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Neurocritical Care

, Volume 12, Issue 1, pp 132–143 | Cite as

Immunomodulatory Therapies in Neurologic Critical Care

  • Logan M. McDaneld
  • Jeremy D. Fields
  • Dennis N. Bourdette
  • Anish BhardwajEmail author
Review

Abstract

Introduction

Neurologic disorders with autoimmune dysregulation are commonly encountered in the critical care setting. Frequently encountered diseases include Guillain–Barré syndrome (GBS), myasthenia gravis, multiple sclerosis, acute demyelinating encephalomyelitis, and encephalitides. Immunomodulatory therapies, including high-dose corticosteroids, plasmapheresis, and intravenous immunoglobulins, are the cornerstone of the treatment of these diseases. Here we review the efficacy and side effects of immunomodulatory therapies commonly utilized in critically ill neurologic patients in the intensive care setting.

Methods

Search of Medline, Cochrane databases, and manual review of article bibliographies.

Results

The efficacy of high-dose corticosteroids, plasmapheresis, and intravenous immunoglobulins have been studied extensively in GBS, myasthenia gravis, and demyelinating disorders such as multiple sclerosis and acute demyelinating encephalomyelitis. For these diseases, however, the duration of treatment, dosing regimens, and choices among different therapeutic modalities remain controversial. For many of the other diseases (e.g., encephalitis and status epilepticus of autoimmune etiology) discussed in this review, evidence is limited to small case series.

Conclusions

There is good evidence for the efficacy and tolerability of immunomodulatory therapies in GBS, myasthenia gravis, and acute central nervous system demyelination, though data to establish superiority of one therapeutic regimen over another remains lacking. For most other conditions, the data for immunomodulatory therapies are limited, and further research is required.

Keywords

Immunomodulation Corticosteroids Plasmapheresis Immunoglobulin Cyclophosphamide 

Notes

Acknowledgments

Dr. Bhardwaj is supported in part by the U.S. Public Health Service National Institutes of Health Grant NS046379.

