Top

Journal of Neurology

Published in:

01-08-2020 | Multiple Sclerosis | Original Communication

Predicting onset of secondary-progressive multiple sclerosis using genetic and non-genetic factors

Authors: Elina Misicka, Corriene Sept, Farren B. S. Briggs

Published in: Journal of Neurology | Issue 8/2020

Abstract

Background

Predicting the transition from relapsing–remitting (RR) to secondary-progressive (SP) multiple sclerosis (MS) from early in the disease course is challenging.

Objective

To construct prediction models for SPMS using sociodemographic and self-reported clinical measures that would be available at/near MS onset, with specific considerations for MS genetic risk factors.

Methods

We conducted a retrospective cross-sectional study based on 1295 white, non-Hispanic individuals. Cox proportional hazard prediction models were generated for three censored SPMS outcomes (ever transitioning, transitioning within 10 years, and transitioning within 20 years) using sociodemographic, comorbid health information, symptomatology, and other measures of early disease activity. HLADRB1*15:01 and HLA-A*02:01, as well as a genetic risk score, were iteratively considered in each model. We also explored the relationships for all 200 MS risk variants located outside the major histocompatibility complex. Nomograms were generated for the final prediction models.

Results

An older age of MS onset and being male predicted a short latency to SPMS, while a longer interval between the first two relapses predicted a much longer latency. Comorbid conditions and onset symptomatology variably predicted the risk for transitioning to SPMS for each censored outcome. The most notable observation was that HLA-A*02:01, which confers decreased risk for MS, also contributed to decreased hazards for SPMS.

Conclusions

These results have the potential to advance prognostication for a person with MS using information available at or near onset, potentially improving care and quality of life for those who live with MS.

Available only for authorised users

Wallin MT, Culpepper WJ, Campbell JD, Nelson LM, Langer-Gould A, Marrie RA, Cutter GR, Kaye WE, Wagner L, Tremlett H, Buka SL, Dilokthornsakul P, Topol B, Chen LH, LaRocca NG, Workgroup USMSP (2019) The prevalence of MS in the United States: a population-based estimate using health claims data. Neurology 92(10):e1029–e1040. https://doi.org/10.1212/WNL.0000000000007035 CrossRefPubMedPubMedCentral

Briggs FB, Hill E (2019) Estimating the prevalence of multiple sclerosis using 56.6 million electronic health records from the United States. Mult Scler. https://doi.org/10.1177/1352458519864681 CrossRefPubMed

Karabudak R, Dahdaleh M, Aljumah M, Alroughani R, Alsharoqi IA, AlTahan AM, Bohlega SA, Daif A, Deleu D, Amous A, Inshasi JS, Rieckmann P, Sahraian MA, Yamout BI (2015) Functional clinical outcomes in multiple sclerosis: current status and future prospects. Mult Scler Relat Disord 4(3):192–201. https://doi.org/10.1016/j.msard.2015.03.004 CrossRefPubMed

Confavreux C, Vukusic S (2014) The clinical course of multiple sclerosis. Handb Clin Neurol 122:343–369. https://doi.org/10.1016/B978-0-444-52001-2.00014-5 CrossRefPubMed

Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ, Wolinsky JS, Balcer LJ, Banwell B, Barkhof F, Bebo B Jr, Calabresi PA, Clanet M, Comi G, Fox RJ, Freedman MS, Goodman AD, Inglese M, Kappos L, Kieseier BC, Lincoln JA, Lubetzki C, Miller AE, Montalban X, O'Connor PW, Petkau J, Pozzilli C, Rudick RA, Sormani MP, Stuve O, Waubant E, Polman CH (2014) Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 83(3):278–286. https://doi.org/10.1212/WNL.0000000000000560 CrossRefPubMedPubMedCentral

Coret F, Perez-Miralles FC, Gascon F, Alcala C, Navarre A, Bernad A, Bosca I, Escutia M, Gil-Perotin S, Casanova B (2018) Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies. Mult Scler J Exp Transl Clin 4(2):2055217318783347. https://doi.org/10.1177/2055217318783347 CrossRefPubMedPubMedCentral

