Hopp til innhold
NHI.no
Annonse
Informasjon

Årsaker til MS (multippel sklerose)

På tross av mye forskning over mange år er den egentlige årsaken til MS enda ukjent.

Myelin
Ved autoimmune sykdommer vil immunforsvaret angripe ulike vev i kroppen. Ved MS er det myelinet rundt nervecellene som angripes.

Sist oppdatert:

7. nov. 2018

Den vanligste teorien for utvikling av multippel sklerose (MS) er at en kombinasjon av arveanlegg (genetisk disposisjon) og en faktor i miljøet (virus, tobakk, vitamin D-mangel) lurer kroppens immunforsvar til å angripe myelinet i hjernecellene. Myelin er den skjeden som omhyller og beskytter nervetrådene, tilsvarende den hvite isolasjonen rundt en elektrisk ledning (se ingressbilde, der vises skadet myelin øverst og frisk under). En slik sykdom, der immunforsvaret angriper kroppens eget vev, kalles en autoimmun sykdom.

Annonse

Immunforsvarets rolle ved MS

Immunforsvarets funksjon er å holde kroppen fri for bakterier, virus og andre skadelige stoffer, samt å reparere skader. Når en infeksjon eller skade oppstår, sendes store mengder hvite blodceller til stedet for å forsøke å holde kroppen frisk. De hvite blodcellene dreper og spiser bakterier og virus, og produserer antistoffer som skader de fremmede inntrengerne. I tillegg produseres små stoffer kalt cytokiner, som forsterker betennelsen og tiltrekker enda flere hvite blodceller.

Området der de hvite blodcellene samler seg, blir rødt, hovent, ømt og varmt. I dagligtale sier vi at det er oppstått en betennelse, og det medisinske ordet for dette er inflammasjon.

Normalt vil en slik inflammasjon begrense seg selv og gå tilbake når skaden er reparert, eller inntrengerne er fjernet. Ved autoimmune sykdommer vil immunforsvaret imidlertid fortsette å være aktivt og angripe ulike vev i kroppen. Man tror at dette skyldes en misforståelse i immunforsvaret, der immunforsvaret opplever at kroppens egne celler er fremmede inntrengere som må fjernes. Ved MS er det myelinet rundt nervecellene som angripes. Andre eksempler på autoimmune sykdommer er leddgikt og diabetes type 1.

Hvorfor angriper immunforsvaret myelin ved MS?

Forskerne antar at autoimmune sykdommer oppstår fordi immunforsvaret tror at kroppens egne celler er fremmede inntrengere som må fjernes. Denne misforståelsen kan oppstå etter en infeksjon med virus eller bakterier som kjemisk sett ligner på kroppens eget vev. Når den fremmede intrengeren er fjernet, går immunforsvaret løs på kroppen selv i stedet.

Mange eksperter tror at en virusinfeksjon kan starte denne reaksjonen ved MS, men ingen vet sikkert hvilket virus det dreier seg om. Størst mistanke har man til Epstein-Barr viruset (årsaken til kyssesyke), men også andre virus har vært i søkelyset. Dette er vanlige virus, som mange av oss har vært smittet av uten å få MS. Forskerne tror imidlertid at de som får MS, har bestemte gener som gjør dem spesielt utsatte for å utvikle sykdommen. Det dreier seg sannsynligvis om en kombinasjon av flere gener, og man tror at genene HLA-DR15 og HLA-DQ6 er sentrale.

Teorien om at en kombinasjon av genetikk og virusinfeksjon er årsaken til MS, kan også forklare hvorfor sykdommen er vanligere i bestemte områder av verden og i enkelte folkegrupper. I områder med mye MS, f.eks Skandinavia, Skottland og USA, er det trolig en høy forekomst av de aktuelle virusartene, og mange personer med genetisk disposisjon. Man kan også tenke seg at de folkegruppene som har lite MS, selv om de lever i områder med høy forekomst av sykdommen, f.eks samene, har gener som virker beskyttende.

Annonse

Sammenhengen mellom genetikk og MS bekreftes også av at det er en viss arvelighet for sykdommen. Barn av foreldre med MS har høyere risiko for å utvikle sykdommen enn andre barn. Men MS er sjelden, og selv om risikoen for å få et barn med MS er økt, er risikoen likevel fortsatt liten.

