Determinants of Disability in Multiple Sclerosis: an Immunological and MRI Study

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2014 May 13

PMID 24818159

Citations 6

Authors

Paola Tortorella

Maria Marcella Lagana

Marina Saresella

Eleonora Tavazzi

Maria Giulia Preti

Cristian Ricci

Francesca Baglio

Ivana Marventano

Federica Piancone

Giuseppe Baselli

Pietro Cecconi

Domenico Caputo

Mario Clerici

Marco Rovaris

Affiliations

Soon will be listed here.

Abstract

Multiple sclerosis (MS) is characterized by a wide interpatient clinical variability and available biomarkers of disease severity still have suboptimal reliability. We aimed to assess immunological and MRI-derived measures of brain tissue damage in patients with different motor impairment degrees, for in vivo investigating the pathogenesis of MS-related disability. Twenty-two benign (B), 26 secondary progressive (SP), and 11 early, nondisabled relapsing-remitting (RR) MS patients and 37 healthy controls (HC) underwent conventional and diffusion tensor brain MRI and, as regards MS patients, immunophenotypic and functional analysis of stimulated peripheral blood mononuclear cells (PBMC). Corticospinal tract (CST) fractional anisotropy and grey matter volume were lower and CST diffusivity was higher in SPMS compared to RRMS and BMS patients. CD14+IL6+ and CD4+IL25+ cell percentages were higher in BMS than in SPMS patients. A multivariable model having EDSS as the dependent variable retained the following independent predictors: grey matter volume, CD14+IL6+ and CD4+IL25+ cell percentages. In patients without motor impairment after long-lasting MS, the grey matter and CST damage degree seem to remain as low as in the earlier disease stages and an immunological pattern suggestive of balanced pro- and anti-inflammatory activity is observed. MRI-derived and immunological measures might be used as complementary biomarkers of MS severity.

Citing Articles

Palliative care needs of patients with multiple sclerosis in southeast Iran.

Dadsetan F, Shahrbabaki P, Mirzai M, Nouhi E BMC Palliat Care. 2021; 20(1):169.

PMID: 34706707 PMC: 8554857. DOI: 10.1186/s12904-021-00867-3.

The impairment of the functional system and fatigue at the onset of the disease predict reaching disability milestones in relapsing-remitting multiple sclerosis differently in female and male patients.

Ivaniuk A, Solodovnikova Y, Marusich T, Son A Acta Neurol Belg. 2020; 121(6):1699-1706.

PMID: 32997326 DOI: 10.1007/s13760-020-01478-0.

Immunopathological Factors Associated with Disability in Multiple Sclerosis.

Tuzun E Noro Psikiyatr Ars. 2019; 55(Suppl 1):S26-S30.

PMID: 30692851 PMC: 6278616. DOI: 10.29399/npa.23303.

Diffusion tensor imaging and disability progression in multiple sclerosis: A 4-year follow-up study.

Kolasa M, Hakulinen U, Brander A, Hagman S, Dastidar P, Elovaara I Brain Behav. 2018; 9(1):e01194.

PMID: 30588771 PMC: 6346728. DOI: 10.1002/brb3.1194.

Serum lipid antibodies are associated with cerebral tissue damage in multiple sclerosis.

Bakshi R, Yeste A, Patel B, Tauhid S, Tummala S, Rahbari R Neurol Neuroimmunol Neuroinflamm. 2016; 3(2):e200.

PMID: 26894204 PMC: 4747479. DOI: 10.1212/NXI.0000000000000200.

References

Smith S, De Stefano N, Jenkinson M, Matthews P . Normalized accurate measurement of longitudinal brain change. J Comput Assist Tomogr. 2001; 25(3):466-75. DOI: 10.1097/00004728-200105000-00022. View

La Mantia L, Vacchi L, Rovaris M, Di Pietrantonj C, Ebers G, Fredrikson S . Interferon β for secondary progressive multiple sclerosis: a systematic review. J Neurol Neurosurg Psychiatry. 2012; 84(4):420-6. DOI: 10.1136/jnnp-2012-303291. View

Reich D, Ozturk A, Calabresi P, Mori S . Automated vs. conventional tractography in multiple sclerosis: variability and correlation with disability. Neuroimage. 2009; 49(4):3047-56. PMC: 2843834. DOI: 10.1016/j.neuroimage.2009.11.043. View

