Skip to main content
SpringerLink
Log in

Concepts of Immune Therapy and Disease Management

  • Chapter
  • First Online:
Neuroimmunology

  • 1474 Accesses

Abstract

Autoimmune inflammatory disorders are often marked by subacute development of new or worsening symptoms. These relapses reflect active inflammation and should be promptly recognized for early treatment and optimization of chronic immunomodulating or immunosuppressing therapies to avoid disability accumulation over time. Detection of subclinical activity using paraclinical testing also warrants a change in treatment and should be part of the monitoring approach of most disorders. Differentiating pseudorelapses or fluctuating symptoms from true relapses is important for appropriate management. Depending on the disease, oral or intravenous corticosteroids at low or high dosages, intravenous immunoglobulin, and plasmapheresis can be used to halt the inflammatory process and increase the chances of tissue recovery. Optimal symptom management is essential to improve functional outcomes and to complement the beneficial effect of long-term maintenance therapies. Management is limited by the lack of evidence-based guidelines for the monitoring and treatment of most disorders, with the exception of multiple sclerosis. Because of the difficulty to perform randomized controlled trials in autoimmune neurology, future work should aim at increasing knowledge from real-world cohorts and optimizing monitoring tools of disease activity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lancaster E. Paraneoplastic disorders. Contin Lifelong Learn Neurol. 2017;23(6):1653–79.

    Article  Google Scholar 

  2. Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: State-of-the-art and emerging therapies. Nat Rev Neurol. 2014;10(9):493–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lancaster E. The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol. 2016;12(1):1–13.

    Article  PubMed  Google Scholar 

  4. Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018;378(2):169–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dalakas MC. Advances in the diagnosis, pathogenesis and treatment of CIDP. Nat Rev Neurol. 2011;7(9):507–17.

    Article  PubMed  Google Scholar 

  6. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. Lancet. 2014;383(9923):1155–67.

    Article  PubMed  Google Scholar 

  7. Wingerchuk DM, Frcp C, Pittock SJ, Lucchinetti CF, Lennon VA, Weinshenker BG. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 2007;68:603–5.

    Article  CAS  PubMed  Google Scholar 

  8. Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology. 2003;61:1528–32.

    Article  PubMed  Google Scholar 

  9. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Florance NR, Davis RL, Lam C, Szperka C, Zhou L, Ahmad S, et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol. 2009;66(1):11–8.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Joubert B, Chapelon-Abric C, Biard L, Saadoun D, Demeret S, Dormont D, et al. Association of prognostic factors and immunosuppressive treatment with long-term outcomes in neurosarcoidosis. JAMA Neurol. 2017;74(11):1336–44.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Chiò A, Cocito D, Bottacchi E, Buffa C, Leone M, Plano F, et al. Idiopathic chronic inflammatory demyelinating polyneuropathy: an epidemiological study in Italy. J Neurol Neurosurg Psychiatry. 2007;78(12):1349–53.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cutter G, Baier M, Rudick R, Cookfair D, Fischer J, John Petkau J, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain. 1999;122:871–82.

    Article  PubMed  Google Scholar 

  14. Isaac C, Li DK, Genton M, Jardine C, Grochowski E, Palmer M, et al. Multiple sclerosis: a serial study using MRI in relapsing patients. Neurology. 1988;38(10):1511–5.

    Article  CAS  PubMed  Google Scholar 

  15. Vincent A, Bien CG, Irani SR, Waters P. Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol. 2011;10(8):759–72.

    Article  CAS  PubMed  Google Scholar 

  16. Broadley J, Seneviratne U, Beech P, Buzzard K, Butzkueven H, O’Brien T, et al. Prognosticating autoimmune encephalitis: a systematic review. J Autoimmun. 2019;96:24–34.

    Article  PubMed  Google Scholar 

  17. Hakansson I, Tisell A, Cassel P, Blennow K, Zetterberg H, Lundberg P, et al. Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing – remitting multiple sclerosis. Eur J Neurol. 2017;24:703–12.

    Google Scholar 

  18. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335(1):2–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fox RJ, Kinkel RP. High-dose methylprednisolone to treat multiple sclerosis. In: Cohen JA, Rudick RA, editors. Multiple sclerosis therapeutics. Cambridge: Cambridge University Press; 2011. p. 418–35.

    Chapter  Google Scholar 

  20. Smoak KA, Cidlowski JA. Mechanisms of glucocorticoid receptor signaling during inflammation. Mech Ageing Dev. 2004;125(10–11 SPEC. ISS):697–706.

    Article  CAS  PubMed  Google Scholar 

  21. Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain. 2008;131(11):3072–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Citterio A, LaMantia L, Ciucci G, Candelise L, Brusaferri F, Midgard R, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev. 2013;(4):CD001331.

    Google Scholar 

  23. Barnes D, Hughes RAC, Morris RW, Wade-Jones O, Brown P, Britton T, et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet. 1997;349(9056):902–6.