University of California SFMSET, Cree BA, Gourraud PA, Oksenberg JR, Bevan C, Crabtree-Hartman E, Gelfand JM, Goodin DS, Graves J, Green AJ, Mowry E, Okuda DT, Pelletier D, von Budingen HC, Zamvil SS, Agrawal A, Caillier S, Ciocca C, Gomez R, Kanner R, Lincoln R, Lizee A, Qualley P, Santaniello A, Suleiman L, Bucci M, Panara V, Papinutto N, Stern WA, Zhu AH, Cutter GR, Baranzini S, Henry RG, Hauser SL (2016) Long-term evolution of multiple sclerosis disability in the treatment era. Ann Neurol 80(4):499–510. https://doi.org/10.1002/ana.24747 CrossRef

Koch M, Kingwell E, Rieckmann P, Tremlett H, Neurologists UMC (2010) The natural history of secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 81(9):1039–1043. https://doi.org/10.1136/jnnp.2010.208173 CrossRefPubMed

Manouchehrinia A, Zhu F, Piani-Meier D, Lange M, Silva DG, Carruthers R, Glaser A, Kingwell E, Tremlett H, Hillert J (2018) Predicting risk of secondary progression in multiple sclerosis: a nomogram. Mult Scler. https://doi.org/10.1177/1352458518783667 CrossRefPubMed

10.

Voskuhl RR, Gold SM (2012) Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol 8(5):255–263. https://doi.org/10.1038/nrneurol.2012.43 CrossRefPubMedPubMedCentral

11.

Tremlett H, Yousefi M, Devonshire V, Rieckmann P, Zhao Y, Neurologists UBC (2009) Impact of multiple sclerosis relapses on progression diminishes with time. Neurology 73(20):1616–1623. https://doi.org/10.1212/WNL.0b013e3181c1e44f CrossRefPubMedPubMedCentral

12.

Scalfari A, Neuhaus A, Daumer M, Muraro PA, Ebers GC (2014) Onset of secondary progressive phase and long-term evolution of multiple sclerosis. J Neurol Neurosurg Psychiatry 85(1):67–75. https://doi.org/10.1136/jnnp-2012-304333 CrossRefPubMed

13.

Koch-Henriksen N, Sorensen PS (2010) The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 9(5):520–532. https://doi.org/10.1016/S1474-4422(10)70064-8 CrossRefPubMed

14.

Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302. https://doi.org/10.1002/ana.22366 CrossRefPubMedPubMedCentral

15.

Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol 58(6):840–846. https://doi.org/10.1002/ana.20703 CrossRefPubMed

16.

Saroufim P, Zweig SA, Conway DS, Briggs FBS (2018) Cardiovascular conditions in persons with multiple sclerosis, neuromyelitis optica and transverse myelitis. Mult Scler Relat Disord 25:21–25. https://doi.org/10.1016/j.msard.2018.07.011 CrossRefPubMed

17.

Briggs FBS, Yu JC, Davis MF, Jiangyang J, Fu S, Parrotta E, Gunzler DD, Ontaneda D (2019) Multiple sclerosis risk factors contribute to onset heterogeneity. Mult Scler Relat Disord 28:11–16. https://doi.org/10.1016/j.msard.2018.12.007 CrossRefPubMed

18.

Patsopoulos N, Baranzini SE, Santaniello A, Shoostari P, Cotsapas C, Wong G, James T, Replogle J, Vlachos IS (2019) Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. https://doi.org/10.1126/science.aav7188 CrossRef

19.