Lagana M, Ceccarelli A, Preti M, Venturelli C, Sormani M, Cavarretta R . Atlas-based versus individual-based fiber tracking of the corpus callosum in patients with multiple sclerosis: reliability and clinical correlations. J Neuroimaging. 2011; 22(4):355-64. DOI: 10.1111/j.1552-6569.2011.00650.x. View

Gauthier S, Berger A, Liptak Z, Duan Y, Egorova S, Buckle G . Rate of brain atrophy in benign vs early multiple sclerosis. Arch Neurol. 2009; 66(2):234-7. DOI: 10.1001/archneurol.2008.567. View

Calabrese M, Poretto V, Favaretto A, Alessio S, Bernardi V, Romualdi C . Cortical lesion load associates with progression of disability in multiple sclerosis. Brain. 2012; 135(Pt 10):2952-61. DOI: 10.1093/brain/aws246. View

Bergsland N, Horakova D, Dwyer M, Dolezal O, Seidl Z, Vaneckova M . Subcortical and cortical gray matter atrophy in a large sample of patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol. 2012; 33(8):1573-8. PMC: 7966546. DOI: 10.3174/ajnr.A3086. View

Tubridy N, Coles A, Molyneux P, Compston D, Barkhof F, Thompson A . Secondary progressive multiple sclerosis: the relationship between short-term MRI activity and clinical features. Brain. 1998; 121 ( Pt 2):225-31. DOI: 10.1093/brain/121.2.225. View

Kremenchutzky M, Rice G, Baskerville J, Wingerchuk D, Ebers G . The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain. 2006; 129(Pt 3):584-94. DOI: 10.1093/brain/awh721. View

10.

Spano B, Cercignani M, Basile B, Romano S, Mannu R, Centonze D . Multiparametric MR investigation of the motor pyramidal system in patients with 'truly benign' multiple sclerosis. Mult Scler. 2009; 16(2):178-88. DOI: 10.1177/1352458509356010. View

11.

Saresella M, Calabrese E, Marventano I, Piancone F, Gatti A, Alberoni M . Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer's disease. Brain Behav Immun. 2010; 25(3):539-47. DOI: 10.1016/j.bbi.2010.12.004. View

12.

Hackmack K, Weygandt M, Wuerfel J, Pfueller C, Bellmann-Strobl J, Paul F . Can we overcome the 'clinico-radiological paradox' in multiple sclerosis?. J Neurol. 2012; 259(10):2151-60. DOI: 10.1007/s00415-012-6475-9. View

13.

Rovaris M, Barkhof F, Calabrese M, De Stefano N, Fazekas F, Miller D . MRI features of benign multiple sclerosis: toward a new definition of this disease phenotype. Neurology. 2009; 72(19):1693-701. DOI: 10.1212/WNL.0b013e3181a55feb. View

14.

Polman C, Reingold S, Edan G, Filippi M, Hartung H, Kappos L . Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005; 58(6):840-6. DOI: 10.1002/ana.20703. View

15.

Penkowa M, Moos T, Carrasco J, Hadberg H, Molinero A, Bluethmann H . Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice. Glia. 1999; 25(4):343-57. View

16.

Magliozzi R, Howell O, Vora A, Serafini B, Nicholas R, Puopolo M . Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain. 2007; 130(Pt 4):1089-104. DOI: 10.1093/brain/awm038. View

17.

Saresella M, Piancone F, Tortorella P, Marventano I, Gatti A, Caputo D . T helper-17 activation dominates the immunologic milieu of both amyotrophic lateral sclerosis and progressive multiple sclerosis. Clin Immunol. 2013; 148(1):79-88. DOI: 10.1016/j.clim.2013.04.010. View

18.

Lublin F, Reingold S . Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996; 46(4):907-11. DOI: 10.1212/wnl.46.4.907. View

19.

Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F . Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol. 2004; 14(2):164-74. PMC: 8095922. DOI: 10.1111/j.1750-3639.2004.tb00049.x. View

20.

Saresella M, Marventano I, Guerini F, Zanzottera M, Delbue S, Marchioni E . Myelin basic protein-specific T lymphocytes proliferation and programmed cell death in demyelinating diseases. Clin Immunol. 2008; 129(3):509-17. PMC: 2597154. DOI: 10.1016/j.clim.2008.08.010. View