title: New perspectives in the diagnosis and management of enteric neuropathies.
abstract: Chronic disturbances of gastrointestinal function encompass a wide spectrum of clinical disorders that range from common conditions with mild-to-moderate symptoms to rare diseases characterized by a severe impairment of digestive function, including chronic pain, vomiting, bloating and severe constipation. Patients at the clinically severe end of the spectrum can have profound changes in gut transit and motility. In a subset of these patients, histopathological analyses have revealed abnormalities of the gut innervation, including the enteric nervous system, termed enteric neuropathies. This Review discusses advances in the diagnosis and management of the main clinical entities--achalasia, gastroparesis, intestinal pseudo-obstruction and chronic constipation--that result from enteric neuropathies, including both primary and secondary forms. We focus on the various evident neuropathologies (degenerative and inflammatory) of these disorders and, where possible, present the specific implications of histological diagnosis to contemporary treatment. This knowledge could enable the future development of novel targeted therapeutic approaches.
authors: Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK.
authors: Charles H
authors: CH
authors: Knowles
authors: Greger
authors: G
authors: Lindberg
authors: Emanuele
authors: E
authors: Panza
authors: Roberto
authors: R
authors: De Giorgio
mesh_terms: D003248:Constipation / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D017615:Enteric Nervous System / Q000503:physiopathology*; D004931:Esophageal Achalasia / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D005769:Gastrointestinal Motility / Q000502:physiology; D041981:Gastrointestinal Tract / Q000294:innervation* / Q000503:physiopathology*; D018589:Gastroparesis / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D011788:Quality of Life
references: Am J Surg Pathol. 2000 Aug;24(8):1153-8
references: 10935657
references: Gastroenterology. 2006 Apr;130(5):1466-79
references: 16678560
references: Ann Thorac Surg. 2005 Oct;80(4):1196-201
references: 16181840
references: Clin Gastroenterol Hepatol. 2005 May;3(5):449-58
references: 15880314
references: Am J Gastroenterol. 2001 Feb;96(2):373-9
references: 11232678
references: Gastroenterology. 2002 Dec;123(6):1972-9
references: 12454854
references: Genet Med. 2011 Sep;13(9):755-64
references: 21552134
references: Am J Gastroenterol. 2003 May;98(5):1052-7
references: 12809827
references: Gastroenterology. 2008 Dec;135(6):2055-64, 2064.e1-2
references: 18926825
references: Aust Fam Physician. 1996 Sep;25(9):1357
references: 8840558
references: Neurogastroenterol Motil. 2004 Oct;16(5):515-31
references: 15500508
references: Aliment Pharmacol Ther. 2008 Jul;28(1):25-42
references: 18410560
references: Gastroenterology. 2006 Feb;130(2 Suppl 1):S43-51
references: 16473071
references: Am J Trop Med Hyg. 1997 May;56(5):485-9
references: 9180594
references: Gut. 2009 Jan;58(1):25-32
references: 18593810
references: Br J Surg. 1984 Jul;71(7):547-52
references: 6733431
references: J Pharmacol Exp Ther. 1994 Nov;271(2):660-70
references: 7525940
references: J Pediatr Surg. 1981 Apr;16(2):164-70
references: 7241318
references: Gastroenterology. 2004 Mar;126(3):693-702
references: 14988823
references: Gut. 2003 May;52(5):752-5
references: 12692064
