 73 Lahr CJ, Griffith J, Subramony C. et al. Gastric electrical stimulation for abdominal pain in patients with symptoms of gastroparesis. Am Surg 2013; 79 (05) 457-464
    CrossrefPubMedGoogle Scholar
  • 74 Omer E, Kedar A, Nagarajarao HS. et al. Cajal cell counts are important predictors of outcomes in drug refractory gastroparesis patients with neurostimulation. J Clin Gastroenterol 2019; 53 (05) 366-372
    CrossrefPubMedGoogle Scholar
  • 75 Heckroth M, Luckett RT, Moser C, Parajuli D, Abell TL. Nausea and vomiting in 2021: a comprehensive update. J Clin Gastroenterol 2021; 55 (04) 279-299
    CrossrefPubMedGoogle Scholar
  • 76 Naing LY, Heckroth M, Mathur P, Abell TL. Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities. Expert Opin Investig Drugs 2023; 32 (03) 245-262
    CrossrefPubMedGoogle Scholar