Fambiatos A, Jokubaitis V, Horakova D, Kubala Havrdova E, Trojano M, Prat A, Girard M, Duquette P, Lugaresi A, Izquierdo G, Grand'Maison F, Grammond P, Sola P, Ferraro D, Alroughani R, Terzi M, Hupperts R, Boz C, Lechner-Scott J, Pucci E, Bergamaschi R, Van Pesch V, Ozakbas S, Granella F, Turkoglu R, Iuliano G, Spitaleri D, McCombe P, Solaro C, Slee M, Ampapa R, Soysal A, Petersen T, Sanchez-Menoyo JL, Verheul F, Prevost J, Sidhom Y, Van Wijmeersch B, Vucic S, Cristiano E, Saladino ML, Deri N, Barnett M, Olascoaga J, Moore F, Skibina O, Gray O, Fragoso Y, Yamout B, Shaw C, Singhal B, Shuey N, Hodgkinson S, Altintas A, Al-Harbi T, Csepany T, Taylor B, Hughes J, Jun JK, van der Walt A, Spelman T, Butzkueven H, Kalincik T (2019) Risk of secondary progressive multiple sclerosis: a longitudinal study. Mult Scler. https://doi.org/10.1177/1352458519868990 CrossRefPubMed

20.

Cossburn M, Ingram G, Hirst C, Ben-Shlomo Y, Pickersgill TP, Robertson NP (2012) Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis. Mult Scler 18(1):45–54. https://doi.org/10.1177/1352458511417479 CrossRefPubMed

21.

Royston P (2006) Explained variation for survival models. Stata J 6(1):83–96. https://doi.org/10.1177/1536867x0600600105 CrossRef

22.

Zlotnik A, Abraira V (2015) A general-purpose nomogram generator for predictive logistic regression models. Stata J 15(2):537–546. https://doi.org/10.1177/1536867x1501500212 CrossRef

23.

Scalfari A, Lederer C, Daumer M, Nicholas R, Ebers GC, Muraro PA (2016) The relationship of age with the clinical phenotype in multiple sclerosis. Mult Scler 22(13):1750–1758. https://doi.org/10.1177/1352458516630396 CrossRefPubMed

24.

Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, Edan G (2010) Evidence for a two-stage disability progression in multiple sclerosis. Brain 133(Pt 7):1900–1913. https://doi.org/10.1093/brain/awq076 CrossRefPubMedPubMedCentral

25.

Mowry EM, Pesic M, Grimes B, Deen SR, Bacchetti P, Waubant E (2009) Clinical predictors of early second event in patients with clinically isolated syndrome. J Neurol 256(7):1061–1066. https://doi.org/10.1007/s00415-009-5063-0 CrossRefPubMedPubMedCentral

26.

D'Alessandro R, Vignatelli L, Lugaresi A, Baldin E, Granella F, Tola MR, Malagu S, Motti L, Neri W, Galeotti M, Santangelo M, Fiorani L, Montanari E, Scandellari C, Benedetti MD, Leone M (2013) Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study. J Neurol 260(6):1583–1593. https://doi.org/10.1007/s00415-013-6838-x CrossRefPubMed

27.

Spelman T, Meyniel C, Rojas JI, Lugaresi A, Izquierdo G, Grand'Maison F, Boz C, Alroughani R, Havrdova E, Horakova D, Iuliano G, Duquette P, Terzi M, Grammond P, Hupperts R, Lechner-Scott J, Oreja-Guevara C, Pucci E, Verheul F, Fiol M, Van Pesch V, Cristiano E, Petersen T, Moore F, Kalincik T, Jokubaitis V, Trojano M, Butzkueven H, Investigators MS (2016) Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice. Mult Scler. https://doi.org/10.1177/1352458516679893 CrossRefPubMed

28.

Marrie RA, Horwitz RI, Cutter G, Tyry T, Vollmer T (2011) Association between comorbidity and clinical characteristics of MS. Acta Neurol Scand 124(2):135–141. https://doi.org/10.1111/j.1600-0404.2010.01436.x CrossRefPubMed

29.

Koch M, Uyttenboogaart M, van Harten A, De Keyser J (2008) Factors associated with the risk of secondary progression in multiple sclerosis. Mult Scler 14(6):799–803. https://doi.org/10.1177/1352458508089361 CrossRefPubMed

30.