    Article  CAS  PubMed  Google Scholar 

  24. Thomson A, Kennard C, Swash M, Summers B, Yuill G, Sheperd D, et al. Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology. 1989;39(July):969–72.

    Article  Google Scholar 

  25. Milligan NM, Newcombe R, Compston DA. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects. J Neurol Neurosurg Psychiatry. 1987;50(5):511–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sellebjerg F, Frederiksen JL, Nielsen PM, Olesen J. Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS. Neurology. 1998;51(2):529–34.

    Article  CAS  PubMed  Google Scholar 

  27. Abboud H, Petrak A, Mealy M, Sasidharan S, Siddique L, Levy M. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016;22(2):185–92.

    Article  CAS  PubMed  Google Scholar 

  28. Sherman E, Han MH. Acute and chronic management of neuromyelitis optica spectrum disorder. Curr Treat Options Neurol. 2015;17:48.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Greenberg BM, Thomas KP, Krishnan C, Kaplin AI, Calabresi PA, Kerr DA. Idiopathic transverse myelitis: corticosteroids, plasma exchange, or cyclophosphamide. Neurology. 2007;68(19):1614–7.

    Article  CAS  PubMed  Google Scholar 

  30. Beck RW, Cleary PA, Anderson MMJ, Keltner JL, Shults WT, Kaufman DI, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992;326(9):581–8.

    Article  CAS  PubMed  Google Scholar 

  31. Clark KEN, Isenberg DA. A review of inflammatory idiopathic myopathy focusing on polymyositis. Eur J Neurol. 2018;25(1):13–23.

    Article  CAS  PubMed  Google Scholar 

  32. Hughes R, Bensa S, Willison H, Van den Bergh P, Comi G, Illa I, et al. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 2001;50(2):195–201.

    Article  CAS  PubMed  Google Scholar 

  33. Jinka M, Chaudhry V. Treatment of multifocal motor neuropathy. Curr Treat Options Neurol. 2014;16(2):269.

    Article  PubMed  Google Scholar 

  34. Luemann JD, Nimmerjahn F, Dalakas MC. Intravenous immunoglobulin in neurology-mode of action and clinical efficacy. Nat Rev Neurol. 2015;11(2):80–9.

    Article  CAS  Google Scholar 

  35. Dalakas MC. Mechanism of action of intravenous immunoglobulin and therapeutic considerations in the treatment of autoimmune neurologic diseases. Neurology. 1998;51(6 Suppl 5):S2–8.

    Article  CAS  PubMed  Google Scholar 

  36. Patwa HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT. Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders. Neurology. 2012;78:1009–15.

    Article  CAS  PubMed  Google Scholar 

  37. Kleyweg RP, van der Meche FG, Meulstee J. Treatment of Guillain-Barre syndrome with high-dose gammaglobulin. Neurology. 1988;38(10):1639–41.

    Article  CAS  PubMed  Google Scholar 

  38. Hughes RAC, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, et al. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomized placebo-controlled trial. Lancet Neurol. 2008;7(2):136–44.

    Article  CAS  PubMed  Google Scholar 

  39. Leger JM, Chassande B, Musset L, Meininger V, Bouche P, Baumann N. Intravenous immunoglobulin therapy in multifocal motor neuropathy: a double-blind, placebo-controlled study. Brain. 2001;124(Pt 1):145–53.

    Article  CAS  PubMed  Google Scholar 

  40. Morozumi S, Kawagashira Y, Iijima M, Koike H, Hattori N, Katsuno M, et al. Intravenous immunoglobulin treatment for painful sensory neuropathy associated with Sjogren’s syndrome. J Neurol Sci. 2009;279(1–2):57–61.

    Article  CAS  PubMed  Google Scholar 

  41. Tavee JO, Karwa K, Ahmed Z, Thompson N, Parambil J, Culver DA. Sarcoidosis-associated small fiber neuropathy in a large cohort: clinical aspects and response to IVIG and anti-TNF alpha treatment. Respir Med. 2017;126:135–8.

    Article  PubMed  Google Scholar 

  42. Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev. 2012;(12):Art. No.: CD002277.

    Google Scholar 

  43. Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev. 2011;(2):Art. No.: CD003279.

    Google Scholar 

  44. Dalakas MC, Illa I, Dambrosia JM, Soueidan SA, Stein DP, Otero C, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med. 1993;329(27):1993–2000.

    Article  CAS  PubMed  Google Scholar 

  45. Nosadini M, Mohammad SS, Ramanathan S, Brilot F, Dale RC. Immune therapy in autoimmune encephalitis: a systematic review. Expert Rev Neurother. 2015;15(12):1391–419.

    Article  CAS  PubMed  Google Scholar 

  46. Dalakas MC, Fujii M, Li M, Lutfi B, Kyhos J, McElroy B. High-dose intravenous immune globulin for stiff-person syndrome. N Engl J Med. 2001;345(26):1870–6.

    Article  CAS  PubMed  Google Scholar 

  47. Bonnan M, Valentino R, Debeugny S, Merle H, Ferge J-L, Mehdaoui H, et al. Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiatry. 2018;89(4):346–51.