References

  1. 1.
    Broessner G, Helbok R, Lackner P, et al. Survival and long-term functional outcome in 1,155 consecutive neurocritical care patients. Crit Care Med. 2007;35:2025–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Gomes JA, Stevens RD, Lewin JJ III, Mirski MA, Bhardwaj A. Glucocorticoid therapy in neurologic critical care. Crit Care Med. 2005;33:1214–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Parker BJ, Bruce IN. High dose methylprednisolone therapy for the treatment of severe systemic lupus erythematosus. Lupus. 2007;16:387–93.PubMedCrossRefGoogle Scholar
  4. 4.
    Filippini G, Brusaferri F, Sibley WA, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev. 2000;001331.Google Scholar
  5. 5.
    Lindberg C, Andersen O, Lefvert AK. Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study. Acta Neurol Scand. 1998;97:370–3.PubMedCrossRefGoogle Scholar
  6. 6.
    Lehmann HC, Hartung HP, Hetzel GR, Stuve O, Kieseier BC. Plasma exchange in neuroimmunological disorders: Part 1: Rationale and treatment of inflammatory central nervous system disorders. Arch Neurol. 2006;63:930–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Mokrzycki MH, Kaplan AA. Therapeutic plasma exchange: complications and management. Am J Kidney Dis. 1994;23:817–27.PubMedGoogle Scholar
  8. 8.
    Keller AJ, Urbaniak SJ. Intensive plasma exchange on the cell separator: effects on serum immunoglobulins and complement components. Br J Haematol. 1978;38:531–40.PubMedCrossRefGoogle Scholar
  9. 9.
    Yeh JH, Chiu HC. Plasmapheresis-related hypotension. Artif Organs. 2000;24:705–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Gold R, Stangel M, Dalakas MC. Drug Insight: the use of intravenous immunoglobulin in neurology—therapeutic considerations and practical issues. Nat Clin Pract Neurol. 2007;3:36–44.PubMedCrossRefGoogle Scholar
  11. 11.
    Kaveri SV, Lacroix-Desmazes S, Bayry J. The antiinflammatory IgG. N Engl J Med. 2008;359:307–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med. 2001;345:747–55.PubMedCrossRefGoogle Scholar
  13. 13.
    Paran D, Herishanu Y, Elkayam O, Shopin L, Ben-Ami R. Venous and arterial thrombosis following administration of intravenous immunoglobulins. [see comment]. Blood Coagul Fibrinol. 2005;16:313–8.CrossRefGoogle Scholar
  14. 14.
    Ballow M. Safety of IGIV therapy and infusion-related adverse events. Immunol Res. 2007;38:122–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol. 2005;29:173–84.PubMedCrossRefGoogle Scholar
  16. 16.
    Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain–Barre syndrome [see comment]. Ann Neurol. 1990;27:S21–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Hughes RA, Rees JH. Clinical and epidemiologic features of Guillain–Barre syndrome. J Infect Dis. 1997;176:S92–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Bosch PE, Smith BE. Disorders of peripheral nerves. In: Neurology in clinical practice. 5th ed. Philadelphia: Butterworth-Heinemann; 2004. p. 2336–2345.Google Scholar
  19. 19.
    Zochodne DW. Autonomic involvement in Guillain–Barre syndrome: a review. Muscle Nerve. 1994;17:1145–55.PubMedCrossRefGoogle Scholar
  20. 20.
    Bernsen RA, de Jager AE, Schmitz PI, van der Meche FG. Residual physical outcome and daily living 3 to 6 years after Guillain–Barre syndrome. Neurology. 1999;53:409–10.PubMedGoogle Scholar
  21. 21.
    van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain–Barre syndrome [see comment]. Lancet Neurol. 2008;7:939–50.PubMedCrossRefGoogle Scholar
  22. 22.
    Willison HJ, Yuki N. Peripheral neuropathies and anti-glycolipid antibodies. Brain. 2002;125:2591–625.PubMedCrossRefGoogle Scholar
  23. 23.
    Chowdhury D, Arora A. Axonal Guillain–Barre syndrome: a critical review. Acta Neurol Scand. 2001;103:267–77.PubMedCrossRefGoogle Scholar
  24. 24.
    Hafer-Macko CE, Sheikh KA, Li CY, et al. Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy. Ann Neurol. 1996;39:625–35.PubMedCrossRefGoogle Scholar
  25. 25.
    Hafer-Macko C, Hsieh ST, Li CY, et al. Acute motor axonal neuropathy: an antibody-mediated attack on axolemma. Ann Neurol. 1996;40:635–44.PubMedCrossRefGoogle Scholar