Røyking

Det er holdepunkter for at røyking også kan øke risikoen for å utvikle MS. Det er ikke kjent hvordan dette skjer, men det kan tenkes at tobakksbruk kan påvirke immunapparatet og muligens bidra til å forsterke eller utløse den autoimmune prosessen som er beskrevet over.

Vitamin D

Vitamin D produseres i store mengder i huden ved soleksponering. Det er sett at MS er hyppigere i områder på kloden med liten solbelastning og lave vitamin D-nivåer i kroppen. Det er også funnet indikasjoner på at høye nivåer av vitamin D kan ha en beskyttende effekt på utviklingen av MS. De endelige sammenhengene er ikke klarlagt, men det er sannsynlig at det med tiden vil komme til mer kunnskap på dette feltet. Det diskuteres hvorvidt økt tilførsel av vitamin D gjennom sollys, kosthold eller kosttilskudd, kan minske antallet nye tilfeller med MS. En stor studie (Meta-analyse fra Cochrane fra 2018 ) konkluderer med manglende dokumentasjon for assosiasjon mellom MS og vitamin D, og at behandling med vitamin D ikke har noen effekt - men sier samtidig at siste ord enda ikke er sagt rundt dette.

Dette dokumentet er basert på det profesjonelle dokumentet Multippel sklerose . Referanselisten for dette dokumentet vises nedenfor

