The art of brain preservation in multiple sclerosis

Examining the Data on Multiple Sclerosis

Source Materials Organized by Topic

MS Mechanism of Disease

Duffy SS, Lees JG, Moalem-Taylor G. The contribution of immune and glial cell types in experimental autoimmune encephalomyelitis and multiple sclerosis. Mult Scler Int. 2014;2014:1-17. doi:10.1155/2014/285245

Krieger SC, Cook K, De Nino S, Fletcher M. The topographical model of multiple sclerosis: a dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e279.

Mechanism of MS–Role of Glial Cells

Duffy SS, Lees JG, Moalem-Taylor G. The contribution of immune and glial cell types in experimental autoimmune encephalomyelitis and multiple sclerosis. Mult Scler Int. 2014;2014:1-17. doi:10.1155/2014/285245

Høglund RA, Maghazachi AA. Multiple sclerosis and the role of immune cells. World J Exp Med. 2014;4(3):27-37.

Krieger SC, Cook K, De Nino S, Fletcher M. The topographical model of multiple sclerosis: a dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e279.

Luo C, Jian C, Liao Y, et al. The role of microglia in multiple sclerosis. Neuropsychiatr Dis Treat. 2017;13:1661-1667.

Markiewicz I, Lukomska B. The role of astrocytes in the physiology and pathology of the central nervous system. Acta Neurobiol Exp (Wars). 2006;66(4):343-358.

Merson TD, Binder MD, Kilpatrick TJ. Role of cytokines as mediators and regulators of microglial activity in inflammatory demyelination of the CNS. Neuromolecular Med. 2010;12(2):99-132.

Nair A, Frederick TJ, Miller SD. Astrocytes in multiple sclerosis: a product of their environment. Cell Mol Life Sci. 2008;65(17):2702-2720.

Prinz M, Priller J. The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci. 2017;20(2):136-144.

van der Walt A, Butzkueven H, Kolbe S, et al. Neuroprotection in multiple sclerosis: a therapeutic challenge for the next decade. Pharmacol Ther. 2010;126(1):82-93.

Weiner HL. A shift from adaptive to innate immunity: a potential mechanism of disease progression in multiple sclerosis. J Neurol. 2008;255(suppl 1):3-11.

Mechanism of MS–Migration/Activation

Aoki M, Aoki H, Ramanathan R, Hait NC, Takabe K. Sphingosine-1-phosphate signaling in immune cells and inflammation: roles and therapeutic potential. Mediators Inflamm. 2016;2016:8606878. doi:10.1155/2016/8606878

Baeyens A, Fang V, Chen C, Schwab SR. Exit strategies: S1P signaling and T cell migration. Trends Immunol. 2015;36(12):778-787.

Blaho VA, Hla T. An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res. 2014;55(8):1596-1608.

Cannavo A, Liccardo D, Komici K, et al. Sphingosine kinases and sphingosine 1-phosphate receptors: signaling and actions in the cardiovascular system. Front Pharmacol. 2017;8:1-12. doi:10.3389/fphar.2017.00556

Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545-558.

Ishii I, Fukushima N, Ye X, Chun J. Lysophospholipid receptors: signaling and biology. Annu Rev Biochem. 2004;73:321-354.

Li N, Zhang F. Implication of sphingosin-1-phosphate in cardiovascular regulation. Front Biosci (Landmark Ed). 2016;21:1296-1313.

Ohmori T, Yatomi Y, Osada M, et al. Sphingosine 1-phosphate induces contraction of coronary artery smooth muscle cells via S1P2. Cardiovasc Res. 2003;58(1):170-177.

Prinz M, Priller J. The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci. 2017;20(2):136-144.

Proia RL, Hla T. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest. 2015;125(4):1379-1387.

Sanna MG, Vincent KP, Repetto E, et al. Bitopic sphingosine 1-phosphate receptor 3 (S1P3) antagonist rescue from complete heart block: pharmacological and genetic evidence for direct S1P3 regulation of mouse cardiac conduction. Mol Pharmacol. 2016;89(1):176-186.

Schwab SR, Cyster JG. Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol. 2007;8:1295-1301.

Early Damage–Neurological Reserve

Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016;9(suppl 1):S5-S48.