  26. 26.
    The Guillain–Barre syndrome Study Group. Plasmapheresis and acute Guillain–Barre syndrome. Neurology. 1985;35:1096–104.Google Scholar
  27. 27.
    French Cooperative Group on Plasma Exchange in Guillain–Barre syndrome. Efficiency of plasma exchange in Guillain–Barre syndrome: role of replacement fluids. Ann Neurol. 1987;22:753–61.Google Scholar
  28. 28.
    Raphael JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain–Barre syndrome [update of Cochrane Database Syst Rev. 2001;(2):CD001798; PMID: 11406009]. Cochrane Database Syst Rev. 2002;001798.Google Scholar
  29. 29.
    van der Meche FG, Schmitz PI. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain–Barre syndrome. Dutch Guillain–Barre Study Group. N Engl J Med. 1992;326:1123–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Hughes RA, Raphael JC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain–Barre syndrome [update of Cochrane Database Syst Rev. 2004;(1):CD002063; PMID: 14973982]. Cochrane Database Syst Rev. 2006;002063.Google Scholar
  31. 31.
    Plasma Exchange/Sandoglobulin Guillain–Barre Syndrome Trial Group. Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain–Barre syndrome. Lancet. 1997;349:225–30.Google Scholar
  32. 32.
    Hughes RA, Swan AV, van Koningsveld R, van Doorn PA. Corticosteroids for Guillain–Barre syndrome [update of Cochrane Database Syst Rev. 2000;(3):CD001446; PMID: 10908498]. Cochrane Database Syst Rev. 2006;001446.Google Scholar
  33. 33.
    Hughes RA, Wijdicks EF, Barohn R, et al. Practice parameter: immunotherapy for Guillain–Barre syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003;61:736–40.PubMedGoogle Scholar
  34. 34.
    Barohn RJ, Kissel JT, Warmolts JR, Mendell JR. Chronic inflammatory demyelinating polyradiculoneuropathy. Clinical characteristics, course, and recommendations for diagnostic criteria. Arch Neurol. 1989;46:878–84.PubMedGoogle Scholar
  35. 35.
    McCombe PA, Pollard JD, McLeod JG. Chronic inflammatory demyelinating polyradiculoneuropathy. A clinical and electrophysiological study of 92 cases. Brain. 1987;110:1617–30.PubMedCrossRefGoogle Scholar
  36. 36.
    Dyck PJ, O’Brien PC, Oviatt KF, et al. Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann Neurol. 1982;11:136–41.PubMedCrossRefGoogle Scholar
  37. 37.
    Dyck PJ, Daube J, O’Brien P, et al. Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy. N Engl J Med. 1986;314:461–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Hahn AF, Bolton CF, Pillay N, et al. Plasma-exchange therapy in chronic inflammatory demyelinating polyneuropathy. A double-blind, sham-controlled, cross-over study. Brain. 1996;119:1055–66.PubMedCrossRefGoogle Scholar
  39. 39.
    Eftimov F, Winer JB, Vermeulen M, de Haan R, van Schaik IN. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy [update of Cochrane Database Syst Rev. 2002;(2):CD001797; PMID: 12076423]. Cochrane Database Syst Rev. 2009;001797.Google Scholar
  40. 40.
    Dyck PJ, Litchy WJ, Kratz KM, et al. A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 1994;36:838–45.PubMedCrossRefGoogle Scholar
  41. 41.
    Hughes RA, Swan AV, van Doorn PA. Cytotoxic drugs and interferons for chronic inflammatory demyelinating polyradiculoneuropathy [update of Cochrane Database Syst Rev. 2003;(1):CD003280; PMID: 12535467]. Cochrane Database Syst Rev. 2004;003280.Google Scholar
  42. 42.
    Kelly JJ Jr, Kyle RA, O’Brien PC, Dyck PJ. Prevalence of monoclonal protein in peripheral neuropathy. Neurology. 1981;31:1480–3.PubMedGoogle Scholar
  43. 43.
    Lunn MP, Nobile-Orazio E. Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies [update of Cochrane Database Syst Rev. 2003;(1):CD002827; PMID: 12535440]. Cochrane Database Syst Rev. 2006;002827.Google Scholar
  44. 44.
    Dalakas MC, Rakocevic G, Salajegheh M, et al. Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy. Ann Neurol. 2009;65:286–93.PubMedCrossRefGoogle Scholar
  45. 45.
    Allen D, Lunn MP, Niermeijer J, Nobile-Orazio E. Treatment for IgG and IgA paraproteinaemic neuropathy. Cochrane Database Syst Rev. 2007;005376.Google Scholar
  46. 46.