Vukusic S, Confavreux C (2003) Prognostic factors for progression of disability in the secondary progressive phase of multiple sclerosis. J Neurol Sci 206(2):135–137. https://doi.org/10.1016/s0022-510x(02)00426-4 CrossRefPubMed

31.

Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343(20):1430–1438. https://doi.org/10.1056/NEJM200011163432001 CrossRefPubMed

32.

Reilly GD, Mahkawnghta AS, Jelinek PL, De Livera AM, Weiland TJ, Brown CR, Taylor KL, Neate SL, Jelinek GA, Marck CH (2017) International differences in multiple sclerosis health outcomes and associated factors in a cross-sectional survey. Front Neurol 8:229. https://doi.org/10.3389/fneur.2017.00229 CrossRefPubMedPubMedCentral

33.

Briggs FB, Gunzler DD, Ontaneda D, Marrie RA (2017) Smokers with MS have greater decrements in quality of life and disability than non-smokers. Mult Scler 23(13):1772–1781. https://doi.org/10.1177/1352458516685169 CrossRefPubMedPubMedCentral

34.

Briggs FBS, Thompson NR, Conway DS (2019) Prognostic factors of disability in relapsing remitting multiple sclerosis. Mult Scler Relat Disord 30:9–16. https://doi.org/10.1016/j.msard.2019.01.045 CrossRefPubMed

35.

Hempel S, Graham GD, Fu N, Estrada E, Chen AY, Miake-Lye I, Miles JN, Shanman R, Shekelle PG, Beroes JM, Wallin MT (2017) A systematic review of modifiable risk factors in the progression of multiple sclerosis. Mult Scler 23(4):525–533. https://doi.org/10.1177/1352458517690270 CrossRefPubMed

36.

Handel AE, Williamson AJ, Disanto G, Dobson R, Giovannoni G, Ramagopalan SV (2011) Smoking and multiple sclerosis: an updated meta-analysis. PLoS ONE 6(1):e16149. https://doi.org/10.1371/journal.pone.0016149 CrossRefPubMedPubMedCentral

37.

Hedstrom AK, Hillert J, Olsson T, Alfredsson L (2013) Smoking and multiple sclerosis susceptibility. Eur J Epidemiol 28(11):867–874. https://doi.org/10.1007/s10654-013-9853-4 CrossRefPubMedPubMedCentral

38.

Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, Ebers GC (2010) The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain 133(Pt 7):1914–1929. https://doi.org/10.1093/brain/awq118 CrossRefPubMedPubMedCentral

39.

Scalfari A, Neuhaus A, Daumer M, Deluca GC, Muraro PA, Ebers GC (2013) Early relapses, onset of progression, and late outcome in multiple sclerosis. JAMA Neurol 70(2):214–222. https://doi.org/10.1001/jamaneurol.2013.599 CrossRefPubMed

40.

Marrie RA (2017) Comorbidity in multiple sclerosis: implications for patient care. Nat Rev Neurol 13(6):375–382. https://doi.org/10.1038/nrneurol.2017.33 CrossRefPubMed

41.

Marrie RA, Rudick R, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T (2010) Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 74(13):1041–1047. https://doi.org/10.1212/WNL.0b013e3181d6b125 CrossRefPubMedPubMedCentral

42.

Jakimovski D, Gandhi S, Paunkoski I, Bergsland N, Hagemeier J, Ramasamy DP, Hojnacki D, Kolb C, Benedict RHB, Weinstock-Guttman B, Zivadinov R (2019) Hypertension and heart disease are associated with development of brain atrophy in multiple sclerosis: a 5-year longitudinal study. Eur J Neurol 26(1):87–e88. https://doi.org/10.1111/ene.13769 CrossRefPubMed

43.

Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343(13):938–952. https://doi.org/10.1056/NEJM200009283431307 CrossRefPubMed

44.