references: Eur J Pharmacol. 1994 Apr 21;256(2):125-9
references: 7519557
references: Gastroenterology. 1977 Aug;73(2):327-38
references: 873134
references: Hum Pathol. 2011 Apr;42(4):522-32
references: 21208643
references: Support Care Cancer. 2012 Feb;20(2):425-8
references: 22072051
references: J Gastroenterol Hepatol. 2002 Feb;17 Suppl:S1-14
references: 12000590
references: Transplant Proc. 2010 Jan-Feb;42(1):9-14
references: 20172270
references: Best Pract Res Clin Gastroenterol. 2011 Feb;25(1):43-57
references: 21382578
references: J Pediatr Gastroenterol Nutr. 2009 Jan;48(1):22-9
references: 19172119
references: Dig Dis Sci. 1989 Dec;34(12):1937-42
references: 2557192
references: Exp Clin Endocrinol Diabetes. 2005 Jan;113(1):38-42
references: 15662594
references: J Emerg Med. 2012 Dec;43(6):992-5
references: 21719232
references: Gastroenterology. 2010 Feb;138(2):789-91; author reply 791-2
references: 20026445
references: Neurogastroenterol Motil. 2006 Sep;18(9):823-30
references: 16918761
references: J Pediatr Gastroenterol Nutr. 2007 Dec;45 Suppl 2:S110-4
references: 18185070
references: Gastroenterology. 1985 Jan;88(1 Pt 1):26-34
references: 3964770
references: Prog Neurobiol. 2012 Feb;96(2):176-89
references: 22266104
references: J Gastroenterol Hepatol. 2002 Jun;17(6):666-70
references: 12100611
references: Expert Rev Neurother. 2012 Jun;12(6):697-706
references: 22650172
references: Dig Dis Sci. 2010 Feb;55(2):359-70
references: 19997975
references: Histopathology. 2009 Apr;54(5):539-49
references: 19413636
references: Gastroenterology. 2010 Aug;139(2):553-63, 563.e1-5
references: 20347820
references: Gut. 2004 Nov;53(11):1583-9
references: 15479676
references: Gut. 1997 Nov;41(5):675-81
references: 9414977
references: Dig Dis Sci. 2002 Oct;47(10):2298-305
references: 12395903
references: Eur J Gastroenterol Hepatol. 2000 Jun;12(6):613-6
references: 10912477
references: Expert Rev Neurother. 2012 Feb;12(2):239-48
references: 22288679
references: Gut. 2010 Jul;59(7):882-7
references: 20581236
references: Semin Oncol. 2006 Jun;33(3):270-98
references: 16769417
references: J Neurosci. 2009 Aug 5;29(31):9683-99
references: 19657021
references: Eur Neurol. 1997;38 Suppl 2:2-7
references: 9387796
references: Aliment Pharmacol Ther. 2012 Jan;35(1):48-55
references: 22061077
references: Am J Gastroenterol. 2000 Apr;95(4):974-80
references: 10763947
references: Pain Res Treat. 2012;2012:265605
references: 22619712
references: Muscle Nerve. 1999 Nov;22(11):1600-2
references: 10514242
references: Mem Inst Oswaldo Cruz. 2002 Jan;97(1):3-24
references: 11992141
references: N Engl J Med. 2011 May 12;364(19):1807-16
references: 21561346
references: Neurogastroenterol Motil. 2011 Feb;23(2):115-24
references: 21175997
references: N Engl J Med. 2008 May 29;358(22):2344-54
references: 18509121
references: Mov Disord. 2007 Jul 15;22(9):1239-44
references: 17566120
references: Neurogastroenterol Motil. 2008 Jan;20(1):8-18
references: 18173559
references: Neurology. 1998 Mar;50(3):652-7
references: 9521251
references: Am J Gastroenterol. 1962 May;37:541-5
references: 13907162
references: Gut. 1998 Jul;43(1):117-22
references: 9771415
references: Neurogastroenterol Motil. 2006 May;18(5):369-75
references: 16629864
references: Gastroenterology. 1999 Oct;117(4):798-805
references: 10500061
references: Gastroenterology. 2003 Aug;125(2):421-8
references: 12891544
references: Postgrad Med J. 2006 Dec;82(974):788-98
references: 17148699