    van Schaik IN, van den Berg LH, de Haan R, Vermeulen M. Intravenous immunoglobulin for multifocal motor neuropathy. Cochrane Database Syst Rev. 2005;004429.Google Scholar
  47. 47.
    Umapathi T, Hughes RA, Nobile-Orazio E, Leger JM. Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy [update of Cochrane Database Syst Rev. 2005;(3):CD003217; PMID: 16034892]. Cochrane Database Syst Rev. 2009;003217.Google Scholar
  48. 48.
    Vrancken AF, Hughes RA, Said G, Wokke JH, Notermans NC. Immunosuppressive treatment for non-systemic vasculitic neuropathy. Cochrane Database Syst Rev. 2007;006050.Google Scholar
  49. 49.
    Ahmed S, Kirmani JF, Janjua N, et al. An update on myasthenic crisis. Curr Treat Opt Neurol. 2005;7:129–41.CrossRefGoogle Scholar
  50. 50.
    Grob D, Brunner N, Namba T, Pagala M. Lifetime course of myasthenia gravis. Muscle Nerve. 2008;37:141–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Lindstrom JM. Acetylcholine receptors and myasthenia. Muscle Nerve. 2000;23:453–77.PubMedCrossRefGoogle Scholar
  52. 52.
    Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. Lancet. 2001;357:2122–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Tzartos S, Hochschwender S, Vasquez P, Lindstrom J. Passive transfer of experimental autoimmune myasthenia gravis by monoclonal antibodies to the main immunogenic region of the acetylcholine receptor. J Neuroimmunol. 1987;15:185–94.PubMedCrossRefGoogle Scholar
  54. 54.
    McConville J, Farrugia ME, Beeson D, et al. Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol. 2004;55:580–4.PubMedCrossRefGoogle Scholar
  55. 55.
    Berrouschot J, Baumann I, Kalischewski P, Sterker M, Schneider D. Therapy of myasthenic crisis [see comment]. Crit Care Med. 1997;25:1228–35.PubMedCrossRefGoogle Scholar
  56. 56.
    Schneider-Gold C, Gajdos P, Toyka KV, Hohlfeld RR. Corticosteroids for myasthenia gravis. Cochrane Database Syst Rev. 2005;002828.Google Scholar
  57. 57.
    Bromberg MB, Carter O. Corticosteroid use in the treatment of neuromuscular disorders: empirical and evidence-based data. Muscle Nerve. 2004;30:20–37.PubMedCrossRefGoogle Scholar
  58. 58.
    Jani-Acsadi A, Lisak RP. Myasthenic crisis: guidelines for prevention and treatment. J Neurol Sci. 2007;261:127–33.PubMedCrossRefGoogle Scholar
  59. 59.
    Antozzi C, Gemma M, Regi B, et al. A short plasma exchange protocol is effective in severe myasthenia gravis. J Neurol. 1991;238:103–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Yeh JH, Chiu HC. Plasmapheresis in myasthenia gravis. A comparative study of daily versus alternately daily schedule. Acta Neurol Scand. 1999;99:147–51.PubMedCrossRefGoogle Scholar
  61. 61.
    Weinstein R. Therapeutic apheresis in neurological disorders. J Clin Apheresis. 2000;15:74–128.PubMedCrossRefGoogle Scholar
  62. 62.
    Richman DP, Agius MA. Treatment of autoimmune myasthenia gravis [see comment]. Neurology. 2003;61:1652–61.PubMedGoogle Scholar
  63. 63.
    Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial. Neurology. 2007;68:837–41.PubMedCrossRefGoogle Scholar
  64. 64.
    Gajdos P, Chevret S, Clair B, Tranchant C, Chastang C. Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group. Ann Neurol. 1997;41:789–96.PubMedCrossRefGoogle Scholar
  65. 65.
    Gajdos P, Chevret S, Toyka K. Intravenous immunoglobulin for myasthenia gravis [update in Cochrane Database Syst Rev. 2008;(1):CD002277; PMID: 18254004][update of Cochrane Database Syst Rev. 2003;(2):CD002277; PMID: 12804431]. Cochrane Database Syst Rev. 2006;002277.Google Scholar
  66. 66.
    Shibuya N, Sato T, Osame M, Takegami T, Doi S, Kawanami S. Immunoadsorption therapy for myasthenia gravis. J Neurol Neurosurg Psychiatry. 1994;57:578–81.PubMedCrossRefGoogle Scholar
  67. 67.
    Weiner HL, Cohen JA. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects. Multiple Sclerosis. 2002;8:142–54.PubMedCrossRefGoogle Scholar
  68. 68.
    Tenembaum S, Chitnis T, Ness J, Hahn JS, International Pediatric MS Study G. Acute disseminated encephalomyelitis. Neurology. 2007;68:S23–36.PubMedCrossRefGoogle Scholar
  69. 69.
