Journal of Neurology

, Volume 255, Supplement 6, pp 109–114 | Cite as

Cerebral MRI lesions and anti-tumor necrosis factor-alpha therapy

  • Alexander Winkelmann
  • Robert Patejdl
  • Sabine Wagner
  • Reiner Benecke
  • Uwe Klaus Zettl


We discuss two cases receiving different anti-tumornecrosis-factor alpha antagonists (anti-TNF-α); one for psoriatic arthritis (PA) and the other for ankylosing spondylitis (AS). Due to neurological symptoms cerebral magnetic resonance imaging (MRI) was performed and cerebral lesions were detected. Our interpretations of these cerebral lesions and the resulting diagnostic and therapeutic consequences are presented in regard of data published in the medical literature.

Key words

multiple sclerosis demyelination anti-TNF-alpha-therapy cerebral lesions 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Barkhof F, Filippi M, Miller DH, ScheltensP, Campi A, Polman CH, Comi G,Adèr HJ, Losseff N, Valk J (1997) Comparisonof MRI criteria at first presentationto predict conversion to clinicallydefinite multiple sclerosis. Brain120:2059–2069PubMedCrossRefGoogle Scholar
  2. 2.
    Bellesi M, Logullo F, DiBella P, ProvincialiL (2006) CNS demyelination duringanti-tumor necrosis factor alphatherapy. J Neurol 253:668–669PubMedCrossRefGoogle Scholar
  3. 3.
    Bensouda-Grimaldi L, Mullemann D,Valat JP, Autret-leca E (2007) Adalimumab-associated Multiple Sclerosis.J Rheumatol 34:239–240PubMedGoogle Scholar
  4. 4.
    Calin A (1989) Is there an associationbetween ankylosing spondylitis andmultiple sclerosis? Ann Rheum Dis48:971–972PubMedCrossRefGoogle Scholar
  5. 5.
    Cellerini M, Gabbrielli S, Bongi SM(2001) Cerebral magnetic resonanceimaging in a patient with ankylosingspondylitis and multiple sclerosis-likesyndrome. Neuroradiology 43:1067–1069PubMedCrossRefGoogle Scholar
  6. 6.
    Enayati PJ, Papadakis KA (2005) Associationof anti-tumor necrosis factortherapy with the development ofmultiple sclerosis. J Clin Gastroenterol39:303–306PubMedCrossRefGoogle Scholar
  7. 7.
    Foroozan R, Buono LM, Sergott RC,Savino PJ (2002) Retrobulbar opticneuritis associated with infliximab.Arch Ophthalmol 120:985–987PubMedGoogle Scholar
  8. 8.
    Fox DA (2000) Cytokine blockade as anew strategy to treat rheumatoidarthritis. Inhibition of tumor necrosisfactor. Arch Intern Med 160:437–444PubMedCrossRefGoogle Scholar
  9. 9.
    Gupta G, Gelfand JM, Lewis JD (2005)Increased risk for demyelinating diseasesin patients with inflammatorybowel disease. Gastroenterology 129:1117–1120CrossRefGoogle Scholar
  10. 10.
    Hemmer B, Hartung HP (2007)Towards the development of rationaltherapies in multiple sclerosis: What ison the horizon? Ann Neurol 62:314–326PubMedCrossRefGoogle Scholar
  11. 11.
    Jarand J, Zochodne DW, Martin LO,Voll C (2006) Neurological complicationsof infliximab. J Rheumatol 33:1018–1020PubMedGoogle Scholar
  12. 12.
    Kelley RE (2006) Ischemic demyelination.Neurol Res 28:334–340PubMedCrossRefGoogle Scholar
  13. 13.
    Kim E, Edgar E, Isenhath S, Blauwelt A,Bourdette D, Whitham R (2008)Successful treatment of pyodermagangrenosum with a TNF-alphablocker in a subject with multiplesclerosis. Neurology 70(Suppl 1):A93Google Scholar
  14. 14.
    Kimura K, Hunter SF, Thollander MS,Loftus EV Jr, Melton LJ 3rd, O’BrienPC, Rodriguez M, Phillips SF (2000)Concurrence of inflammatory boweldisease and multiple sclerosis. MayoClin Proc 75:802–806Google Scholar
  15. 15.
    Kodama S, Davis M, Faustmann DL(2005) The therapeutic potential oftumor necrosis factor for autoimmunedisease: a mechanistically basedhypothesis. Cell Mol Lif Sci 62:1850–1862CrossRefGoogle Scholar
  16. 16.
    Magnano MD, Robinson WH, GenoveseMC (2004) Demyelination andinhibition of tumor necrosis factor(TNF). Clin Exp Rheumatol 22(5 Suppl35):S134–S140PubMedGoogle Scholar
  17. 17.
    Marotte H, Charrin JE, Miossec P(2002) Infliximab-induced asepticmeningitis. Lancet 359:1252Google Scholar
  18. 18.
    McDonald WI, Compston A, Edan G,Goodkin D, Hartung HP, Lublin FD,McFarland HF, Paty DW, Polman CH,Reingold SC, Sandberg-Wollheim M,Sibley W, Thompson A, van den NoortS, Weinshenker BY, Wolinsky JS (2001)Recommended diagnostic criteria formultiple sclerosis: guidelines from theInternational Panel on the diagnosis ofmultiple sclerosis. Ann Neurol 50:121–127PubMedCrossRefGoogle Scholar
  19. 19.
    Midgard R, Grønning M, Riise T, KvåleG, Nyland H (1996) Multiple sclerosisand chronic inflammatory diseases. Acase-control study. Acta Neurol Scand93:322–328PubMedCrossRefGoogle Scholar
  20. 20.