references: Neurogastroenterol Motil. 2007 Dec;19(12):951-60
references: 17971027
references: Am J Gastroenterol. 2008 Apr;103(4):856-64
references: 18070236
references: J Gastrointestin Liver Dis. 2006 Sep;15(3):237-41
references: 17013448
references: Gastroenterology. 2002 Jun;122(7):1778-83
references: 12055584
references: Arch Intern Med. 2001 Sep 10;161(16):1989-96
references: 11525701
references: Dig Dis Sci. 2011 Dec;56(12):3507-16
references: 21710226
references: Trends Parasitol. 2005 Nov;21(11):513-6
references: 16125464
references: Dis Colon Rectum. 1976 May-Jun;19(4):314-20
references: 819236
references: J Pediatr Surg. 1996 Apr;31(4):580-3
references: 8801318
references: Gastroenterology. 1997 Apr;112(4):1366-71
references: 9098023
references: J Neuropathol Exp Neurol. 1996 Mar;55(3):259-72
references: 8786384
references: ScientificWorldJournal. 2007 Nov 02;7:98-111
references: 17982582
references: J Pediatr Gastroenterol Nutr. 2008 Apr;46(4):457-60
references: 18367961
references: Parkinsonism Relat Disord. 2005 Dec;11(8):499-502
references: 16263322
references: Am J Surg Pathol. 1994 Apr;18(4):327-37
references: 8141427
references: Neurogastroenterol Motil. 2007 Jan;19(1 Suppl):1-19
references: 17280582
references: Am J Gastroenterol. 2002 Jul;97(7):1828-33
references: 12135044
references: Neurogastroenterol Motil. 2008 Dec;20(12):1298-305
references: 18662329
references: Gastroenterology. 1991 Jan;100(1):137-42
references: 1845756
references: Gastroenterology. 2011 May;140(5):1575-85.e8
references: 21300066
references: J Neurol Neurosurg Psychiatry. 2007 Oct;78(10):1163-4
references: 17878201
references: Gut. 1999 Jun;44(6):853-61
references: 10323889
references: Neurogastroenterol Motil. 2007 Jun;19(6):440-52
references: 17564625
references: Gastroenterology. 1996 Sep;111(3):648-54
references: 8780569
references: Ann Intern Med. 1958 Apr;48(4):797-812
references: 13521605
references: Ann Intern Med. 1984 Sep;101(3):331-4
references: 6147108
references: Nat Rev Gastroenterol Hepatol. 2012 Mar 06;9(5):286-94
references: 22392290
references: Br J Surg. 1977 May;64(5):313-4
references: 861466
references: Pediatr Blood Cancer. 2009 Mar;52(3):396-8
references: 18989884
references: Cell Tissue Res. 2012 Aug;349(2):473-81
references: 22555304
references: Gastroenterology. 2000 Sep;119(3):766-73
references: 10982771
references: Gastroenterol Clin North Am. 2011 Dec;40(4):845-51
references: 22100122
references: Biochem Biophys Res Commun. 2011 Apr 29;408(1):1-5
references: 21439933
references: Arch Dis Child. 1999 Jul;81(1):21-7
references: 10373127
references: Clin Biochem. 2008 Dec;41(18):1454-60
references: 18793627
references: Diabetes Care. 2004 May;27(5):1071-6
references: 15111523
references: Dis Colon Rectum. 2002 Jan;45(1):54-62
references: 11786765
references: Acta Neuropathol. 2012 Nov;124(5):665-80
references: 22941241
references: Neurogastroenterol Motil. 2011 Feb;23(2):131-8, e26
references: 20939847
references: Am J Gastroenterol. 1992 Apr;87(4):504-8
references: 1553939
references: Gastroenterol Clin North Am. 2011 Dec;40(4):787-807
references: 22100118
references: Z Gastroenterol. 2008 Mar;46(3):274-8
references: 18322883
references: Gut. 1992 Jul;33(7):1000-3
references: 1644319
references: Neurogastroenterol Motil. 2011 Dec;23(12):1084-91
references: 21917083
references: Am J Gastroenterol. 2004 Aug;99(8):1585-604
references: 15307881
references: Hum Pathol. 2009 Feb;40(2):244-51
