Skip to main content
SpringerLink
Log in

Autoimmune comorbidities in multiple sclerosis: what is the influence on brain volumes? A case–control MRI study

Journal of Neurology volume 265, pages 1096–1101 (2018)Cite this article

Abstract

Background

Several studies indicated that multiple sclerosis (MS) is frequently associated with other autoimmune diseases. However, it is little known if the coexistence of these conditions may influence the radiologic features of MS, and in particular the brain volumes.

Objectives

To evaluate the effect of autoimmune comorbidities on brain atrophy in a large case–control MS population.

Methods

A group of MS patients affected by a second autoimmune disorder, and a control MS group without any comorbidity, were recruited. Patients underwent a brain MRI and volumes of whole brain (WB), white matter (WM), and gray matter (GM) with cortical GM were estimated by SIENAX.

Results

The sample included 286 MS patients, of which 30 (10.5%) subjects with type 1 diabetes (T1D), 53 (18.5%) with autoimmune thyroiditis (AT) and 4 (0.1%) with celiac disease. Multiple regression analysis found an association between T1D and lower GM (p = 0.038) and cortical GM (p = 0.036) volumes, independent from MS clinical features and related to T1D duration (p < 0.01), while no association was observed with AT and celiac disease.

Conclusions

Our data support the importance of considering T1D as possible factors influencing the brain atrophy in MS. Further studies are needed to confirm our data and to clarify the underlying mechanisms.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Haider L, Zrzavy T, Hametner S et al (2016) The topography of demyelination and neurodegeneration in the multiple sclerosis brain. Brain 139(Pt 3):807–815

    Article  PubMed  PubMed Central  Google Scholar 

  2. Stinissen P, Raus J, Zhang J (1997) Autoimmune pathogenesis of multiple sclerosis: role of autoreactive T lymphocytes and new immunotherapeutic strategies. Crit Rev Immunol 17(1):33–75

    Article  CAS  PubMed  Google Scholar 

  3. Lucchinetti CF, Brück W, Rodriguez M et al (1996) Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol 6(3):259–274

    Article  CAS  PubMed  Google Scholar 

  4. Lemus HN, Warrington AE, Rodriguez M (2018) Multiple sclerosis: mechanisms of disease and strategies for myelin and axonal repair. Neurol Clin 36(1):1–11

    Article  PubMed  Google Scholar 

  5. Marrosu MG, Cocco E, Lai M et al (2002) Patients with multiple sclerosis and risk of type 1 diabetes mellitus in Sardinia, Italy: a cohort study. Lancet 359(9316):1461–1465

    Article  PubMed  Google Scholar 

  6. Tettey P, Simpson S Jr, Taylor BV et al (2015) The co-occurrence of multiple sclerosis and type 1 diabetes: shared aetiologic features and clinical implication for MS aetiology. J Neurol Sci 348(1–2):126–131

    Article  PubMed  Google Scholar 

  7. Sardu C, Cocco E, Mereu A et al (2012) Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity. PLoS ONE 7(3):e32487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Marrie RA, Reider N, Cohen J et al (2015) A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis. Mult Scler. 21(3):282–293

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ramagopalan SV, Dobson R, Meier UC et al (2010) Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol. 9(7):727–739

    Article  PubMed  Google Scholar 

  10. Steri M, Orrù V, Idda ML et al (2017) Overexpression of the cytokine BAFF and autoimmunity risk. N Engl J Med 376(17):1615–1626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Karni A, Abramsky O (1999) Association of MS with thyroid disorders. Neurology. 53(4):883–885

    Article  CAS  PubMed  Google Scholar 

  12. Dorman JS, Steenkiste AR, Burke JP, Songini M (2003) Type 1 diabetes and multiple sclerosis: together at last. Diabetes Care 26(11):3192–3193

    Article  PubMed  Google Scholar 

  13. Nielsen NM, Westergaard T, Frisch M et al (2006) Type 1 diabetes and multiple sclerosis: a Danish population-based cohort study. Arch Neurol 63:1001–1004

    Article  PubMed  Google Scholar 

  14. Hussein WI, Reddy SS (2006) Prevalence of diabetes in patients with multiple sclerosis. Diabetes Care 29:1984–1985

    Article  PubMed  Google Scholar 

  15. Lampis R, Morelli L, De Virgiliis S et al (2000) The distribution of HLA class II haplotypes reveals that the Sardinian population is genetically differentiated from the other Caucasian populations. Tissue Antigens 56(6):515–521

    Article  CAS  PubMed  Google Scholar 

  16. Kotelnikova E, Kiani NA, Abad E et al (2017) Dynamics and heterogeneity of brain damage in multiple sclerosis. PLoS Comput Biol 13(10):e1005757

    Article  PubMed  PubMed Central  Google Scholar 

  17. De Stefano N, Stromillo ML, Giorgio A et al (2016) Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis. J Neurol Neurosurg Psychiatry 87(1):93–99

    PubMed  Google Scholar 

  18. Pichler A, Khalil M, Langkammer C et al (2017) The impact of vascular risk factors on brain volume and lesion load in patients with early multiple sclerosis. Mult Scler. 1:1352458517736149