  1. Luzzio C. Multiple sclerosis. Medscape, last updated Jan 27, 2016. emedicine.medscape.com
  2. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17: 162-73. pmid:29275977 PubMed
  3. Midgard R, Beiske AG, Celius EG, Jensen D, Hovdal H, Mellgren SI, Myhr K-M. Nye diagnostiske kriterier ved multippel sklerose. Tidsskr Nor Lægeforen 2003; 123: 1345-8. Tidsskrift for Den norske legeforening
  4. Compston A. Genetic epidemiology of multiple sclerosis. J Neurol Neurosurg Psychiatry 1997; 62: 553-61. PubMed
  5. Midgard R. Incidence and prevalence of multiple sclerosis in Norway. Acta Neurol Scand 2012; 126 (Suppl 195): 36-42. PMID: 23278655 PubMed
  6. Berg-Hansen P, Moen SM, Harbo HF, Celius EG. High prevalence and no latitude gradient of multiple sclerosis in Norway. Mult Scler 2014; 20: 1780-2. PMID: 24603884 PubMed
  7. Grytten N, Torkildsen Ø, Myhr KM. Time trends in the incidence and prevalence of multiple sclerosis in Norway during eight decades. Acta Neurol Scand Suppl. 2015; 132: 29-36. PMID: 26046556 PubMed
  8. Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician 2004; 70: 1935-44. PubMed
  9. Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 2022; 375: 296-301. pmid:35025605 PubMed
  10. Belbasis L, Bellou V, Evangelou E, et al. Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. Lancet Neurol. 2015; 14: 263-73. doi: 10.1016/S1474-4422(14)70267-4 DOI
  11. DeLorenze GN, Munger KL, Lennette ET, Orentreich N, Vogelman JH, Ascherio A. Epstein-Barr Virus and Multiple Sclerosis. Evidence of Association From a Prospective Study With Long-term Follow-up. Arch Neurol 2006; 63: (doi:10.1001/archneur.63.6.noc50328). DOI
  12. Aschiero A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol 2007; 61: 504-13. PubMed
  13. Ebers GC. Environmenrtal factors and multiple sclerosis. Lancet Neurology 2008; 7: 268-77. PubMed
  14. Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol 2007; 61: 288-99. PubMed
  15. Ramogapalan SV, Maugeri NJ, Handunnetthi L, et al. Expression of the Multiple Sclerosis-associated MHC class II allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet 2009; 5: e1000369. PubMed
  16. The International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium. Genetic risk and primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011: 476: 214-219.
  17. Xu Y, Hiyoshi A, Smith KA, et al. Association of Infectious Mononucleosis in Childhood and Adolescence With Risk for a Subsequent Multiple Sclerosis Diagnosis Among Siblings. JAMA Netw Open 2021. doi:10.1001/jamanetworkopen.2021.24932 DOI
  18. Staples J, Ponsonby A-L, Lim L. Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis. BMJ 2010; 340: c1640. BMJ (DOI)
  19. Ascherio A, Munger KL, White R, et al. Vitamin D as an early predictor of Multiple sclerosis activity and progression. JAMA Neurol 2014. doi:10.1001/jamaneurol.2013.5993 DOI
  20. Munger KL, Hongell K, Åivo J, et al. 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology 2017; 89: 1-6. pmid:28904091 PubMed
  21. Jagannath VA, Filippini G, Di Pietrantonj C, et al. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. 2018 Sep 24;9:CD008422. doi: 10.1002/14651858.CD008422.pub3. (Review) PMID: 30246874 PubMed
  22. Lucchinetti CF, Bruck W, Rodriguez M, Lassmann H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity in pathogenesis. Brain Pathol 1996; 6: 259-74. PubMed
  23. Mohr DC, Hart SL, Julian L, Cox D, Pelletier D. Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. BMJ 2004; 328: 731. PubMed
  24. Frohman EM, Racke MK, Raine CS. Multiple sclerosis - the plaque and its pathogenesis. N Engl J Med 2006; 354: 942-55. PubMed
  25. Bø L, Vedeler CA, Nyland HI et al. Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler 2003;9: 323-31. PubMed
  26. Bø L, Vedeler CA, Nyland HI et al. Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 2003; 62: 723-32. PubMed
  27. Geurts JJ, Bo L, Pouwels PJ, Castelijns JA, Polman CH, Barkhof F. Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. AJNR Am J Neuroradiol 2005; 26: 572-7. PubMed
  28. Barnett MH, Henderson AP, Prineas JW. The macrophage in MS: just a scavenger after all? Pathology and pathogenesis of the acute MS Lesion. Mult Scler 2006; 12: 121-32. PubMed
  29. Trapp BD, Vignos M, Dudman J, et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. Lancet Neurol 2018; 17: 870-84. pmid:30143361 PubMed