    Mohan N, Edwards ET, Cupps TR,Oliviero PJ, Sandberg G, Crayton H,Richert JR, Siegel JN (2001) Demyelinationoccuring during anti-tumornecrosis factor alpha therapy forinflammatory arthritides. ArthritisRheum 44:2862–2869Google Scholar
  21. 21.
    Quispel R, van der Worp HB, PruissenM, Schipper ME, Oldenburg B (2006)Fatal aseptic meningoencephalitisfollowing infliximab treatment for inflammatorybowel disease. Gut 55:1056PubMedCrossRefGoogle Scholar
  22. 22.
    Ramagopalan SV, Dyment DA, ValdarW, Herrera BM, Criscuoli M, Yee IM,Sadovnick AD, Ebers GC; CanadianCollaborative Study Group (2007)Autoimmune disease in families withmultiple sclerosis: a population-basedstudy. Lancet Neurol 6:604–610PubMedCrossRefGoogle Scholar
  23. 23.
    Ranges GE, Figari IS, Espevik T, PalladinoMA (1987) Inhibition of cytotoxicT cell development by transforminggrowth factor-beta and reversakl byrecombinant tumor necrosis factoralpha. J Exp Med 166:991–999PubMedCrossRefGoogle Scholar
  24. 24.
    Reidel MA, Stippich C, Heiland S,Storch-Hagenlocher B, Jansen O,Hähnel S (2003) Differentiation ofmultiple sclerosis plaques, subacutecerebral ischaemic infarcts, focalvasogenic oedema and lesions of subcorticalarteriosclerotic encephalopathyusing magnetisation transfer measurements.Neuroradiology 45:289–294PubMedGoogle Scholar
  25. 25.
    Selmaj KW, Raine CS (1988) Tumor necrosisfactor mediates myelin and oligodendrocytedamage in vitro. AnnNeurol 23:339–346Google Scholar
  26. 26.
    Selmaj KW, Raine CS (1995) Experimentalautoimmune encephalomyelitis:immunotherapy with anti-tumornecrosis factor antibodies and solubletumor necrosis factor receptors. Neurology45(Suppl 6):S44–S49PubMedGoogle Scholar
  27. 27.
    Selmaj KW (2000) Tumour necrosisfactor and anti-tumour necrosis factorapproach to inflammatory demyelinatingdiseases of the central nervous system.Ann Rheum Dis 59(Suppl I):i94–i102PubMedCrossRefGoogle Scholar
  28. 28.
    Shin IS, Baer AN, Kwon HJ, PapadopoulosEJ, Siegel JN (2006) Guillain-Barré and Miller Fisher syndromesoccurring with tumor necrosis factoralpha antogonist therapy. ArthritisRheum 54:1429–1434Google Scholar
  29. 29.
    Sicotte NL, Voskuhl RR (2001) Onset ofmultiple sclerosis associated with anti-TNF therapy. Neurology 57:1885–1888PubMedGoogle Scholar
  30. 30.
    Tan FU, Tellioğlu S, Aydin G,Erdemoğlu AK, Keles¸ I (2004) Ankylosingspondylitis and multiple sclerosisin a HLA-B27 negative patient. ActaNeurol Belg 104:169–172Google Scholar
  31. 31.
    Tanno M, Nakamura I, Kobayashi S,Kurihara K, Ito K (2006) New-onsetdemyelination induced by infliximabtherapy in two rheumatoid arthritispatients. Clin Rheumatol 25:929–933PubMedCrossRefGoogle Scholar
  32. 32.
    The Lenercept Multiple Sclerosis StudyGroup and the University of BritishColumbia MS/MRI Analysis Group(1999) TNF neutralization in multiplesclerosis: results of a randomized,placebo-controlled multicenter study.Neurology 53:457–465Google Scholar
  33. 33.
    Thomas CW Jr, Weinshenker BG, SandbornWJ (2004) Demyelination duringanti-tumor necrosis factor alpha therapywith infliximab for Crohn’s disease.Inflamm Bowel Dis 10:28–31PubMedCrossRefGoogle Scholar
  34. 34.
    Titelbaum DS, Degenhardt A, KinkelRP (2005) Anti-tumor necrosis factoralpha-associated Multiple Sclerosis.Am J Neuroradiol 26:1548–1550PubMedGoogle Scholar
  35. 35.
    Toussirot E, Pertuiset E, Martin A,Melac-Ducamp S, Alcalay M, Grardel B,Seror P, Perdriger A, Wendling D,Mulleman D, Beraneck L, Mariette X;Club Rheumatismes et Inflammation(2006) Association of rheumatoidarthritis with multiple sclerosis: reportof 14 cases and discussion of its significance.J Rheumatol 33:1027–1028PubMedGoogle Scholar
  36. 36.
    Van Oosten BW, Barkhof F, Truyen L,Boringa JB, Berteslmann FW, vonBolmberg BM, Woody JN, Hartung HP,Polman CH (1996) Increased MRIactivity and immune activation in twomultiple sclerosis patients treated withthe monoclonal anti-tumor necrosisfactor antibody cA2. Neurology 47:1531–1534PubMedGoogle Scholar
  37. 37.
    Yokota S, Geppert TD, Lipsky PI (1988)Enhancement of antigen-and mitogen-inducedhuman T lymphocyte proliferationby tumor necrosis factor.J Immunol 140:531–538PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2008

Authors and Affiliations

  • Alexander Winkelmann
    • 1
  • Robert Patejdl
    • 1
  • Sabine Wagner
    • 2
  • Reiner Benecke
    • 1
  • Uwe Klaus Zettl
    • 1
  1. 1.Dept. of NeurologyUniversity of RostockRostockGermany
  2. 2.Institute for Diagnostic and Interventionell RadiologyUniversity of RostockRostockGermany

Personalised recommendations