Early Damage–White Matter

Calabrese M, Magliozzi R, Ciccarelli O, Geurts JJG, Reynolds R, Martin R. Exploring the origins of grey matter damage in multiple sclerosis. Nat Rev Neurosci. 2015;16(3):147-158.

Popescu BFG, Pirko I, Lucchinetti CF. Pathology of multiple sclerosis: where do we stand? Continuum (Minneap Minn). 2013;19(4):901-921.

Early Damage–Grey Matter Atrophy

Azevedo CJ, Cen SY, Khadka S, et al. Thalamic atrophy in multiple sclerosis: a magnetic resonance imaging marker of neurodegeneration throughout disease. Ann Neurol. 2018;83(2):223-234.

Calabrese M, Rinaldi F, Grossi P, Gallo P. Cortical pathology and cognitive impairment in multiple sclerosis. Expert Rev Neurother. 2011;11(3):425-432.

Chard DT, Griffin CM, Rashid W, et al. Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler. 2004;10(4):387-391.

Dalton CM, Chard DT, Davies GR, et al. Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain. 2004;127(5):1101-1107.

Fisher E, Lee J-C, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008;64(3):255-265.

Minagar A, Barnett MH, Benedict RHB, et al. The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects. Neurology. 2013;80(2):210-219.

Steenwijk MD, Daams M, Pouwels PJW, et al. What explains gray matter atrophy in long-standing multiple sclerosis? Radiology. 2014;272(3):832-842.

Tiberio M, Chard DT, Altmann DR, et al. Gray and white matter volume changes in early RRMS: a 2-year longitudinal study. Neurology. 2005;64(6):1001-1007.

Early Damage–Grey Matter Lesions

Calabrese M, Rocca MA, Atzori M, et al. A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosis. Ann Neurol. 2010;67(3):376-383.

Calabrese M, Magliozzi R, Ciccarelli O, Geurts JJG, Reynolds R, Martin R. Exploring the origins of grey matter damage in multiple sclerosis. Nat Rev Neurosci. 2015;16(3):147-158.

Grey Matter Pathology–Overview

Calabrese M, Rinaldi F, Grossi P, Gallo P. Cortical pathology and cognitive impairment in multiple sclerosis. Expert Rev Neurother. 2011;11(3):425-432.

Crespy L, Zaaraoui W, Lemaire M, et al. Prevalence of grey matter pathology in early multiple sclerosis assessed by magnetization transfer ratio imaging. PLoS One. 2011;6(9):1-6. doi:10.1371/journal.pone.0024969

Enzinger C, Fazekas F. Measuring gray matter and white matter damage in MS: why this is not enough. Front Neurol. 2015:6(56):1-4. doi:10.3389/fneur.2015.00056

Fisher E, Lee J-C, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008;64(3):255-265.

Geurts JJG, Calabrese M, Fisher E, Rudick RA. Measurement and clinical effect of grey matter pathology in multiple sclerosis. Lancet Neurol. 2012;11(12):1082-1092.

Hulst HE, Geurts JJG. Gray matter imaging in multiple sclerosis: what have we learned? BMC Neurol. 2011;11:1-11. doi:10.1186/1471-2377-11-153

Minagar A, Barnett MH, Benedict RHB, et al. The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects. Neurology. 2013;80(2):210-219.

Popescu BFG, Pirko I, Lucchinetti CF. Pathology of multiple sclerosis: where do we stand? Continuum (Minneap Minn). 2013;19(4):901-921.

van de Pavert SHP, Muhlert N, Sethi V, et al. DIR-visible grey matter lesions and atrophy in multiple sclerosis: partners in crime? J Neurol Neurosurg Psychiatry. 2015;87(5):461-467.

Impact of Grey Matter Atrophy

Achiron A, Barak Y. Cognitive impairment in probable multiple sclerosis. J Neurol Neurosurg Psychiatry. 2003;74(4):443-446. doi:10.1136/jnnp.74.4.443

Bergsland N, Horakova D, Dwyer MG, et al. Gray matter atrophy patterns in multiple sclerosis: a 10-year source-based morphometry study. Neuroimage Clin. 2018;17:444-451.

Calabrese M, Rocca MA, Atzori M, et al. A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosis. Ann Neurol. 2010;67(3):376-383.