  30. Jersild C, Svejgaard A, Fog T. HL-A antigens and multiple sclerosis. Lancet 1972; 1: 1240-1. PubMed
  31. Nasjonale faglige retningslinjer for diagnostikk, attakk- og sykdomsmodifiserende behandling av multippel sklerose. Helsedirektoratet IS-1905. ISBN – 978-82-8081-226-1. November 2011.
  32. Grytten N, Torkildsen Ø, Aarseth JH, Benjaminsen E, Celius EG, Dahl OP, Holmøy T, Løken-Amsrud K, Midgard R, Myhr KM, Risberg G, Vatne A, Kampman MT. Month of birth as a latitude-dependent risk factor for multiple sclerosis in Norway. Mult Scler 2012; 19: 1028-34 PubMed
  33. Torkildsen Ø, Aarseth JH, Benjaminsen E, Celius EG, Holmøy T, Kampman MT, Løken-Amsrud K, Midgard R, Myhr KM, Riise T, Grytten N. Month of birth and risk of multiple sclerosis: confounding and adjustments. Annals of Clinical and Translational Neurology 2014; 1 (2): 141-44
  34. Rodríguez Cruz PM, Matthews L, Boggild M, et al. Time- and Region-Specific Season of Birth Effects in Multiple Sclerosis in the United Kingdom. JAMA Neurol 2016. pmid:27366989 PubMed
  35. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniare P, Moreau T, and the Pregnancy in MS Group. Rate of pregnancy-related relapse in multiple sclerosis. N Engl J Med 1998; 339: 285-91. New England Journal of Medicine
  36. Nasjonal faglig retningslinje. Multippel sklerose. Først publisert 30. mai 2017. Sist faglig oppdatert 24. november 2021. www.helsedirektoratet.no
  37. Forslin Y, Granberg T, Jumah AA, et al. Incidence of Radiologically Isolated Syndrome: A Population-Based Study. AJNR Am J Neuroradiol 2016; 37: 1017-22. pmid:26846927 PubMed
  38. Granberg T, Martola J, Aspelin P, et al. Radiologically isolated syndrome: an uncommon finding at a university clinic in a high-prevalence region for multiple sclerosis. BMJ Open 2013. pmid:24189079 PubMed
  39. Lebrun C, Bensa C, Debouverie M, et al. Association between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: follow-up of 70 patients. Arch Neurol 2009; 66: 841-6. pmid:19597085 PubMed
  40. Moore F, Okuda DT. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 2009; 73: 1714. pmid: 19918002 PubMed
  41. Dahl OP, Stordal E, Lydersen S, Midgard R. Anxiety and depression in multiple sclerosis. A comparative population-based study in Nord-Trøndelag, Norway. Mult Scler 2009; 15: 1495-501. PubMed
  42. Gustavsen S, Olsson A, Søndergaard HB, et al. The association of selected multiple sclerosis symptoms with disability and quality of life: a large Danish self-report survey. BMC Neurol. 2021 Aug 16;21(1):317. PMID: 34399707. PubMed
  43. Broch L, Simonsen CS, Flemmen HØ, et al. High prevalence of fatigue in contemporary patients with multiple sclerosis. Mult Scler J Exp Transl Clin. 2021 Mar 18;7(1):2055217321999826. PMID: 33796331. PubMed
  44. Hoff JM, Dhayalan M, Midelfart A, et al. Synsproblemer ved multippel sklerose. Tidsskr Nor Legeforen 2019. doi:10.4045/tidsskr.18.0786 DOI
  45. Filippi M, Rocca MA, Ciccarelli O, et al . MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol 2016; 15: 292-303. pmid:26822746 PubMed
  46. Tintoré M, Rovira A, Martinez MJ, Rio J, Diaz-Villoslada P, Brieva L et al. Isolated demyelinating syndromes: comparison of different MRI imaging criteria to predict conversion to clinically definite multiple sclerosis. Am J Neuroradiol 2000; 21: 702 - 6. PubMed
  47. Bakke SJ, Lilleås, F, Smievoll AI, Myhr G, Nakstad PJ, Bajic R et al. Bruk av MR i diagnostikk av multippel sklerose Tidsskr Nor Lægeforen 2003; 123: 1349 - 51. PubMed
  48. Whiting P, Harbord R, Main C, et al. Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis: systematic review. BMJ 2006; 15: 875-84. British Medical Journal
  49. Andersson M, Alvarez-Cermeño J, Bernardi G, Cogato I, Fredman P, Frederiksen J et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 1994; 57: 897 - 902. PubMed
  50. Berger T, Rubner P, Schautzer F, et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003; 349: 139-45. PubMed
  51. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004; 364: 2106-12. PubMed
  52. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. JEM 2005; 202: 473-7. PubMed
  53. Varhaug KN, Barro C, Bjørnevik K, et al. Neurofilament light chain predicts disease activity in relapsing-remitting MS. Send to Neurol Neuroimmunol Neuroinflamm. 2017; 5: 422. pmid:29209636 PubMed