    Sorensen PS, Mellgren SI, Svenningsson A, et al. NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial. Lancet Neurol. 2009;8:519–29.PubMedCrossRefGoogle Scholar
  70. 70.
    Schwarz S, Mohr A, Knauth M, Wildemann B, Storch-Hagenlocher B. Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology. 2001;56:1313–8.PubMedGoogle Scholar
  71. 71.
    Sorensen PS, Haas J, Sellebjerg F, Olsson T, Ravnborg M, TARIMS Study G. IV immunoglobulins as add-on treatment to methylprednisolone for acute relapses in MS. Neurology. 2004;63:2028–33.PubMedGoogle Scholar
  72. 72.
    Tenembaum S, Chamoles N, Fejerman N. Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology. 2002;59:1224–31.PubMedGoogle Scholar
  73. 73.
    Jacquerye P, Ossemann M, Laloux P, Dive A, De Coene B. Acute fulminant multiple sclerosis and plasma exchange. Eur Neurol. 1999;41:174–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Mao-Draayer Y, Braff S, Pendlebury W, Panitch H. Treatment of steroid-unresponsive tumefactive demyelinating disease with plasma exchange. Neurology. 2002;59:1074–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Rodriguez M, Karnes WE, Bartleson JD, Pineda AA. Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology. 1993;43:1100–4.PubMedGoogle Scholar
  76. 76.
    RamachandranNair R, Parameswaran M, Girija AS. Acute disseminated encephalomyelitis treated with plasmapheresis. Singapore Med J. 2005;46:561–3.PubMedGoogle Scholar
  77. 77.
    Kanter DS, Horensky D, Sperling RA, Kaplan JD, Malachowski ME, Churchill WH Jr. Plasmapheresis in fulminant acute disseminated encephalomyelitis. Neurology. 1995;45:824–7.PubMedGoogle Scholar
  78. 78.
    Ryan LJ, Bowman R, Zantek ND, et al. Use of therapeutic plasma exchange in the management of acute hemorrhagic leukoencephalitis: a case report and review of the literature. Transfusion. 2007;47:981–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Weiner HL, Dau PC, Khatri BO, et al. Double-blind study of true vs. sham plasma exchange in patients treated with immunosuppression for acute attacks of multiple sclerosis. Neurology. 1989;39:1143–9.PubMedGoogle Scholar
  80. 80.
    Weinshenker BG, O’Brien PC, Petterson TM, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999;46:878–86.PubMedCrossRefGoogle Scholar
  81. 81.
    Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology. 2002;58:143–6.PubMedGoogle Scholar
  82. 82.
    Nishikawa M, Ichiyama T, Hayashi T, Ouchi K, Furukawa S. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. Pediatr Neurol. 1999;21:583–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Kleiman M, Brunquell P. Acute disseminated encephalomyelitis: response to intravenous immunoglobulin. J Child Neurol. 1995;10:481–3.PubMedCrossRefGoogle Scholar
  84. 84.
    Pradhan S, Gupta RP, Shashank S, Pandey N. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. J Neurol Sci. 1999;165:56–61.PubMedCrossRefGoogle Scholar
  85. 85.
    Hahn JS, Siegler DJ, Enzmann D. Intravenous gammaglobulin therapy in recurrent acute disseminated encephalomyelitis. Neurology. 1996;46:1173–4.PubMedGoogle Scholar
  86. 86.
    Sahlas DJ, Miller SP, Guerin M, Veilleux M, Francis G. Treatment of acute disseminated encephalomyelitis with intravenous immunoglobulin. Neurology. 2000;54:1370–2.PubMedGoogle Scholar
  87. 87.
    Finsterer J, Grass R, Stollberger C, Mamoli B. Immunoglobulins in acute, parainfectious, disseminated encephalo-myelitis. Clin Neuropharmacol. 1998;21:258–61.PubMedGoogle Scholar
  88. 88.
    Markus R, Brew BJ, Turner J, Pell M. Successful outcome with aggressive treatment of acute haemorrhagic leukoencephalitis. J Neurol Neurosurg Psychiatry. 1997;63:551.PubMedCrossRefGoogle Scholar
  89. 89.
    Marchioni E, Marinou-Aktipi K, Uggetti C, et al. Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis. J Neurol. 2002;249:100–4.PubMedCrossRefGoogle Scholar
  90. 90.
    Fu DC, Montgomery JR. High-dose, rapid-infusion IVIG in postvaccination acute disseminated encephalomyelitis. Neurology. 2008;71:294–5.PubMedCrossRefGoogle Scholar
  91. 91.
    Lu RP, Keilson G. Combination regimen of methylprednisolone, IV immunoglobulin, and plasmapheresis early in the treatment of acute disseminated encephalomyelitis. J Clin Apheresis. 2006;21:260–5.PubMedCrossRefGoogle Scholar
