title: Surgery and risk for multiple sclerosis: a systematic review and meta-analysis of case-control studies.
abstract: BACKGROUND
  Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent risk for developing the disease. Therefore, we aimed to examine surgery as a risk factor for the diagnosis of multiple sclerosis.
  
  
  METHODS
  We searched for observational studies that evaluated the risk for developing multiple sclerosis after surgery that occurred in childhood (≤ 20 years of age) or "premorbid" (> 20 years of age). We specifically included surgeries classified as: tonsillectomy, appendectomy, adenoidectomy, or "surgery". We performed a systematic review and meta-analyses and calculated odds ratios (OR) and their 95% confidence intervals (CIs) using a random effects model.
  
  
  RESULTS
  We identified 33 case-control studies, involving 27,373 multiple sclerosis cases and 211,756 controls. There was a statistically significant association between tonsillectomy (OR = 1.32, 95% CI 1.08-1.61; 12 studies, I(2) = 44%) and appendectomy (OR = 1.16, 95% CI 1.01-1.34; 7 studies, I(2) = 0%) in individual's ≤ 20 years of age and the subsequent risk for developing multiple sclerosis. There was no statistically significant association between risk for multiple sclerosis and tonsillectomy occurring after age 20 (OR = 1.20, 95% CI 0.94-1.53; 9 studies, I(2) = 32%), in those with appendectomy at > 20 years (OR = 1.26, 95% CI 0.92-1.72; 5 studies, I(2) = 46%), and in those with adenoidectomy at ≤ 20 years of age (OR = 1.06, 95% CI 0.68-1.68; 3 studies, I(2) = 35%). The combined OR of 15 studies (N = 2,380) looking at "surgery" before multiple sclerosis diagnosis was not statistically significant (OR = 1.19, 95% CI 0.83-1.70; I(2) = 71%).
  
  
  CONCLUSIONS
  We found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.
authors: Centre for Nursing and Health Studies, Faculty of Health Disciplines, Athabasca University, 1 University Drive Athabasca, Alberta T9S 3A3, Canada.
authors: Carole
authors: C
authors: Lunny
authors: Jennifer A
authors: JA
authors: Knopp-Sihota
authors: Shawn N
authors: SN
authors: Fraser
mesh_terms: D016022:Case-Control Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D006801:Humans; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery*; D012307:Risk Factors
references: Lancet Neurol. 2011 May;10(5):436-45
references: 21459044
references: Acta Neurol Scand. 1996 Dec;94(6):395-403
references: 9017027
references: World J Gastroenterol. 2005 Aug 21;11(31):4869-74
references: 16097061
references: Ann Neurol. 1983 Mar;13(3):227-31
references: 6847134
references: Anat Rec (Hoboken). 2011 Apr;294(4):567-79
references: 21370495
references: Mult Scler. 2000 Apr;6(2):121-3
references: 10773858
references: JAMA. 2005 May 25;293(20):2496-500
references: 15914750
references: Zh Nevrol Psikhiatr Im S S Korsakova. 2009;109(8):59-62
references: 19824132
references: Acta Neurol Scand. 1990 Nov;82(5):303-10
references: 2281747
references: Mult Scler. 2006 Aug;12(4):397-411
references: 16900753
references: Rev Neurol. 2001 Nov 16-30;33(10):931-7
references: 11785004
references: Mult Scler. 2003 Jun;9(3):302-6
references: 12814180
references: Rev Neurol. 1998 Jan;26(149):67-9
references: 9533209
references: Eur J Epidemiol. 2010 Sep;25(9):603-5
references: 20652370
