Document Type : Original Article


1 Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

2 Bam University of Medical Sciences, Bam, Iran


Background: The association betweenmedical history and primary progressive multiple sclerosis (PPMS) development has not been well documented in the pertinent literature.The possible association between 23 medical diseases and PPMS occurrence was assessed in the present study.
Methods: In order to figure out the possible association between several medical histories and PPMS occurrence, the present population-based case-control study examined 143 PPMS cases in Tehran, Iran, from 2019 to 2020. Diagnosis of PPMS was confirmed by neurologists based on the 2017 McDonald criteria. Sex-matched healthy controls (n = 143) were selected using the random-digit dialing (RDD) technique. Face-to-face and telephone interviews were conducted for gathering the data. The conditional logistic regression model was used to calculate adjusted and unadjusted odds ratio (OR) at a 95% confidence interval (CI).
Results: A significant association was found between PPMS development and diseases like depression (OR = 3.12, 95% CI: 1.49-6.53), migraine (OR = 0.19, 95% CI: 0.05-0.67), infectious mononucleosis (OR = 13.16, 95% CI: 2.74-63.17), hypothyroidism (OR = 3.20, 95% CI: 1.23-8.30), and kidney failure (OR = 3.76, 95% CI: 1.41-9.99).
Conclusion: Lifetime history of depression, infectious mononucleosis, hypothyroidism, and kidney failure might increase the risk of PPMS development, while individuals with positive history of migraine disease are at lower risk for developing PPMS.