    Article  PubMed  Google Scholar 

  48. Basic-Jukic N, Kes P, Glavas-Boras S, Brunetta B, Bubic-Filipi L, Puretic Z. Complications of therapeutic plasma exchange: experience with 4857 treatments. Ther Apher Dial. 2005;9(5):391–5.

    Article  PubMed  Google Scholar 

  49. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999 Sep;53(5):1107–14.

    Article  CAS  PubMed  Google Scholar 

  50. Tselis A, Perumal J, Caon C, Hreha S, Ching W, Din M, et al. Treatment of corticosteroid refractory optic neuritis in multiple sclerosis patients with intravenous immunoglobulin. Eur J Neurol. 2008;15(11):1163–7.

    Article  CAS  PubMed  Google Scholar 

  51. Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler. 2014;20(4):501–4.

    Article  CAS  PubMed  Google Scholar 

  52. Reeves HM, Winters JL. The mechanisms of action of plasma exchange. Br J Haematol. 2014;164(3):342–51.

    Article  CAS  PubMed  Google Scholar 

  53. Hughes RAC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2014;(9):Art. No.: CD002063.

    Google Scholar 

  54. Dyck PJ, Litchy WJ, Kratz KM, Suarez GA, Low PA, Pineda AA, et al. A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 1994;36(6):838–45.

    Article  CAS  PubMed  Google Scholar 

  55. Barth D, Nabavi Nouri M, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011;76(23):2017–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gwathmey K, Balogun R, Burns T. Neurologic indications for therapeutic plasma exchange: 2013 update. J Clin Apher. 2013;29:211–9.

    Article  Google Scholar 

  57. Newsom-Davis J. Therapy in myasthenia gravis and Lambert-Eaton myasthenic syndrome. Semin Neurol. 2003;23(2):191–8.

    Article  PubMed  Google Scholar 

  58. Weinshenker BG, O’Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999;46(6):878–86.

    Article  CAS  PubMed  Google Scholar 

  59. Weinshenker BG, Wingerchuk DM, Vukusic S, Linbo L, Pittock SJ, Lucchinetti CF, et al. Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol. 2006 Mar;59(3):566–9.

    Article  CAS  PubMed  Google Scholar 

  60. Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 2015 Feb;72(2):152–8.

    Article  PubMed  Google Scholar 

  61. Sormani MP, Muraro PA, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler. 2017;23(2):201–4.

    Article  PubMed  Google Scholar 

  62. Brown JWL, Coles A, Horakova D, Havrdova E, Izquierdo G, Prat A, et al. Association of Initial Disease-Modifying Therapy with later conversion to secondary progressive multiple sclerosis. JAMA. 2019;321(2):175–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Adrichem ME, Eftimov F, van Schaik IN. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy, a time to start and a time to stop. J Peripher Nerv Syst. 2016;21(3):121–7.

    Article  CAS  PubMed  Google Scholar 

  64. Lunn M, Ellis L, Hadden R, Rajabally Y, Winer J, Reilly MM. A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. J Peripher Nerv Syst. 2016;21(1):33–7.

    Article  CAS  PubMed  Google Scholar 

  65. Disanto G, Zecca C, MacLachlan S, Sacco R, Handunnetthi L, Meier UC, et al. Prodromal symptoms of multiple sclerosis in primary care. Ann Neurol. 2018;83(6):1162–73.

    Article  PubMed  Google Scholar 

  66. Macaron G, Cohen JA. Integrating multiple sclerosis guidelines into practice. Lancet Neurol. 2018;17(8):658–60.

    Article  PubMed  Google Scholar 

  67. Learmonth YC, Dlugonski D, Pilutti LA, Sandroff BM, Klaren R, Motl RW. Psychometric properties of the fatigue severity scale and the modified fatigue impact scale. J Neurol Sci. 2013;331(1–2):102–7.

    Article  CAS  PubMed  Google Scholar 

  68. Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Novakova L, Zetterberg H, Sundstrom P, Axelsson M, Khademi M, Gunnarsson M, et al. Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology. 2017;89(22):2230–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Mariotto S, Farinazzo A, Magliozzi R, Alberti D, Monaco S, Ferrari S. Serum and cerebrospinal neurofilament light chain levels in patients with acquired peripheral neuropathies. J Peripher Nerv Syst. 2018;23(3):174–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Gabrielle Macaron

  2. Department of Neurology, University of Mississippi Medical Center, Jackson, MS, USA

    Mary Alissa Willis

Authors
  1. Gabrielle Macaron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary Alissa Willis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mary Alissa Willis .

Editor information

Editors and Affiliations

  1. University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Amanda L. Piquet

  2. University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Enrique Alvarez

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Macaron, G., Willis, M.A. (2021). Concepts of Immune Therapy and Disease Management. In: Piquet, A.L., Alvarez, E. (eds) Neuroimmunology. Springer, Cham. https://doi.org/10.1007/978-3-030-61883-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-61883-4_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-61882-7

  • Online ISBN: 978-3-030-61883-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation