Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS). Trauma to the CNS has been postulated to play a role in triggering CNS autoimmune disease. Although the association between traumatic brain injury and MS has been suggested in previous studies, epidemiological data on the association between spinal cord injury (SCI) and MS is still lacking. The aim of the present population-based, propensity score–matched, longitudinal follow-up study was therefore to investigate whether patients with SCI were at a higher risk of developing MS. A total of 11,913 subjects ages between 20 and 90 years with at least two ambulatory visits with the principal diagnosis of SCI in 2001 were enrolled in the SCI group. We used a logistic regression model that included age, sex, pre-existing comorbidities, and socioeconomic status as covariates to compute the propensity score. The non-SCI group consisted of 59,565 propensity score–matched, randomly sampled subjects without SCI. Stratified Cox proportional hazard regression with patients matched by propensity score was used to estimate the effect of SCI on the risk of developing subsequent MS. During follow-up, five subjects in the SCI group and four in the non-SCI group developed MS. The incidence rates of MS were 17.60 (95% confidence interval [CI], 5.71-41.0) per 100,000 person-years in the SCI group and 2.82 (95% CI, 0.77-7.22) per 100,000 person-years in the non-SCI group. Compared with the non-SCI group, the hazard ratio of MS for the SCI group was 8.33 (95% CI, 1.99-34.87, p=0.0037). Our study therefore shows that patients with SCI have an increased risk of developing MS.
Get full access to this article
View all access options for this article.
References
1.
NoseworthyJ.H., LucchinettiC., RodriguezM., and WeinshenkerB.G. (2000). Multiple sclerosis. N. Engl. J. Med., 343, 938–952.
2.
HauserS.L. and OksenbergJ.R. (2006). The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron, 52, 61–76.
3.
HohlfeldR. (1997). Biotechnological agents for the immunotherapy of multiple sclerosis. Principles, problems and perspectives. Brain, 120 ( Pt 5), 865–916.
4.
PoserC.M. (1994). The role of trauma in the pathogenesis of multiple sclerosis: a review. Clin. Neurol. Neurosurg., 96, 103–110.
5.
PoserC.M. (2000). Trauma to the central nervous system may result in formation or enlargement of multiple sclerosis plaques. Arch. Neurol., 57, 1074–1077.
6.
KurlandL.T. (1994). Trauma and multiple sclerosis. Ann. Neurol., 36Suppl, S33–37.
7.
GoldacreM.J., AbisgoldJ.D., YeatesD.G., and SeagroattV. (2006). Risk of multiple sclerosis after head injury: record linkage study. J. Neurol. Neurosurg. Psychiatry, 77, 351–353.
8.
PflegerC.C., Koch-HenriksenN., StenagerE., FlachsE.M., and JohansenC. (2009). Head injury is not a risk factor for multiple sclerosis: a prospective cohort study. Mult. Scler., 15, 294–298.
9.
KangJ.H. and LinH.C. (2012). Increased risk of multiple sclerosis after traumatic brain injury: a nationwide population-based study. J. Neurotrauma, 29, 90–95.
10.
ParsonsL.S. (2004). Performing a 1:N Case-Control Match on Propensity Score. Proceedings of the 29th Annual SAS Users Group International Conference; Québec, Canada.
11.
D'AgostinoR.B.Jr. (1998). Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat. Med., 17, 2265–2281.
BufillE., BlesaR., GalanI., and DeanG. (1995). Prevalence of multiple sclerosis in the region of Osona, Catalonia, northern Spain. J. Neurol. Neurosurg. Psychiatry, 58, 577–581.
14.
KotzamaniD., PanouT., MastorodemosV., TzagournissakisM., NikolakakiH., SpanakiC., and PlaitakisA. (2012). Rising incidence of multiple sclerosis in females associated with urbanization. Neurology, 78, 1728–1735.
15.
ThompsonA.J., RompaniP., DuaT., DouglasI., BattagliaM., and PorterB. (2008). WHO/MSIF: Atlas of MS: multiple sclerosis resources across the world. Mult. Scler., 14, S153–S153.
16.
LiuR., Van KaerL., La CavaA., PriceM., CampagnoloD.I., CollinsM., YoungD.A., VollmerT.L., and ShiF.D. (2006). Autoreactive T cells mediate NK cell degeneration in autoimmune disease. J. Immunol., 176, 5247–5254.
17.
HuangY.P., ChenL.S., YenM.F., FannC.Y., ChiuY.H., ChenH.H., and PanS.L. (2013). Parkinson's disease is related to an increased risk of ischemic stroke-a population-based propensity score-matched follow-up study. PLoS One, 8, e68314.
18.
AustinP.C. (2008). A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003. Stat. Med., 27, 2037–2049.
19.
NormandS.T., LandrumM.B., GuadagnoliE., AyanianJ.Z., RyanT.J., ClearyP.D., and McNeilB.J. (2001). Validating recommendations for coronary angiography following acute myocardial infarction in the elderly: a matched analysis using propensity scores. J. Clin. Epidemiol., 54, 387–398.
20.
BartanuszV., JezovaD., AlajajianB., and DigicayliogluM. (2011). The blood-spinal cord barrier: morphology and clinical implications. Ann. Neurol., 70, 194–206.
21.
HemmerB., ArchelosJ.J., and HartungH.P. (2002). New concepts in the immunopathogenesis of multiple sclerosis. Nat. Rev. Neurosci., 3, 291–301.
22.
McFarlandH.F. and MartinR. (2007). Multiple sclerosis: a complicated picture of autoimmunity. Nat. Immunol., 8, 913–919.
23.
HemmerB., NesslerS., ZhouD., KieseierB., and HartungH.P. (2006). Immunopathogenesis and immunotherapy of multiple sclerosis. Nat. Clin. Pract. Neurol., 2, 201–211.
24.
AnkenyD.P., LucinK.M., SandersV.M., McGaughyV.M., and PopovichP.G. (2006). Spinal cord injury triggers systemic autoimmunity: evidence for chronic B lymphocyte activation and lupus-like autoantibody synthesis. J. Neurochem., 99, 1073–1087.
25.
DekabanG.A. and ThawerS. (2009). Pathogenic antibodies are active participants in spinal cord injury. J. Clin. Invest., 119, 2881–2884.
26.
KilK., ZangY.C., YangD., MarkowskiJ., FuocoG.S., VendettiG.C., RiveraV.M., and ZhangJ.Z. (1999). T cell responses to myelin basic protein in patients with spinal cord injury and multiple sclerosis. J. Neuroimmunol., 98, 201–207.
27.
JonesT.B., BassoD.M., SodhiA., PanJ.Z., HartR.P., MacCallumR.C., LeeS., WhitacreC.C., and PopovichP.G. (2002). Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J. Neurosci., 22, 2690–2700.
28.
PopovichP.G., StokesB.T., and WhitacreC.C. (1996). Concept of autoimmunity following spinal cord injury: possible roles for T lymphocytes in the traumatized central nervous system. J. Neurosci. Res., 45, 349–363.
29.
MiglioriniC.E., NewP.W., and TongeB.J. (2009). Comparison of depression, anxiety and stress in persons with traumatic and non-traumatic post-acute spinal cord injury. Spinal Cord, 47, 783–788.
30.
NielsenM.S. (2003). Post-traumatic stress disorder and emotional distress in persons with spinal cord lesion. Spinal Cord, 41, 296–302.
31.
GrantI., BrownG.W., HarrisT., McDonaldW.I., PattersonT., and TrimbleM.R. (1989). Severely threatening events and marked life difficulties preceding onset or exacerbation of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry, 52, 8–13.
32.
WarrenS., GreenhillS., and WarrenK.G. (1982). Emotional stress and the development of multiple sclerosis: case-control evidence of a relationship. J. Chronic Dis., 35, 821–831.
33.
ChengC.L., KaoY.H., LinS.J., LeeC.H., and LaiM.L. (2011). Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol. Drug Saf., 20, 236–242.
34.
WenC.P., TsaiS.P., and ChungW.S. (2008). A 10-year experience with universal health insurance in Taiwan: measuring changes in health and health disparity. Ann. Intern. Med., 148, 258–267.
35.
RamagopalanS.V., DobsonR., MeierU.C., and GiovannoniG. (2010). Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol., 9, 727–739.
36.
HernanM.A., OlekM.J., and AscherioA. (2001). Cigarette smoking and incidence of multiple sclerosis. Am. J. Epidemiol., 154, 69–74.
37.
RiiseT., NortvedtM.W., and AscherioA. (2003). Smoking is a risk factor for multiple sclerosis. Neurology, 61, 1122–1124.
38.
van der MeiI.A., PonsonbyA.L., DwyerT., BlizzardL., SimmonsR., TaylorB.V., ButzkuevenH., and KilpatrickT. (2003). Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ, 327, 316.
39.
MungerK.L., ZhangS.M., O'ReillyE., HernanM.A., OlekM.J., WillettW.C., and AscherioA. (2004). Vitamin D intake and incidence of multiple sclerosis. Neurology, 62, 60–65.