  1. Global, regional, and national burden of neurological disorders, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18(5): 459-80.
  2. Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, et al. Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity. Neurology 2014; 83(11): 1022-4.
  3. Azami M, YektaKooshali MH, Shohani M, Khorshidi A, Mahmudi L. Epidemiology of multiple sclerosis in Iran: A systematic review and meta-analysis. PLoS One 2019; 14(4): e0214738.
  4. Lublin FD. New multiple sclerosis phenotypic classification. Eur Neurol 2014; 72(Suppl 1): 1-5.
  5. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology 2014; 83(3): 278-86.
  6. Kantarci OH. Phases and phenotypes of multiple sclerosis. Continuum (Minneap Minn) 2019; 25(3): 636-54.
  7. Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I. Environmental risk factors and multiple sclerosis: An umbrella review of systematic reviews and meta-analyses. Lancet Neurol 2015; 14(3): 263-73.
  8. McKay KA, Kwan V, Duggan T, Tremlett H. Risk factors associated with the onset of relapsing-remitting and primary progressive multiple sclerosis: A systematic review. Biomed Res Int 2015; 2015: 817238.
  9. Waubant E, Lucas R, Mowry E, Graves J, Olsson T, Alfredsson L, et al. Environmental and genetic risk factors for MS: An integrated review. Ann Clin Transl Neurol 2019; 6(9): 1905-22.
  10. Tremlett H, Zhu F, Ascherio A, Munger KL. Sun exposure over the life course and associations with multiple sclerosis. Neurology 2018; 90(14): e1191-e1199.
  11. Tremlett H, Zhao Y, Devonshire V. Natural history comparisons of primary and secondary progressive multiple sclerosis reveals differences and similarities. J Neurol 2009; 256(3): 374-81.
  12. Koch M, Kingwell E, Rieckmann P, Tremlett H. The natural history of primary progressive multiple sclerosis. Neurology 2009; 73(23): 1996-2002.
  13. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17(2): 162-73.
  14. Eskandarieh S, Nedjat S, Abdollahpour I, Azimi AR, Moghadasi AN, Asgari N, et al. Environmental risk factors in neuromyelitis optica spectrum disorder: A case-control study. Acta Neurol Belg 2018; 118(2): 277-87.
  15. Clagett B, Nathanson KL, Ciosek SL, McDermoth M, Vaughn DJ, Mitra N, et al. Comparison of address-based sampling and random-digit dialing methods for recruiting young men as controls in a case-control study of testicular cancer susceptibility. Am J Epidemiol 2013; 178(11): 1638-47.
  16. Pugliatti M, Casetta I, Drulovic J, Granieri E, Holmoy T, Kampman MT, et al. A questionnaire for multinational case-control studies of environmental risk factors in multiple sclerosis (EnvIMS-Q). Acta Neurol Scand Suppl 2012; (195): 43-50.
  17. Sahraian MA, Naghshineh H, Shati M, Jahromi SR, Rezaei N. Persian adaptation of a questionnaire of environmental risk factors in multiple sclerosis (EnvIMS-Q). Mult Scler Relat Disord 2016; 10: 82-5.
  18. Abdollahpour I, Nedjat S, Mansournia MA, Sahraian MA, Asgari N. Parental ethnicity associated with risk for multiple sclerosis: A population-based incident case-control study in Iran. Mult Scler Relat Disord 2018; 20: 100-3.
  19. Feinstein A. Multiple sclerosis and depression. Mult Scler 2011; 17(11): 1276-81.
  20. Patten SB, Beck CA, Williams JV, Barbui C, Metz LM. Major depression in multiple sclerosis: A population-based perspective. Neurology 2003; 61(11): 1524-7.
  21. Abdollahpour I, Lizarraga AA, Nedjat S, Mansournia MA, Weinstock-Guttman B. Medical history and multiple sclerosis: A population-based incident case-control study. Neuroepidemiology 2019; 52(1-2): 55-62.
  22. Ahlgren C, Oden A, Bergstrom T, Lycke J. Serum and CSF measles antibody levels increase over time in patients with multiple sclerosis or clinically isolated syndrome. J Neuroimmunol 2012; 247(1-2): 70-4.
  23. Abbasi M, Nabavi SM, Fereshtehnejad SM, Jou NZ, Ansari I, Shayegannejad V, et al. Multiple sclerosis and environmental risk factors: A case-control study in Iran. Neurol Sci 2017; 38(11): 1941-51.
  24. Ahlgren C, Oden A, Toren K, Andersen O. Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations. Acta Neurol Scand 2009; 119(5): 313-20.
  25. Pakpoor J, Handel AE, Giovannoni G, Dobson R, Ramagopalan SV. Meta-analysis of the relationship between multiple sclerosis and migraine. PLoS One 2012; 7(9): e45295.
  26. Gee JR, Chang J, Dublin AB, Vijayan N. The association of brainstem lesions with migraine-like headache: An imaging study of multiple sclerosis. Headache 2005; 45(6): 670-7.
  27. Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H, et al. Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 2004; 113(10): 1447-55.
  28. Jacobs BM, Giovannoni G, Cuzick J, Dobson R. Systematic review and meta-analysis of the association between Epstein-Barr virus, multiple sclerosis and other risk factors. Mult Scler 2020; 26(11): 1281-97.
  29. Nielsen NM, Frisch M, Rostgaard K, Wohlfahrt J, Hjalgrim H, Koch-Henriksen N, et al. Autoimmune diseases in patients with multiple sclerosis and their first-degree relatives: A nationwide cohort study in Denmark. Mult Scler 2008; 14(6): 823-9.
  30. Marrie RA, Reider N, Cohen J, Stuve O, Sorensen PS, Cutter G, et al. A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis. Mult Scler 2015; 21(3): 282-93.
  31. Cossburn M, Pace AA, Jones J, Ali R, Ingram G, Baker K, et al. Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology 2011; 77(6): 573-9.
  32. Costelloe L, Jones J, Coles A. Secondary autoimmune diseases following alemtuzumab therapy for multiple sclerosis. Expert Rev Neurother 2012; 12(3): 335-41.
  33. McCombe PA, Gordon TP, Jackson MW. Bladder dysfunction in multiple sclerosis. Expert Rev Neurother 2009; 9(3): 331-40.
  34. Ganesan V, Chen WM, Jain R, De S, Monga M. Multiple sclerosis and nephrolithiasis: A matched-case comparative study. BJU Int 2017; 119(6): 919-25.
  35. Hertzberg D, Ryden L, Pickering JW, Sartipy U, Holzmann MJ. Acute kidney injury-an overview of diagnostic methods and clinical management. Clin Kidney J 2017; 10(3): 323-31.
  36. Storme O, Tiran Saucedo J., Garcia-Mora A, Dehesa-Davila M, Naber KG. Risk factors and predisposing conditions for urinary tract infection. Ther Adv Urol 2019; 11: 1756287218814382.
  37. Shakir NA, Satyanarayan A, Eastman J, Greenberg BM, Lemack GE. Assessment of renal deterioration and associated risk factors in patients with multiple sclerosis. Urology 2019; 123: 76-80.
  38. Fletcher SG, Dillon BE, Gilchrist AS, Haverkorn RM, Yan J, Frohman EM, et al. Renal deterioration in multiple sclerosis patients with neurovesical dysfunction. Mult Scler 2013; 19(9): 1169-74.
  39. Giannantoni A, Scivoletto G, Di Stasi SM, Grasso MG, Vespasiani G, Castellano V. Urological dysfunctions and upper urinary tract involvement in multiple sclerosis patients. Neurourol Urodyn 1998; 17(2): 89-98.
  40. Betts CD, D'Mellow MT, Fowler CJ. Urinary symptoms and the neurological features of bladder dysfunction in multiple sclerosis. J Neurol Neurosurg Psychiatry 1993; 56(3): 245-50.
  41. Montgomery S, Hiyoshi A, Burkill S, Alfredsson L, Bahmanyar S, Olsson T. Concussion in adolescence and risk of multiple sclerosis. Ann Neurol 2017; 82(4): 554-61.