references: 18835625
references: Am J Gastroenterol. 2002 Sep;97(9):2454-9
references: 12358272
references: Prog Neurobiol. 2009 Jan 12;87(1):10-20
references: 18929621
references: Gut. 2009 Aug;58(8):1084-90
references: 19136514
references: Am J Surg Pathol. 1999 May;23(5):602-6
references: 10328094
references: J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):248-53
references: 20639771
references: J Pathol. 2001 Mar;193(3):390-7
references: 11241421
references: Minerva Gastroenterol Dietol. 2011 Jun;57(2):117-21
references: 21587143
references: PLoS One. 2010 Sep 14;5(9):e12728
references: 20856865
references: Ann Surg. 1999 Nov;230(5):627-38
references: 10561086
references: Virchows Arch. 2012 Jan;460(1):123-7
references: 22173330
references: J Pharmacol Sci. 2004 Sep;96(1):1-10
references: 15351789
references: Am J Gastroenterol. 1999 Sep;94(9):2357-62
references: 10483991
references: J Neurol Neurosurg Psychiatry. 2012 Jun;83(6):638-45
references: 22448032
references: J Clin Gastroenterol. 2011 May-Jun;45(5):436-41
references: 21422947
references: Gut. 1992 Feb;33(2):150-4
references: 1541407
references: Acta Neuropathol. 2010 Jun;119(6):689-702
references: 20306269
references: Am J Gastroenterol. 2011 Feb;106(2):329-36
references: 21102570
references: Mov Disord. 1995 Jan;10(1):81-4
references: 7885359
references: Am J Gastroenterol. 2000 Jul;95(7):1759-64
references: 10925981
references: Dig Dis Sci. 1998 Dec;43(12):2719-26
references: 9881505
references: Int J Colorectal Dis. 1998;13(5-6):208-16
references: 9870163
references: Curr Opin Anaesthesiol. 2010 Oct;23(5):616-22
references: 20543677
references: Gastroenterology. 1985 Oct;89(4):882-9
references: 4029567
references: Gastroenterology. 1997 Nov;113(5):1535-44
references: 9352855
references: Gastroenterology. 2004 Jun;126(7):1872-83
references: 15188182
references: Am J Surg Pathol. 2007 Mar;31(3):460-8
references: 17325489
references: Gastroenterology. 2006 May;130(6):1595-606
references: 16697723
references: Auton Neurosci. 2009 Nov 17;151(1):61-9
references: 19783483
references: Dig Dis Sci. 1997 Oct;42(10):2106-10
references: 9365143
references: Stem Cell Rev Rep. 2010 Sep;6(3):367-80
references: 20336395
references: Acta Neuropathol. 1988;76(3):217-221
references: 2850698
references: Acta Neuropathol. 2009 Aug;118(2):271-301
references: 19360428
references: AJR Am J Roentgenol. 1984 Nov;143(5):933-41
references: 6333163
references: Gastroenterol Clin North Am. 2011 Dec;40(4):695-713
references: 22100112
references: Pain. 2009 Feb;141(3):191-209
references: 19155134
references: Gut. 1987 Jan;28(1):5-12
references: 3817584
references: World J Diabetes. 2012 May 15;3(5):80-93
references: 22645637
references: N Engl J Med. 2000 Sep 21;343(12):847-55
references: 10995864
references: Gut. 2009 Oct;58(10):1427-36
references: 19749141
references: Neurogastroenterol Motil. 2006 Apr;18(4):251-62
references: 16553581
references: Dig Dis Sci. 1998 Mar;43(3):506-12
references: 9539644
references: Ann Surg. 2012 Sep;256(3):494-508
references: 22868368
references: Neuroscientist. 2010 Oct;16(5):519-31
references: 20581331
references: Clin Microbiol Rev. 1999 Apr;12(2):210-23
references: 10194457
references: Gastroenterology. 2001 Aug;121(2):427-34
references: 11487552
references: Neurogastroenterol Motil. 2000 Feb;12(1):1
references: 10652110
references: Am J Gastroenterol. 1997 Jun;92(6):976-80
references: 9177513