  92. 92.
    Shahar E, Andraus J, Savitzki D, Pilar G, Zelnik N. Outcome of severe encephalomyelitis in children: effect of high-dose methylprednisolone and immunoglobulins. J Child Neurol. 2002;17:810–4.PubMedCrossRefGoogle Scholar
  93. 93.
    Ravaglia S, Piccolo G, Ceroni M, et al. Severe steroid-resistant post-infectious encephalomyelitis: general features and effects of IVIg. J Neurol. 2007;254:1518–23.PubMedCrossRefGoogle Scholar
  94. 94.
    Visser LH, Beekman R, Tijssen CC, et al. A randomized, double-blind, placebo-controlled pilot study of i.v. immune globulins in combination with i.v. methylprednisolone in the treatment of relapses in patients with MS. Multiple Sclerosis. 2004;10:89–91.PubMedCrossRefGoogle Scholar
  95. 95.
    Kanaheswari Y, Baizura J, Paeds M, Zulfiqar A. Intravenous immunoglobulin in the treatment of acute disseminated encephalomyelitis. Med J Malaysia. 2004;59:103–7.PubMedGoogle Scholar
  96. 96.
    Kimiskidis V, Sakellari I, Tsimourtou V, et al. Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome. Multiple Sclerosis. 2008;14:278–83.PubMedCrossRefGoogle Scholar
  97. 97.
    Hartung HP, Gonsette R, Konig N, Kwiecinski H, Guseo A, Morrissey SP, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet. 2002;360:2018–25.PubMedCrossRefGoogle Scholar
  98. 98.
    Martinelli Boneschi F, Rovaris M, Capra R, Comi G. Mitoxantrone for multiple sclerosis. Cochrane Database Syst Rev. 2005;002127.Google Scholar
  99. 99.
    Gonsette RE. Mitoxantrone in progressive multiple sclerosis: when and how to treat? J Neurol Sci. 2003;206:203–8.PubMedCrossRefGoogle Scholar
  100. 100.
    Boster A, Edan G, Frohman E, Javed A, Stuve O, Tselis A, et al. Multiple Sclerosis Clinical Research Center, Department of Neurology, Wayne State University School of Medicine. Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician. Lancet Neurol. 2008;7:173–83.PubMedCrossRefGoogle Scholar
  101. 101.
    Hauser SL, Dawson DM, Lehrich JR, et al. Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med. 1983;308:173–80.PubMedCrossRefGoogle Scholar
  102. 102.
    Likosky WH, Fireman B, Elmore R, et al. Intense immunosuppression in chronic progressive multiple sclerosis: the Kaiser study. Journal of Neurol Neurosurg Psychiatry. 1991;54:1055–60.CrossRefGoogle Scholar
  103. 103.
    The Canadian Cooperative Multiple Sclerosis Study Group. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet. 1991;337:441–6.Google Scholar
  104. 104.
    Gonsette RE, Demonty L, Delmotte P. Intensive immunosuppression with cyclophosphamide in multiple sclerosis. Follow up of 110 patients for 2–6 years. J Neurol. 1977;214:173–81.PubMedCrossRefGoogle Scholar
  105. 105.
    Weinstock-Guttman B, Kinkel RP, Cohen JA, et al. Treatment of fulminant multiple sclerosis with intravenous cyclophosphamide. Neurologist. 1997;3:178–85.CrossRefGoogle Scholar
  106. 106.
    Khan OA, Zvartau-Hind M, Caon C, et al. Effect of monthly intravenous cyclophosphamide in rapidly deteriorating multiple sclerosis patients resistant to conventional therapy. Multiple Sclerosis. 2001;7:185–8.PubMedGoogle Scholar
  107. 107.
    Patti F, Cataldi ML, Nicoletti F, Reggio E, Nicoletti A, Reggio A. Combination of cyclophosphamide and interferon-beta halts progression in patients with rapidly transitional multiple sclerosis. J Neurol Neurosurg Psychiatry. 2001;71:404–7.PubMedCrossRefGoogle Scholar
  108. 108.
    Gladstone DE, Zamkoff KW, Krupp L, et al. High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis. Arch Neurol. 2006;63:1388–93.PubMedCrossRefGoogle Scholar
  109. 109.
    Blanco Y, Saiz A, Carreras E, Graus F. Autologous haematopoietic-stem-cell transplantation for multiple sclerosis. Lancet Neurol. 2005;4:54–63.PubMedCrossRefGoogle Scholar
  110. 110.
    Fassas A, Anagnostopoulos A, Kazis A, et al. Autologous stem cell transplantation in progressive multiple sclerosis—an interim analysis of efficacy. J Clin Immunol. 2000;20:24–30.PubMedCrossRefGoogle Scholar
  111. 111.