references: Neurology. 2010 Mar 16;74(11):876-7
references: 20231663
references: Acta Neurol Scand Suppl. 1995;161:77-88
references: 7653250
references: Mult Scler. 2011 May;17(5):550-5
references: 21325015
references: Lancet. 1965 Dec 18;2(7425):1264-6
references: 4165404
references: Br Med J. 1950 Aug 19;2(4676):431-6
references: 15434411
references: J Epidemiol Community Health. 1980 Dec;34(4):240-52
references: 7241023
references: Neurology. 1978 Oct;28(10):978-87
references: 570667
references: JAMA. 1974 Jun 17;228(12):1555-7
references: 4406706
references: Arq Neuropsiquiatr. 2009 Jun;67(2A):229-34
references: 19547814
references: Psychosom Med. 2012 Apr;74(3):312-8
references: 22408134
references: Brain. 1957 Dec;80(4):456-78
references: 13499755
references: Br Med J. 1976 Jan 24;1(6003):183-6
references: 764920
references: J Neurol. 1994 Mar;241(5):341-6
references: 8006689
references: J Theor Biol. 2007 Dec 21;249(4):826-31
references: 17936308
references: J Pediatr. 1951 May;38(5):548-58
references: 14832710
references: Rev Med Interna Neurol Psihiatr Neurochir Dermatovenerol Neurol Psihiatr Neurochir. 1981 Jan-Mar;26(1):23-31
references: 6454239
references: Am J Hyg. 1957 Sep;66(2):131-50
references: 13458179
references: J Neurol. 1992 Feb;239(2):93-7
references: 1552310
references: Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99(5):32-40
references: 10358916
references: Ann Neurol. 1994 Dec;36 Suppl 2:S175-9
references: 7998786
references: Arch Surg. 2011 Mar;146(3):308-14
references: 21422362
references: Eur Neurol. 1996;36(2):79-84
references: 8654490
references: Int J Neurosci. 1990 Aug;53(2-4):213-5
references: 2265942
references: Brain. 2008 Jul;131(Pt 7):1712-21
references: 18550621
references: Acta Neurol Scand. 1996 Dec;94(6):386-94
references: 9017026
references: Ital J Neurol Sci. 1987 Jun;Suppl 6:17-20
references: 3654176
references: Mult Scler. 1998 Oct;4(5):419-25
references: 9839302
references: Zh Nevrol Psikhiatr Im S S Korsakova. 2009;109(7 Suppl 2):10-5
references: 19894307
references: Ann Neurol. 2001 Jul;50(1):121-7
references: 11456302
references: Neurology. 1993 Oct;43(10):1878-82
references: 8413941
references: Eur J Neurol. 2011 Apr;18(4):667-9
references: 20629715
references: Neuroepidemiology. 1994;13(3):120-8
references: 8015665
references: Rev Neurol. 2002 May 1-15;34(9):813-6
references: 12134340
references: Med Clin (Barc). 1965 Apr;44(4):252-5
references: 5834781
references: Neuroepidemiology. 1993;12(2):61-9
references: 8232705
references: J Trauma. 1975 May;15(5):459-63
references: 1127774
references: Arch Surg. 2010 Jan;145(1):63-71
references: 20083756
references: Nervenarzt. 1997 Dec;68(12):940-4
references: 9465335
references: Mult Scler. 2011 Oct;17(10):1162-9
references: 21980148
references: Neurol Sci. 2003 Nov;24(4):242-7
references: 14658040
references: Am J Hyg. 1953 May;57(3):380-96
references: 13040327
references: Acta Neurol Scand. 1997 Sep;96(3):149-57
references: 9300067
references: J Neurol. 2009 Jul;256(7):1052-60
references: 19252771
references: Acta Otolaryngol Suppl. 1984;416:30-7
references: 6099955
references: Acta Neurol Scand. 1997 Feb;95(2):90-5
references: 9059727
references: Rev Neurol (Paris). 2003 Apr;159(4):470-86
references: 12795263
references: Neurology. 2004 Mar 9;62(5):726-9
references: 15007121