Kister I, Munger KL, Herbert J, Ascherio A (2012) Increased risk of multiple sclerosis among women with migraine in the Nurses’ Health Study II. Mult Scler 18(1):90–97. https://doi.org/10.1177/1352458511416487 CrossRefPubMed

45.

Kister I, Caminero AB, Monteith TS, Soliman A, Bacon TE, Bacon JH, Kalina JT, Inglese M, Herbert J, Lipton RB (2010) Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course. J Headache Pain 11(5):417–425. https://doi.org/10.1007/s10194-010-0237-9 CrossRefPubMedPubMedCentral

46.

Pakpoor J, Handel AE, Giovannoni G, Dobson R, Ramagopalan SV (2012) Meta-analysis of the relationship between multiple sclerosis and migraine. PLoS ONE 7(9):e45295. https://doi.org/10.1371/journal.pone.0045295 CrossRefPubMedPubMedCentral

47.

Wijnands JM, Zhu F, Kingwell E, Zhao Y, Ekuma O, Lu X, Evans C, Fisk JD, Marrie RA, Tremlett H (2019) Five years before multiple sclerosis onset: phenotyping the prodrome. Mult Scler 25(8):1092–1101. https://doi.org/10.1177/1352458518783662 CrossRefPubMed

48.

Calabrese M, Gasperini C, Tortorella C, Schiavi G, Frisullo G, Ragonese P, Fantozzi R, Prosperini L, Annovazzi P, Cordioli C, Di Filippo M, Ferraro D, Gajofatto A, Malucchi S, Lo Fermo S, De Luca G, Stromillo ML, Cocco E, Gallo A, Paolicelli D, Lanzillo R, Tomassini V, Pesci I, Rodegher ME, Solaro C, Group R (2019) "Better explanations" in multiple sclerosis diagnostic workup: a 3-year longitudinal study. Neurology 92(22):e2527–e2537. https://doi.org/10.1212/WNL.0000000000007573 CrossRefPubMedPubMedCentral

49.

Solomon AJ, Bourdette DN, Cross AH, Applebee A, Skidd PM, Howard DB, Spain RI, Cameron MH, Kim E, Mass MK, Yadav V, Whitham RH, Longbrake EE, Naismith RT, Wu GF, Parks BJ, Wingerchuk DM, Rabin BL, Toledano M, Tobin WO, Kantarci OH, Carter JL, Keegan BM, Weinshenker BG (2016) The contemporary spectrum of multiple sclerosis misdiagnosis: a multicenter study. Neurology 87(13):1393–1399. https://doi.org/10.1212/WNL.0000000000003152 CrossRefPubMedPubMedCentral

50.

Kaisey M, Solomon AJ, Luu M, Giesser BS, Sicotte NL (2019) Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers. Mult Scler Relat Disord 30:51–56. https://doi.org/10.1016/j.msard.2019.01.048 CrossRefPubMed

51.

Cools N, Ponsaerts P, Van Tendeloo VF, Berneman ZN (2007) Regulatory T cells and human disease. Clin Dev Immunol 2007:89195. https://doi.org/10.1155/2007/89195 CrossRefPubMed

52.

Marrie RA, Reider N, Cohen J, Stuve O, Trojano M, Sorensen PS, Reingold SC, Cutter G (2015) A systematic review of the incidence and prevalence of cancer in multiple sclerosis. Mult Scler 21(3):294–304. https://doi.org/10.1177/1352458514564489 CrossRefPubMedPubMedCentral

53.

International Multiple Sclerosis Genetics C (2011) Genome-wide association study of severity in multiple sclerosis. Genes Immun 12(8):615–625. https://doi.org/10.1038/gene.2011.34 CrossRef

54.

