title: Neurological disorders and inflammatory bowel diseases.
abstract: Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.
authors.affiliation: Giovanni Casella, Vittorio Baldini, Medical Department, Desio Hospital, 20033 Desio, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casella
authors.affiliation: Giovanni Casella, Vittorio Baldini, Medical Department, Desio Hospital, 20033 Desio, Italy.
authors.forename: Gian Eugenio
authors.initials: GE
authors.lastname: Tontini
authors.affiliation: Giovanni Casella, Vittorio Baldini, Medical Department, Desio Hospital, 20033 Desio, Italy.
authors.forename: Gabrio
authors.initials: G
authors.lastname: Bassotti
authors.affiliation: Giovanni Casella, Vittorio Baldini, Medical Department, Desio Hospital, 20033 Desio, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pastorelli
authors.affiliation: Giovanni Casella, Vittorio Baldini, Medical Department, Desio Hospital, 20033 Desio, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villanacci
authors.affiliation: Giovanni Casella, Vittorio Baldini, Medical Department, Desio Hospital, 20033 Desio, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Spina
authors.affiliation: Giovanni Casella, Vittorio Baldini, Medical Department, Desio Hospital, 20033 Desio, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Baldini
authors.affiliation: Giovanni Casella, Vittorio Baldini, Medical Department, Desio Hospital, 20033 Desio, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Vecchi
mesh_terms: D000818:Animals; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control; D005765:Gastrointestinal Agents / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control; D012307:Risk Factors
chemical_list: D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents
keywords: Cerebrovascular diseases; Crohn’s disease; Demyelinating neuropathies; Extraintestinal manifestations; Inflammatory bowel diseases; Multiple sclerosis; Neurological disorders; Progressive multifocal encephalopathy; Side effects; Ulcerative colitis
references.citation: Nat Clin Pract Gastroenterol Hepatol. 2005 Jun;2(6):266-72
references.pmid: 16265230
references.citation: Brain. 2005 Apr;128(Pt 4):867-79
references.pmid: 15705608
references.citation: Postgrad Med J. 2003 Jan;79(927):11-7
references.pmid: 12566545
references.citation: Neurology. 2007 May 8;68(19):1563-70
references.pmid: 17460157
references.citation: Crit Care Med. 2004 May;32(5 Suppl):S266-70
references.pmid: 15118529
references.citation: Am J Gastroenterol. 2003 Jan;98(1):112-7
references.pmid: 12526945
references.citation: Semin Arthritis Rheum. 2007 Feb;36(4):262-3
references.pmid: 17067660
references.citation: J Clin Rheumatol. 2002 Apr;8(2):85-8
references.pmid: 17041328
references.citation: J Clin Gastroenterol. 1987 Dec;9(6):627-31
references.pmid: 3443729
references.citation: Eye (Lond). 2006 Oct;20(10):1196-206
references.pmid: 17019419
references.citation: Aust N Z J Ophthalmol. 1998 Nov;26(4):329-32
references.pmid: 9843262
references.citation: J Neurol Sci. 2010 Apr 15;291(1-2):103-6
references.pmid: 20116808
references.citation: Int J Stroke. 2009 Apr;4(2):111-23
references.pmid: 19383052
references.citation: Clin Infect Dis. 2007 Oct 1;45(7):875-80
references.pmid: 17806053
references.citation: Pediatrics. 1998 Jan;101(1):E10
references.pmid: 9417174
references.citation: Eur J Intern Med. 2005 Oct;16(6):440-2