  54. Tjelle TE, Rose C, Ohm IK, Pike E, Håheim, LL, Bidonde J, Fretheim A, Ju-vet LK, Disease-modifying treatments for relapsing remitting multiple sclerosis, including rituximab. A health technology assessment. Report from Norwegian Institute of Public Health, Folkehelseinstituttet, Oslo, June 2019 www.fhi.no
  55. Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Eur J Neurol 2018. pmid:29352526 PubMed
  56. Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology 2018; 90: 777-88. pmid:29686116 PubMed
  57. Polman CH, Uitdehaag BMJ. Drug treatment of multiple sclerosis. BMJ 2000; 321: 490-4. PubMed
  58. Giovannoni G, Comi G, Cook S, et al. A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis. N Engl J Med 2010; 362: 416-26. pmid:20089960 PubMed
  59. Leist TP, Comi G, Cree BAC, et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol 2014; 13: 257-67. pmid:24502830 PubMed
  60. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med 2017; 376: 221-34. pmid:28002679 PubMed
  61. Granqvist M, Boremalm M, Poorghobad A, et al. Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis. JAMA Neurol 2018; 75: 320-7. pmid:29309484 PubMed
  62. Pearson M, Dieberg G, Smart N. Exercise as a Therapy for Improvement of Walking Ability in Adults With Multiple Sclerosis: A Meta-Analysis. Arch Phys Med Rehabil. 2015; 96: 1339-48. doi:10.1016/j.apmr.2015.02.011 DOI
  63. European study group on interferon b -1b in secondary progressive MS. Placebo-controlled multicentre randomised trial of interferon b -1b in treatment of secondary progressive multiple sclerosis. Lancet 1998; 352: 1491-7. PubMed
  64. Aarli JA. Betainterferon ved multippel sklerose - hvem skal behandles? Tidsskr Nor Lægeforen 1999; 119: 3114. PubMed
  65. Jacobs LD, Beck RW, Simon JH, Kinkel RP, et al. Intramuscular interferon beta-1-a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000 28; 343: 898-904. PubMed
  66. Comi G, Filippi M, Barkhof F et al. Effect of early interferon treatment on conversion to definite multiple sclerosis. Lancet 2001; 357: 1576-82. PubMed
  67. Filippi M, Rovaris M, Inglese M, Barkhof F et al. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet 2004; 364: 1489-96. PubMed
  68. Soelberg Sorensen P, Ross C, Clemmesen KM, Bendtzen K, Frederiksen JL, Jensen K, Kristensen O, Petersen T, Rasmussen S, Ravnborg M, Stenager E, Koch-Henriksen N and the Danish MS Study Group. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 2003; 362: 1184-91. PubMed
  69. Sørensen PS, Deisenhammer F, Duda P, Hohlfeld R, Myhr KM, Palace J et al. Guidelines on use of anti-IFN-beta antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN-? antibodies in multiple sclerosis. Eur J Neurol 2005; 12: 817-27. PubMed
  70. Comi G, Martinelli M, Rodegher M, et al. Eff ect of glatiramer acetate on conversion to clinically defi nite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 2009; 374: 1503-11. PubMed
  71. Papadopoulou A, Kappos L, Sprenger T. Teriflunomide for oral therapy in multiple sclerosis. Expert Rev Clin Pharmacol. 2012; 5): 617-28. PubMed PMID: 23234322 PubMed
  72. O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS; TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365:1293-303. doi: 10.1056/NEJMoa1014656.
  73. Vermersch P, Czlonkowska A, Grimaldi LM, et al; for the TENERE Trial Group. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler. 2013 Nov 21. Epub ahead of print PubMed PMID: 24126064 PubMed
  74. Miller et al. TOPIC main outcomes: efficacy and safety of once-daily oral teriflunomide in patients with clinically isolated syndrome. ECTRIMS Copenhagen 2013.
  75. He D, Zhang C, Zhao X, et al. Teriflunomide for multiple sclerosis. Cochran Database Syst Rev 2016; 3: CD009882. pmid: 27003123 PubMed
  76. Sartori A, Carle D, Freedman MS. Teriflunomide: a novel oral treatment for relapsing multiple sclerosis. Expert Opin Pharmacother. 2014;15(7):1019-27. PMID: 24742277. PubMed
  77. Linker RA, Gold R. Dimethyl fumarate for treatment of multiple sclerosis: mechanism of action, effectiveness, and side effects. Curr Neurol Neurosci Rep. 2013 Nov;13(11):394 PubMed
  78. Xu Z, Zhang F, Sun F, Gu K, Dong S, He D. Dimethyl fumarate for multiple sclerosis. Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No.: CD011076. DOI: 10.1002/14651858.CD011076.pub2. DOI
  79. Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899-910. New England Journal of Medicine