    Google Scholar 

  19. Zivadinov R, Raj B, Ramanathan M et al (2016) Autoimmune comorbidities are associated with brain injury in multiple sclerosis. AJNR Am J Neuroradiol 37(6):1010–1016

    Article  CAS  PubMed  Google Scholar 

  20. Cocco E, Sardu C, Massa R et al (2011) Epidemiology of multiple sclerosis in south-western Sardinia. Mult Scler. 17(11):1282–1289

    Article  PubMed  Google Scholar 

  21. Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33(11):1444–1452

    Article  CAS  PubMed  Google Scholar 

  23. Cendrowski WS (1986) Progression index and disability status in multiple sclerosis: a resurvey of 207 patients in central Poland. Schweiz Arch Neurol Psychiatr (1985). 137(4):5–13

    CAS  Google Scholar 

  24. Smith SM, Zhang Y, Jenkinson M et al (2002) Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage. 17(1):479–489

    Article  PubMed  Google Scholar 

  25. Sahraian MA, Owji M, Naser Moghadasi A (2016) Concomitant multiple sclerosis and another autoimmune disease: does the clinical course change? Clin Neurol Neurosurg 150:9295

    Article  Google Scholar 

  26. Giorgio A, De Stefano N (2013) Clinical use of brain volumetry. J Magn Reson Imaging 37(1):1–14

    Article  PubMed  Google Scholar 

  27. De Stefano N, Airas L, Grigoriadis N et al (2014) Clinical relevance of brain volume measures in multiple sclerosis. CNS Drugs 28:147–156

    Article  PubMed  Google Scholar 

  28. Winer S, Astsaturov I, Cheung R et al (2001) Type I diabetes and multiple sclerosis patients target islet plus central nervous system autoantigens; nonimmunized nonobese diabetic mice can develop autoimmune encephalitis. J Immunol. 166(4):2831–2841

    Article  CAS  PubMed  Google Scholar 

  29. Magliozzi R, Howell OW, Reeves C et al (2010) Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 68(4):477–493

    Article  CAS  PubMed  Google Scholar 

  30. Pell GS, Lin A, Wellard RM et al (2012) Age-related loss of brain volume and T2 relaxation time in youth with type 1 diabetes. Diabetes Care 35(3):513–519

    Article  PubMed  PubMed Central  Google Scholar 

  31. Perantie DC, Wu J, Koller JM, Lim A, Warren SL, Black KJ, Sadler M, White NH, Hershey T (2007) Regional brain volume differences associated with hyperglycemia and severe hypoglycemia in youth with type 1 diabetes. Diabetes Care 30(9):2331–2337

    Article  PubMed  Google Scholar 

  32. Jefferson AL, Massaro JM, Wolf PA et al (2007) Inflammatory biomarkers are associated with total brain volume: the Framingham Heart Study. Neurology 68:1032–1038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Marrie RA, Rudick R, Horwitz R et al (2010) Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 74:1041–1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Sciences and Public Health, Multiple Sclerosis Center, Binaghi Hospital, ATS Sardegna, University of Cagliari, via Is Guadazzonis 2, 09126, Cagliari, Italy

    Lorena Lorefice, Giuseppe Fenu, Roberta Pitzalis, Giulia Scalas, Jessica Frau, Giancarlo Coghe, Luigina Musu, Maria Giovanna Marrosu & Eleonora Cocco

  2. Radiology Unit, Binaghi Hospital, ATS Sardegna, Cagliari, Italy

    Vincenzo Sechi & Maria Antonietta Barracciu

Authors
  1. Lorena Lorefice
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppe Fenu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberta Pitzalis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giulia Scalas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jessica Frau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giancarlo Coghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luigina Musu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vincenzo Sechi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maria Antonietta Barracciu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maria Giovanna Marrosu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Eleonora Cocco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lorena Lorefice.

Ethics declarations

Conflicts of interest

Dr. Lorefice has received speaker fees from Teva and serves on scientific advisory boards for Biogen. Dr. Fenu has received honoraria for consultancy from Novartis and for speaking from Merck Serono and Teva. Dr. Frau serves on scientific advisory boards for Biogen, and has received honoraria for speaking from Merck Serono and Teva. Dr. Coghe has received speaker fees from Teva and Almirall. Professors Cocco and Marrosu have received honoraria for consultancy or speaking from Bayer, Biogen, Novartis, Sanofi, Genzyme, Serono, and Teva. Dr. Barracciu, Dr. Musu, Dr. Pitzalis, Dr. Sechi, and Dr. Scalas have nothing to disclose.

Ethical standards

The study was performed in accordance with the ethical standards statement.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 34 kb)

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lorefice, L., Fenu, G., Pitzalis, R. et al. Autoimmune comorbidities in multiple sclerosis: what is the influence on brain volumes? A case–control MRI study. J Neurol 265, 1096–1101 (2018). https://doi.org/10.1007/s00415-018-8811-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-018-8811-1

Keywords

search

Navigation