references.pmid: 16198906
references.citation: Medicine (Baltimore). 1976 Sep;55(5):401-12
references.pmid: 957999
references.citation: Neurology. 1995 Mar;45(3 Pt 1):416-21
references.pmid: 7898687
references.citation: Aliment Pharmacol Ther. 2009 Feb 1;29(3):286-97
references.pmid: 19132970
references.citation: World J Gastroenterol. 2005 Dec 14;11(46):7227-36
references.pmid: 16437620
references.citation: Am J Gastroenterol. 2010 Jan;105(1):240-1
references.pmid: 20054331
references.citation: Gastroenterology. 2005 Sep;129(3):819-26
references.pmid: 16143121
references.citation: Neurology. 2003 Aug 12;61(3):375-82
references.pmid: 12913201
references.citation: J Crohns Colitis. 2011 Jun;5(3):249-52
references.pmid: 21575890
references.citation: Aliment Pharmacol Ther. 2001 Oct;15(10):1515-25
references.pmid: 11563990
references.citation: Eur J Gastroenterol Hepatol. 2007 Feb;19(2):159-62
references.pmid: 17273002
references.citation: Lancet. 1990 Feb 17;335(8686):409-10
references.pmid: 1968133
references.citation: Arch Soc Esp Oftalmol. 2001 Mar;76(3):189-91
references.pmid: 11283786
references.citation: N Engl J Med. 2005 Jul 28;353(4):414-6
references.pmid: 15947082
references.citation: Neurology. 1999 Aug 11;53(3):457-65
references.pmid: 10449104
references.citation: J Rheumatol. 2012 Sep;39(9):1906-7
references.pmid: 22942312
references.citation: Clin Exp Rheumatol. 2008 Jul-Aug;26(4):671-2
references.pmid: 18799104
references.citation: Dig Dis Sci. 2005 Oct;50(10):1938-45
references.pmid: 16187200
references.citation: Aliment Pharmacol Ther. 2013 Aug;38(4):388-96
references.pmid: 23802849
references.citation: J Neurovirol. 2010 Feb;16(1):1-5
references.pmid: 20113184
references.citation: Arthritis Rheum. 2001 Dec;44(12):2862-9
references.pmid: 11762947
references.citation: Thromb Haemost. 1998 Oct;80(4):542-5
references.pmid: 9798965
references.citation: Medicine (Baltimore). 2007 Jul;86(4):242-251
references.pmid: 17632266
references.citation: Lancet. 2007 May 12;369(9573):1627-40
references.pmid: 17499605
references.citation: J Neurol. 2001 Jan;248(1):57-60
references.pmid: 11266021
references.citation: Gut. 2008 Apr;57(4):549-58
references.pmid: 18178610
references.citation: Am J Gastroenterol. 1993 Jul;88(7):1136-8
references.pmid: 8317426
references.citation: Dig Dis Sci. 2004 Mar;49(3):469-74
references.pmid: 15139501
references.citation: Lancet. 1985 Jan 26;1(8422):219-20
references.pmid: 2857289
references.citation: Scand J Gastroenterol. 1996 Aug;31(8):792-6
references.pmid: 8858749
references.citation: J Rheumatol. 2008 Mar;35(3):539-42
references.pmid: 18322977
references.citation: Curr Opin Ophthalmol. 2006 Dec;17(6):538-44
references.pmid: 17065922
references.citation: Muscle Nerve. 2008 Mar;37(3):281-92
references.pmid: 18041052
references.citation: N Engl J Med. 2005 Jul 28;353(4):362-8
references.pmid: 15947080
references.citation: N Engl J Med. 2005 Jun 16;352(24):2499-507
references.pmid: 15958805
references.citation: Inflamm Bowel Dis. 2008 Jul;14(7):977-83
references.pmid: 18275078
references.citation: Cytokine. 2009 Feb;45(2):55-7
references.pmid: 19109035
references.citation: Graefes Arch Clin Exp Ophthalmol. 2010 Feb;248(2):283-7
references.pmid: 19916016
references.citation: J Gastroenterol Hepatol. 2007 Nov;22(11):1748-53
references.pmid: 17914945
references.citation: Am J Gastroenterol. 2004 Oct;99(10):1966-70
references.pmid: 15447757
references.citation: J Clin Sleep Med. 2006 Oct 15;2(4):409-16
references.pmid: 17557469
references.citation: J Clin Gastroenterol. 1994 Apr;18(3):213-7
references.pmid: 8034917
references.citation: N Engl J Med. 2006 Mar 2;354(9):924-33
references.pmid: 16510746
references.citation: J Pediatr Gastroenterol Nutr. 2010 Mar;50(3):353
references.pmid: 20190611
references.citation: Inflamm Bowel Dis. 2013 Mar-Apr;19(4):864-72
references.pmid: 22552994
references.citation: Thromb J. 2008 Mar 21;6:2
references.pmid: 18358077
references.citation: Neurology. 1982 Sep;32(9):958-64
references.pmid: 7202168
references.citation: J Clin Sleep Med. 2008 Feb 15;4(1):45-9
references.pmid: 18350962
references.citation: BMC Psychiatry. 2009 Oct 23;9 Suppl 1:S1
references.pmid: 19857242
references.citation: Open Rheumatol J. 2009 Jul 13;3:30-4
references.pmid: 19639039
references.citation: Inflamm Bowel Dis. 2009 Apr;15(4):576-80
references.pmid: 19023898
references.citation: N Engl J Med. 2003 Jan 2;348(1):24-32
references.pmid: 12510039
references.citation: Clin Neurol Neurosurg. 2012 Jul;114(6):725-7
references.pmid: 22225972
references.citation: Lancet. 1995 Apr 8;345(8954):897-8
references.pmid: 7707814
references.citation: J Exp Med. 2001 Feb 19;193(4):427-34
references.pmid: 11181695
references.citation: Scand J Gastroenterol. 1991 Feb;26(2):219-24
references.pmid: 1849313
references.citation: J Rheumatol. 2010 Aug 1;37(8):1778-80
references.pmid: 20675855
references.citation: Arch Neurol. 2005 Nov;62(11):1673-80
references.pmid: 16286539
references.citation: J Cancer Res Ther. 2012 Apr-Jun;8(2):292-6
references.pmid: 22842379
references.citation: J Clin Gastroenterol. 2009 May-Jun;43(5):499
references.pmid: 19247199
references.citation: Gut. 2004 Apr;53(4):542-8
references.pmid: 15016749
references.citation: Gastroenterol Hepatol (N Y). 2012 Aug;8(8):504-12
references.pmid: 23293563
references.citation: Gastroenterology. 1985 Mar;88(3):681-4
references.pmid: 2981752
references.citation: J Crohns Colitis. 2010 Jun;4(2):115-24
references.pmid: 21122494
references.citation: Eur J Neurol. 2007 May;14(5):483-93
references.pmid: 17437605
references.citation: Rheumatology (Oxford). 2005 Sep;44(9):1132-5
references.pmid: 15927999
references.citation: JAMA. 2006 Jul 19;296(3):283-91
references.pmid: 16849661
references.citation: Inflamm Bowel Dis. 2009 May;15(5):645-6
references.pmid: 18798576
references.citation: AJNR Am J Neuroradiol. 2005 Jun-Jul;26(6):1548-50
references.pmid: 15956528
references.citation: J Gastroenterol Hepatol. 2004 Sep;19(9):1093-4
references.pmid: 15304135
references.citation: Neurology. 2005 Apr 26;64(8):1468-70
references.pmid: 15851749
references.citation: N Engl J Med. 1986 Feb 27;314(9):586
references.pmid: 3945303
references.citation: Int J Toxicol. 2007;26 Suppl 3:31-77
references.pmid: 18080873
references.citation: Clin Immunol. 2008 Jan;126(1):13-30
references.pmid: 17916445
references.citation: Muscle Nerve. 2010 May;41(5):723-7
references.pmid: 20405504
references.citation: Drugs. 1986;32 Suppl 1:1-11
references.pmid: 2877847
references.citation: Lancet. 1984 Nov 17;2(8412):1116-20
references.pmid: 6150182
references.citation: Am J Gastroenterol. 2000 Mar;95(3):841-2
references.pmid: 10710107
references.citation: Inflamm Bowel Dis. 2010 Sep;16(9):1450-3
references.pmid: 20128005
references.citation: N Engl J Med. 2005 Apr 28;352(17):1791-8
references.pmid: 15858188
references.citation: JAMA. 2009 Feb 18;301(7):737-44
references.pmid: 19224750
references.citation: Sleep Med. 2004 Jul;5(4):385-91
references.pmid: 15222997
references.citation: Neurol Clin. 2010 Feb;28(1):107-70
references.pmid: 19932379
references.citation: Dig Dis Sci. 2005 Feb;50(2):235-40
references.pmid: 15745078
references.citation: Bull Tokyo Dent Coll. 1990 May;31(2):137-41
references.pmid: 2131166
references.citation: Am J Otolaryngol. 2009 May-Jun;30(3):166-70
references.pmid: 19410121
references.citation: Clin Immunol. 2003 Feb;106(2):73-82
references.pmid: 12672398
references.citation: Arch Neurol. 2009 Apr;66(4):490-7
references.pmid: 19364934
references.citation: Am J Gastroenterol. 2001 Sep;96(9):2778-82
references.pmid: 11569712
references.citation: N Engl J Med. 2005 Jul 28;353(4):375-81
references.pmid: 15947078
references.citation: Br J Rheumatol. 1993 Dec;32(12):1105-8
references.pmid: 8252324
references.citation: Clin Infect Dis. 2009 Sep 15;49(6):924-7
references.pmid: 19681709
references.citation: Pharmacol Rep. 2005 Jan-Feb;57(1):23-34
references.pmid: 15849374
references.citation: J Crohns Colitis. 2012 Oct;6(9):946-9
references.pmid: 22749231
references.citation: Scand J Infect Dis. 2008;40(1):59-62
references.pmid: 17852910
references.citation: J Crohns Colitis. 2011 Dec;5(6):619-22
references.pmid: 22115384
references.citation: Surg Neurol. 2006 Feb;65(2):178-84; discussion 184
references.pmid: 16427419
references.citation: Epileptic Disord. 2011 Jun;13(2):214-7
references.pmid: 21636356
references.citation: J Gastrointestin Liver Dis. 2011 Jun;20(2):201-3
references.pmid: 21725519
references.citation: Scand J Gastroenterol. 2009;44(10):1268-9
references.pmid: 19681018
references.citation: J Neurol Sci. 2006 Sep 25;247(2):236-8
references.pmid: 16815466
references.citation: Scand J Rheumatol. 2008 Sep-Oct;37(5):397-9
references.pmid: 18720264
references.citation: Gut. 1994 Feb;35(2):278-9
references.pmid: 8307484
references.citation: Clin Infect Dis. 2002 Apr 15;34(8):1154-7
references.pmid: 11915008
references.citation: N Engl J Med. 2005 Oct 6;353(14):1530-1; discussion 1530-1
references.pmid: 16207863
references.citation: N Engl J Med. 2005 Dec 8;353(23):2462-76
references.pmid: 16339095
references.citation: Inflamm Bowel Dis. 2008 Mar;14(3):389-95
references.pmid: 17924556
references.citation: Case Rep Neurol Med. 2013;2013:671935
references.pmid: 23762678
references.citation: Neurology. 2005 Nov 22;65(10):1652-3
references.pmid: 16301499
references.citation: Altern Med Rev. 2007 Jun;12(2):101-12
references.pmid: 17604457
references.citation: Br J Ophthalmol. 2003 Sep;87(9):1186-7
references.pmid: 12928296
references.citation: Arch Intern Med. 1985 Feb;145(2):289-92
references.pmid: 3977489
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G5-G18
references.pmid: 17463183
references.citation: J Neurol Sci. 1998 May 7;157(2):148-53
references.pmid: 9619637
references.citation: Clin Infect Dis. 1995 May;20(5):1428-9
references.pmid: 7620039
references.citation: Med Clin North Am. 2004 May;88(3):653-67, viii
references.pmid: 15087209
references.citation: Psychol Health Med. 2010 Aug;15(4):394-405
references.pmid: 20677078
references.citation: J Laryngol Otol. 1991 Apr;105(4):330-1
references.pmid: 2026952