references: Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99(6):47-52
references: 10441868
references: Clin Neurol Neurosurg. 2006 Mar;108(3):227-33
references: 16406307
references: Curr Opin Rheumatol. 2012 Jul;24(4):424-8
references: 22617821
references: Acta Neurol Scand Suppl. 1989;124:1-123
references: 2683558
references: BMC Neurol. 2011 Oct 06;11:123
references: 21978074
references: CNS Neurol Disord Drug Targets. 2012 Aug;11(5):545-55
references: 22583442
references: Ann Neurol. 2007 Apr;61(4):288-99
references: 17444504
references: Neuroepidemiology. 1992;11(2):90-9
references: 1495579
references: JAMA. 2000 Apr 19;283(15):2008-12
references: 10789670
references: J Neurol. 1981;225(4):237-49
references: 6169803
references: Eur J Neurol. 2010 Sep;17(9):1210-1214
references: 20345929
references: Arch Neurol. 1965 Aug;13:183-93
references: 14315670
references: Arch Neurol. 1982 Mar;39(3):140-4
references: 7199899
references: Acta Neurol Scand. 1989 Jul;80(1):46-50
references: 2782041
references: Lancet. 2002 Apr 6;359(9313):1221-31
references: 11955556
references: Eur Neurol. 1969;2(2):90-108
references: 5819891
references: Neuroepidemiology. 1991;10(4):192-9
references: 1745329
references: Neurology. 1974 Aug;24(8):748-54
references: 4858420
references: Autoimmune Dis. 2012;2012:189096
references: 22312480
references: Am J Public Health Nations Health. 1968 May;58(5):836-48
references: 5689628
references: Ann N Y Acad Sci. 1955 Sep 27;61(4):856-68
references: 13340593
references: Am J Epidemiol. 2011 Oct 15;174(8):945-8
references: 21920946
references: J Clin Epidemiol. 2000 Nov;53(11):1188
references: 11186614
references: Mult Scler. 2008 Apr;14(3):307-13
references: 18208871
references: J Neurol Neurosurg Psychiatry. 2011 Oct;82(10):1132-41
references: 21478203
references: JAMA. 2006 Feb 8;295(6):676-80
references: 16467236
references: Acta Neurol Scand. 1981 Feb;63(2):131-5
references: 7211178
references: Lakartidningen. 1966 Apr 6;63(14):1318-9
references: 5917042
references: Neurol Sci. 2001 Apr;22(2):117-39
references: 11603614
references: Lancet Neurol. 2008 Sep;7(9):852-8
references: 18703007
references: Acta Neurol Scand Suppl. 1995;161:34-42
references: 7653243
references: Acta Neurol Scand. 2008 Jan;117(1):15-20
references: 18095952
references: Gastroenterology. 2005 Sep;129(3):827-36
references: 16143122
references: CNS Spectr. 2008 May;13(5):361-2
references: 18496473
references: Acta Neurol Scand Suppl. 1995;161:71-6
references: 7653249
references: Schweiz Arch Neurol Neurochir Psychiatr. 1970;106(2):311-7
references: 5458853
references: J Neurol Neurosurg Psychiatry. 2011 Oct;82(10):1142-8
references: 21836034
references: J Chronic Dis. 1967 May;20(5):311-32
references: 6026359
references: Zh Nevrol Psikhiatr Im S S Korsakova. 2002;Suppl:3-6
references: 12418385
references: Int J Epidemiol. 1998 Aug;27(4):667-71
references: 9758123
references: Zh Nevrol Psikhiatr Im S S Korsakova. 2006;Spec No 3:4-10
references: 17172228
references: AMA Arch Neurol Psychiatry. 1954 Apr;71(4):511-6
references: 13147609
references: Neurology. 1968 Feb;18(2):109-16
references: 5688752
references: Ann Neurol. 2006 Mar;59(3):499-503
references: 16502434
references: Neuroepidemiology. 1991;10(1):9-17
references: 2062417
references: Mult Scler. 2008 Jan;14(1):136-9
references: 17942525