Calabrese M, Poretto V, Favaretto A, et al. Cortical lesion load associates with progression of disability in multiple sclerosis. Brain. 2012;135(10):2952-2961.

Costello K, Halper J, Kalb R, Skutnik L, Rapp R; Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Published July 2014. Updated September 2018. Accessed February 19, 2019.

Enzinger C, Fazekas F. Measuring gray matter and white matter damage in MS: why this is not enough. Front Neurol. 2015:6(56):1-4. doi:10.3389/fneur.2015.00056

Eshaghi A, Prados F, Brownlee WJ, et al; on behalf of the MAGNIMS study group. Deep gray matter volume loss drives disability worsening in multiple sclerosis. Ann Neurol. 2018;83(2):210-222.

Fisher E, Lee J-C, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008;64(3):255-265.

Fisniku LK, Chard DT, Jackson JS, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64(3):247-254.

Geurts JJG, Calabrese M, Fisher E, Rudick RA. Measurement and clinical effect of grey matter pathology in multiple sclerosis. Lancet Neurol. 2012;11(12):1082-1092.

Hulst HE, Geurts JJG. Gray matter imaging in multiple sclerosis: what have we learned? BMC Neurol. 2011;11:1-11. doi:10.1186/1471-2377-11-153

Jakimovski D, Weinstock-Guttman B, Hagemeier J, et al. Walking disability measures in multiple sclerosis patients: correlations with MRI-derived global and microstructural damage. J Neurol Sci. 2018;393:128-134.

Khan F, Amatya B, Galea M. Management of fatigue in person with multiple sclerosis. Front Neurol. 2014;5:1-15. doi:10.3389/fneur.2014.00177

Niepel G, Tench CR, Morgan PS, Evangelou N, Auer DP, Constantinescu CS. Deep gray matter and fatigue in MS: a T1 relaxation time study. J Neurol. 2006;253(7):896-902.

Roosendaal SD, Bendfeldt K, Vrenken H, et al. Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability. Mult Scler. 2011;17(9):1098-1106.

Schlaeger R, Papinutto N, Panara V, et al. Spinal cord gray matter atrophy correlates with multiple sclerosis disability. Ann Neurol. 2014;76(4):568-580.

van de Pavert SHP, Muhlert N, Sethi V, et al. DIR-visible grey matter lesions and atrophy in multiple sclerosis: partners in crime? J Neurol Neurosurg Psychiatry. 2015;87(5):461-467.

Impact of Grey Matter Lesions

Calabrese M, Rocca MA, Atzori M, et al. A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosis. Ann Neurol. 2010;67(3):376-383.

Calabrese M, Poretto V, Favaretto A, et al. Cortical lesion load associates with progression of disability in multiple sclerosis. Brain. 2012;135(10):2952-2961.

Independence of Grey Matter Pathology

Bendfeldt K, Blumhagen JO, Egger H, et al. Spatiotemporal distribution pattern of white matter lesion volumes and their association with regional grey matter volume reductions in relapsing-remitting multiple sclerosis. Hum Brain Mapp. 2010;31(10):1542-1555.

Bö L, Geurts JJG, van der Valk P, Polman C, Barkhof F. Lack of correlation between cortical demyelination and white matter pathologic changes in multiple sclerosis. Arch Neurol. 2007;64(1):76-80.

Calabrese M, Magliozzi R, Ciccarelli O, Geurts JJG, Reynolds R, Martin R. Exploring the origins of grey matter damage in multiple sclerosis. Nat Rev Neurosci. 2015;16(3):147-158.

Geurts JJG, Barkhof F. Grey matter pathology in multiple sclerosis. Lancet Neurol. 2008;7(9):841-851.

Comorbidities/Lifestyle–Overview

Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016;9(suppl 1):S5-S48.

Kowalec K, McKay KA, Patten SB, et al; for the CIHR Team in Epidemiology and Impact of Comorbidity on Multiple Sclerosis (ECoMS). Comorbidity increases the risk of relapse in multiple sclerosis: a prospective study. Neurology. 2017;89(24):2455-2461.

Marrie RA, Rudick R, Horwitz R, et al. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology. 2010;74(13):1041-1047.

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

Comorbidities–Prevalence

Kowalec K, McKay KA, Patten SB, et al; for the CIHR Team in Epidemiology and Impact of Comorbidity on Multiple Sclerosis (ECoMS). Comorbidity increases the risk of relapse in multiple sclerosis: a prospective study. Neurology. 2017;89(24):2455-2461.

Marrie RA. Comorbidity in multiple sclerosis: implications for patient care. Nat Rev Neurol. 2017;13(6):375-382.

Marrie RA, Patten SB, Tremlett H, et al; for the CIHR team in the Epidemiology and Impact of Comorbidity of Multiple Sclerosis. Sex differences in comorbidity at diagnosis of multiple sclerosis: a population-based study. Neurology. 2016;86(14):1279-1286.

Zhang T, Tremlett H, Zhu F, et al; for the CIHR Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis. Effects of physical comorbidities on disability progression in multiple sclerosis. Neurology. 2018;90(5):e419-e427.

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

Comorbidities–Impact

Coyle PK. Symptom management and lifestyle modifications in multiple sclerosis. Continuum (Minneap Minn). 2016;22(3):815-836.

Kappus N, Weinstock-Guttman B, Hagemeier J, et al. Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016;87(2):181-187.

Kowalec K, McKay KA, Patten SB, et al; for the CIHR Team in Epidemiology and Impact of Comorbidity on Multiple Sclerosis (ECoMS). Comorbidity increases the risk of relapse in multiple sclerosis: a prospective study. Neurology. 2017;89(24):2455-2461.

Weinstock-Guttman B, Zivadinov R, Mahfooz N, et al. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. J Neuroinflammation. 2011;8:1-7. doi:10.1186/1742-2094-8-127

Zhang T, Tremlett H, Zhu F, et al; for the CIHR Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis. Effects of physical comorbidities on disability progression in multiple sclerosis. Neurology. 2018;90(5):e419-e427.

Zivadinov R, Weinstock-Guttman B, Hashmi K, et al. Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis. Neurology. 2009;73(7):504-510.

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

Lifestyle Changes

Braley TJ, Kratz AL, Kaplish N, Chervin RD. Sleep and cognitive function in multiple sclerosis. Sleep. 2016;39(8):1525-1533.

Chiaravalloti ND, Moore NB, Nikelshpur OM, DeLuca J. An RCT to treat learning impairment in multiple sclerosis: the MEMREHAB trial. Neurology. 2013;81(24):2066-2072.

Chiaravalloti ND, Genova HM, DeLuca J. Cognitive rehabilitation in multiple sclerosis: the role of plasticity. Front Neurol. 2015;6:1-10. doi:10.3389/fneur.2015.00067

Coyle PK. Symptom management and lifestyle modifications in multiple sclerosis. Continuum (Minneap Minn). 2016;22(3):815-836.

Darwish H, Haddad R, Osman S, et al. Effect of vitamin D replacement on cognition in multiple sclerosis patients. Sci Rep. 2017;7:1-9. doi:10.1038/srep45926

Fitzgerald KC, Tyry T, Salter A, et al. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology. 2018;90(1):e1-e11.

Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016;9(suppl 1):S5-S48.

Kappus N, Weinstock-Guttman B, Hagemeier J, et al. Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016;87(2):181-187.

Levin AB, Hadgkiss EJ, Weiland TJ, Jelinek GA. Meditation as an adjunct to the management of multiple sclerosis. Neurol Res Int. 2014:1-10. doi:10.1155/2014/704691

Moss BP, Rensel MR, Hersh CM. Wellness and the role of comorbidities in multiple sclerosis. Neurotherapeutics. 2017;14(4):999-1017.

Motl RW, Pilutti LA, Hubbard EA, Wetter NC, Sosnoff JJ, Sutton BP. Cardiorespiratory fitness and its association with thalamic, hippocampal, and basal ganglia volumes in multiple sclerosis. Neuroimage Clin. 2015;7:661-666.

Özcan ME, İnce B, Bingöl A, et al. Association between smoking and cognitive impairment in multiple sclerosis. Neuropsychiatr Dis Treat. 2014;10:1715-1719.

Simpson R, Booth J, Lawrence M, Byrne S, Mair F, Mercer S. Mindfulness based interventions in multiple sclerosis - a systematic review. BMC Neurol. 2014;14:1-9. doi:10.1186/1471-2377-14-15

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