references.citation: J Crohns Colitis. 2013 Apr;7(3):e115
references.pmid: 22868065
references.citation: Ann Rheum Dis. 2007 Sep;66(9):1255-8
references.pmid: 17456525
references.citation: Am J Ophthalmol. 1998 Oct;126(4):607-9
references.pmid: 9780114
references.citation: Clin Exp Rheumatol. 2004 Sep-Oct;22(5 Suppl 35):S134-40
references.pmid: 15552527
references.citation: Inflamm Bowel Dis. 2007 Jul;13(7):896-902
references.pmid: 17345605
references.citation: Clin Neuropharmacol. 2008 Nov-Dec;31(6):368-71
references.pmid: 19050416
references.citation: Braz J Otorhinolaryngol. 2006 Jul-Aug;72(4):572
references.pmid: 17143440
references.citation: Fortschr Neurol Psychiatr. 1996 Oct;64(10):422-4
references.pmid: 9036102
references.citation: Immunology. 1990 Jan;69(1):33-7
references.pmid: 2107144
references.citation: Neurology. 1986 May;36(5):719-21
references.pmid: 3703273
references.citation: BMQ. 1962 Jun;13:62-6
references.pmid: 13914712
references.citation: Rev Infect Dis. 1989 Nov-Dec;11(6):954-63
references.pmid: 2690289
references.citation: J Crohns Colitis. 2013 Feb;7(1):e19
references.pmid: 22742971
references.citation: Keio J Med. 1989 Dec;38(4):383-402
references.pmid: 2698424
references.citation: Inflamm Bowel Dis. 2004 Jan;10(1):28-31
references.pmid: 15058523
references.citation: Gastroenterology. 2005 Sep;129(3):827-36
references.pmid: 16143122
references.citation: Pediatr Radiol. 2010 Aug;40(8):1453
references.pmid: 19915830
references.citation: Nihon Kyobu Shikkan Gakkai Zasshi. 1994 Apr;32(4):358-63
references.pmid: 8041047
references.citation: Am J Med Sci. 2011 Nov;342(5):352-5
references.pmid: 21876428
references.citation: Clin Infect Dis. 2008 Aug 1;47(3):303-27
references.pmid: 18582201
references.citation: Eur Rev Med Pharmacol Sci. 2004 Sep-Oct;8(5):205-8
references.pmid: 15638231
references.citation: Am J Gastroenterol. 2005 Sep;100(9):2036-41
references.pmid: 16128949
references.citation: J Infect Dis. 2007 Sep 15;196(6):853-60
references.pmid: 17703415
references.citation: Infection. 1993 Sep-Oct;21(5):331-3
references.pmid: 8300253
references.citation: JAMA. 2004 Jan 28;291(4):427-34
references.pmid: 14747499
references.citation: BMJ. 2003 Mar 15;326(7389):579
references.pmid: 12637403
references.citation: Neurosurg Focus. 1999 Jun 15;6(6):E12
references.pmid: 16972747
references.citation: Clin Otolaryngol Allied Sci. 2000 Apr;25(2):143-5
references.pmid: 10816220
references.citation: J Gastrointestin Liver Dis. 2013 Mar;22(1):21-5
references.pmid: 23539386
references.citation: Am J Med Sci. 1993 Jan;305(1):28-35
references.pmid: 8416679
references.citation: Arthritis Rheum. 2001 Sep;44(9):1977-83
references.pmid: 11592357
references.citation: J Pediatr Gastroenterol Nutr. 1989 Apr;8(3):413-20
references.pmid: 2651640
references.citation: Rheumatology (Oxford). 2009 Jul;48(7):716-20
references.pmid: 19416947
references.citation: Arthritis Rheum. 2006 May;54(5):1429-34
references.pmid: 16645971
references.citation: Reumatismo. 2010 Oct-Dec;62(4):283-5
references.pmid: 21253622
references.citation: J Gastroenterol. 2002;37(4):297-302
references.pmid: 11993515
references.citation: Inflamm Bowel Dis. 2010 Feb;16(2):275-9
references.pmid: 19575360
references.citation: Clin Imaging. 2008 May-Jun;32(3):227-9
references.pmid: 18502352
references.citation: J Clin Invest. 2004 May;113(9):1271-6
references.pmid: 15124018