Baranzini SE, Wang J, Gibson RA, Galwey N, Naegelin Y, Barkhof F, Radue EW, Lindberg RL, Uitdehaag BM, Johnson MR, Angelakopoulou A, Hall L, Richardson JC, Prinjha RK, Gass A, Geurts JJ, Kragt J, Sombekke M, Vrenken H, Qualley P, Lincoln RR, Gomez R, Caillier SJ, George MF, Mousavi H, Guerrero R, Okuda DT, Cree BA, Green AJ, Waubant E, Goodin DS, Pelletier D, Matthews PM, Hauser SL, Kappos L, Polman CH, Oksenberg JR (2009) Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis. Hum Mol Genet 18(4):767–778. https://doi.org/10.1093/hmg/ddn388 CrossRefPubMed

55.

George MF, Briggs FB, Shao X, Gianfrancesco MA, Kockum I, Harbo HF, Celius EG, Bos SD, Hedstrom A, Shen L, Bernstein A, Alfredsson L, Hillert J, Olsson T, Patsopoulos NA, De Jager PL, Oturai AB, Sondergaard HB, Sellebjerg F, Sorensen PS, Gomez R, Caillier SJ, Cree BA, Oksenberg JR, Hauser SL, D'Alfonso S, Leone MA, Martinelli Boneschi F, Sorosina M, van der Mei I, Taylor BV, Zhou Y, Schaefer C, Barcellos LF (2016) Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies. Neurol Genet 2(4):e87. https://doi.org/10.1212/NXG.0000000000000087 CrossRefPubMedPubMedCentral

56.

Crielaard L, Kavaliunas A, Ramanujam R, Olsson T, Hillert J, Stridh P, Kockum I, Manouchehrinia A (2019) Factors associated with and long-term outcome of benign multiple sclerosis: a nationwide cohort study. J Neurol Neurosurg Psychiatry 90(7):761–767. https://doi.org/10.1136/jnnp-2018-319913 CrossRefPubMed

57.

Healy BC, Liguori M, Tran D, Chitnis T, Glanz B, Wolfish C, Gauthier S, Buckle G, Houtchens M, Stazzone L, Khoury S, Hartzmann R, Fernandez-Vina M, Hafler DA, Weiner HL, Guttmann CR, De Jager PL (2010) HLA B*44: protective effects in MS susceptibility and MRI outcome measures. Neurology 75(7):634–640. https://doi.org/10.1212/WNL.0b013e3181ed9c9c CrossRefPubMedPubMedCentral

58.

Lysandropoulos AP, Perrotta G, Billiet T, Ribbens A, Du Pasquier R, Pot Kreis C, Maggi P, Theaudin M (2020) Human leukocyte antigen genotype as a marker of multiple sclerosis prognosis. Can J Neurol Sci 47(2):189–196. https://doi.org/10.1017/cjn.2019.329 CrossRefPubMed

59.

Horton M, Rudick RA, Hara-Cleaver C, Marrie RA (2010) Validation of a self-report comorbidity questionnaire for multiple sclerosis. Neuroepidemiology 35(2):83–90. https://doi.org/10.1159/000311013 CrossRefPubMed

Title: Predicting onset of secondary-progressive multiple sclerosis using genetic and non-genetic factors
Authors: Elina Misicka
Corriene Sept
Farren B. S. Briggs
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keyword: Multiple Sclerosis
Published in: Journal of Neurology / Issue 8/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-09850-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Predicting onset of secondary-progressive multiple sclerosis using genetic and non-genetic factors

Abstract

Background

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objective

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 8/2020

Correction to: Caregiver burden and its related factors in advanced Parkinson’s disease: data from the PREDICT study

Cognitive impairment in early MS: contribution of white matter lesions, deep grey matter atrophy, and cortical atrophy

Bilateral posterior semicircular canal dysfunction: a new finding with video head impulse test

Spatial and egocentric mental rotation in patients with cervical dystonia

Disease activity outcomes with different washout periods after switching from natalizumab to an alternative disease-modifying therapy

Parkinsonism as a late presentation of lymphomatosis cerebri following high-dose chemotherapy with autologous stem cell transplantation for primary central nervous system lymphoma