  80. Miller DH, Soon D, Fernando KT, et al. For the AFFIRM investigators. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology 2007; 68: 1390-1401. Neurology
  81. Havrdova E, Galetta S, Hutchinson M, et al. Effect og natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab safety and efficacy in relapsing-remitting multiple sclerosis (AFFIRM) study. Lancet 2009; 8: 254-60. PubMed
  82. Zhovtis Ryerson L, Frohman TC, Foley J, et al. Extended interval dosing of natalizumab in multiple sclerosis. J Neurol Neurosurg Psychiatry 2016. pmid: 26917698 PubMed
  83. Bomprezzi R, Pawate S. Extended interval dosing of natalizumab – a two-center, 7-year experience. Ther Adv Neurol Disord. ; 7: 227-31. pmid:25342976 PubMed
  84. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366: 1870-80. New England Journal of Medicine
  85. Sosial- og helsedirektoratet: Behandling av multippel sklerose (MS) med natalizumab Oppstart, gjennomføring og avslutning av behandling. 6/2007.
  86. Kappos L, Bates D, Hartung H-P et al. Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol 2007; 6: 431-41. PubMed
  87. Kappos L, Radue E-W, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362: .
  88. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimode or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362: .
  89. Brown JW, Coles AJ. Alemtuzumab: evidence for its potential in relapsing-remitting multiple sclerosis. Drug Des Devel Ther. 2013;7:131-8. doi: 10.2147/DDDT.S32687 DOI
  90. Cohen JA, Coles AJ, Arnold DL, et al; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012; 380:1819-28. doi: 10.1016/S0140-6736(12)61769-3. DOI
  91. Coles AJ, Twyman CL, Arnold DL, et al; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. DOI
  92. Haghikia A, Dendrou CA, Schneider R, et al. Severe B-cell-mediated CNS disease secondary to alemtuzumab therapy. Lancet Neurology 2017; 16: 104-6. doi:10.1016/S1474-4422(16)30382-9 DOI
  93. Demko S, Summers J, Keegan P, Pazdur R. FDA drug approval summary: alemtuzumab as single-agent treatment for B-cell chronic lymphocytic leukemia. Oncologist. 2008 Feb;13(2):167-74. PMID: 18305062 PubMed
  94. Hawker J, O’Connor P, Freedman MS et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 2009; 66: 460-71 PubMed
  95. Alping P, Frisell T, Novakova L, et al. Rituximab versus fingolimod after natalizumab in multiple sclerosis patients. Ann Neurol 2016; 79: 950-8. pmid: 27038238 PubMed
  96. Nye Metoder: Siponimod (Mayzent). Beslutning 21.06.21. Nettsiden besøkt 05.10.11. nyemetoder.no
  97. Nevro-NEL: Behandling av MS. Nettside besøkt 05.10.21. nevrologi.legehandboka.no
  98. Burt RK, Balabanov R, Han X, et al. Association of Nonmyeloablative Hematopoietic Stem Cell Transplantation With Neurological Disability in Patients With Relapsing-Remitting Multiple Sclerosis. JAMA 2015; 313(3): 275-84. doi:10.1001/jama.2014.17986 DOI
  99. Muraro PA, Pasquini M, Atkins HL et al. Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurol. Published online February 20, 2017. doi:10.1001/jamaneurol.2016.5867 DOI
  100. Burman J et al. Autologous hematopoietic stem cell transplantation for aggressive multiple sclerosis. The Swedish experience. J Neurol Neurosurg Psychiatry 2014; Feb 19 – Epub ahead of print
  101. Atkins HL, Bowman M, Allan D, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet 2016. pmid:27291994 PubMed
  102. Burton JM, O'Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database of Syst Rev 2012, Issue 12. Art. No.: CD006921. DOI: 10.1002/14651858.CD006921.pub3. DOI
  103. Morrow SA, Stoian CA, Dmitrovic J, Chan SC, Metz LM. The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis. Neurology 2004; 63: 1079-80. Neurology
  104. Sellebjerg F, Barnes D, Fillippini G, Midgard R, Montalban X, Rieckmann P et al. EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses. Eur J Neurol 2005; 12: 939-46. PubMed
  105. Montalban X, Hauser SL, Kappos L et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med 2017; 376: 209-20. pmid:28002688 PubMed
  106. Chataway J, Schuerer N, Alsanousi A, et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014 Mar 18.
  107. Shakespeare D, Boggild M, Young CA. Anti-spasticity agents for multiple sclerosis. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD001332. DOI: 10.1002/14651858.CD001332. DOI
  108. Smedal T, Gjelsvik B, Lygren H, Borgmann R, Waje-Andreassen U, Grønning M. Botulinumtoksin A - effekt på spastisitet. Tidsskr Nor Lægeforen 2001; 121: 3277-80. PubMed
  109. Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry 2005; 76: 1664-9. PubMed
  110. Novotna A et al. A randomised, double-blind, placebo-controlled, parallell-group, enriched study of nabiximols (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 2011; 18: 1122-31. PubMed
  111. Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomised, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 2005; 65: 812-9. Neurology
  112. Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ, doi:10.1136/bmj.38149.566979.AE (published 16 July 2004).
  113. Freeman RM, Adekanmi O, Waterfield MR, Waterfield AE, Wright D, Zajicek J. The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicenter, randomised placebo-controlled trial (CAMS-LUTS). Int Urogynecol J Pelvic Floor Dysfunct 2006; Mar 22 Epub ahead of print
  114. Yadav V, Bever C, Bowen J, et al. Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis. Neurology 2014; 82: 1083-92. Neurology
  115. Stankoff B, Waubant E, Confavreux C, Edan G, Debouverie M, Rumbach L et al. Modafinil for fatigue in MS. Neurology 2005; 64: 1139-43. Neurology
  116. Goodman AD, Brown TR, Krupp LB, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet 2009; 373: 732-38. PubMed
  117. Simpson R, Simpson S, Ramparsad N, et al. Mindfulness-based interventions for mental well-being among people with multiple sclerosis: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2019. PMID: 31196913 PubMed
  118. McLoughlin JV, Lord SR, Barr CJ, et al. Dorsiflexion assist orthosis reduces the physiological cost and mitigates deterioration in strength and balance associated with walking in people with multiple sclerosis.. Arch Phys Med Rehabil 2015; 96: 226-32. doi:10.1016/j.apmr.2014.09.005 DOI
  119. Thomas S, Thomas PW, Kersten P, et al. A pragmatic parallel arm multi-centre randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based fatigue management programme (FACETS) for people with multiple sclerosis. J Neurol Neurosurg Psychiatry 2013. pmid:23695501 PubMed
  120. Heine M, van de Port I, Rietberg MB, et al. Exercise therapy for fatigue in multiple sclerosis. Cochrane Database Syst Rev 2015; 9: CD009956. doi:10.1002/14651858.CD009956.pub2 DOI
  121. Dalgas U, Stenager E. Multipel sklerose og fysisk træning. Ugeskr Læger 2005; 167: 1495-9. PubMed
  122. Petajan JH, White AT. Recommendations for physical activity in patients with multiple sclerosis. Sports Med 1999; 27: 179-91. PubMed
  123. Sutherland G, Andersen MB. Exercise and multiple sclerosis: physiological, psychological, and quality of life issues. J Sports Med Phys Fitness 2001; 41: 421-32. PubMed
  124. Krysko KM, Rutatangwa A, Graves J et al. Association Between Breastfeeding and Postpartum Multiple Sclerosis Relapses A Systematic Review and Meta-analysis. JAMA Neurol 2019. epub 4173. pmid:31816024 PubMed
  125. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014 Jul 15;83(3):278-86. Epub 2014 May 28. PMID: 24871874; PMCID.
  126. Weinshenker BG, Bass B, Rice GPA, et al. The natural history of multiple sclerosis: a geographically based study. 1. Clinical course and disability. Brain 1980; 112: 133-46. PubMed
  127. Nicholas R, Rashid W. Multiple sclerosis. Am Fam Physician. 2013 May 15;87(10):712-4. PMID: 23939450 PubMed
  128. Marrie RA, Elliott L, Marriott J, et al. Effect of comorbidity on mortality in multiple sclerosis. Neurology 2015. pmid:26019190 PubMed
  129. Bø L. MS-behandlingen – og behovet for bedre beslutningsprosesser. Dagens Medisin 24.02.2020. www.dagensmedisin.no
  130. RELIS. Lavdose naltrekson (LDN): Mindre smertestillende, men uendret MS-medisinering. 08.11.2017, siden besøkt 22.03.18. relis.no
  131. Myhr K-M, Harbo HF. Multippel sklerose - en sykdom med kompleks genetikk. Tidsskr Nor Lægeforen 2003; 123: 2723-6. PubMed
  132. Levin LI, Munger KL, Rubertone MV, et al. Multiple sclerosis and Epstein-Barr virus. JAMA 2003; 289: 1533-6. PubMed
  133. Achiron A, Kishner I, Sarova-Pinhas I, et al. Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Arch Neurol 2004; 61: 1515-20. PubMed
  134. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292-302. PubMed
  135. Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G. Mitoxantrone for multiple sclerosis. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD002127. DOI: 10.1002/14651858.CD002127.pub3. DOI
Annonse
Annonse