    Fassas A, Passweg JR, Anagnostopoulos A, Kazis A, Kozak T, Havrdova E, et al. Autoimmune Disease Working Party of the EBMT (European Group for Blood and Marrow Transplantation). Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088–97.PubMedCrossRefGoogle Scholar
  112. 112.
    Saiz A, Blanco Y, Carreras E, et al. Clinical and MRI outcome after autologous hematopoietic stem cell transplantation in MS. Neurology. 2004;62:282–4.PubMedGoogle Scholar
  113. 113.
    van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids for acute bacterial meningitis [see comment] [update of Cochrane Database Syst Rev. 2003;(3):CD004405; PMID: 12918010]. Cochrane Database Syst Rev. 2007;004405.Google Scholar
  114. 114.
    Ozen M, Kanra G, Kara A, et al. Long-term beneficial effects of dexamethasone on intellectual and neuropsychological outcome of children with pneumococcal meningitis. Scand J Infect Dis. 2006;38:104–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Scarborough M, Gordon SB, Whitty CJ, et al. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med. 2007;357:2441–50.PubMedCrossRefGoogle Scholar
  116. 116.
    Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267–84.PubMedCrossRefGoogle Scholar
  117. 117.
    Nguyen TH, Tran TH, Thwaites G, et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med. 2007;357:2431–40.PubMedCrossRefGoogle Scholar
  118. 118.
    Kamei S, Sekizawa T, Shiota H, et al. Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry. 2005;76:1544–9.PubMedCrossRefGoogle Scholar
  119. 119.
    Martinez-Torres F, Menon S, Pritsch M, et al. Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933]. BMC Neurol. 2008;8:40.Google Scholar
  120. 120.
    Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol. 2007;62:442–51.PubMedCrossRefGoogle Scholar
  121. 121.
    Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis with prominent leptomeningeal enhancement: a subset with a benign outcome. Arthritis Rheumatism. 2008;58:595–603.PubMedCrossRefGoogle Scholar
  122. 122.
    Salvarani C, Brown RD Jr, Calamia KT, et al. Angiography-negative primary central nervous system vasculitis: a syndrome involving small cerebral vessels. Medicine. 2008;87:264–71.PubMedCrossRefGoogle Scholar
  123. 123.
    Lanthier S, Lortie A, Michaud J, Laxer R, Jay V, deVeber G. Isolated angiitis of the CNS in children. Neurology. 2001;56:837–42.PubMedGoogle Scholar
  124. 124.
    Benseler SM, Silverman E, Aviv RI, et al. Primary central nervous system vasculitis in children. Arthritis Rheumatism. 2006;54:1291–7.PubMedCrossRefGoogle Scholar
  125. 125.
    Calabrese LH, Molloy ES, Singhal AB. Primary central nervous system vasculitis: progress and questions. Ann Neurol. 2007;62:430–2.PubMedCrossRefGoogle Scholar
  126. 126.
    Cupps TR, Moore PM, Fauci AS. Isolated angiitis of the central nervous system. Prospective diagnostic and therapeutic experience. Am J Med. 1983;74:97–105.PubMedCrossRefGoogle Scholar
  127. 127.
    Moore PM. Diagnosis and management of isolated angiitis of the central nervous system. Neurology. 1989;39:167–73.PubMedGoogle Scholar
  128. 128.
    Bitter KJ, Epstein LG, Melin-Aldana H, Curran JG, Miller ML. Cyclophosphamide treatment of primary angiitis of the central nervous system in children: report of 2 cases. J Rheumatol. 2006;33:2078–80.PubMedGoogle Scholar
  129. 129.
    Volcy M, Toro ME, Uribe CS, Toro G. Primary angiitis of the central nervous system: report of five biopsy-confirmed cases from Colombia. J Neurol Sci. 2004;227:85–9.PubMedCrossRefGoogle Scholar
  130. 130.
    Siva A. Vasculitis of the nervous system. J Neurol. 2001;248:451–68.PubMedCrossRefGoogle Scholar
  131. 131.
    Hajj-Ali RA, Ghamande S, Calabrese LH, Arroliga AC. Central nervous system vasculitis in the intensive care unit. Crit Care Clin. 2002;18:897–914.PubMedCrossRefGoogle Scholar
  132. 132.
    Moore PM, Richardson B. Neurology of the vasculitides and connective tissue diseases. J Neurol Neurosurg Psychiatry. 1998;65:10–22.PubMedCrossRefGoogle Scholar
  133. 133.
    Salvarani C, Brown RD Jr, Calamia KT, et al. Efficacy of tumor necrosis factor alpha blockade in primary central nervous system vasculitis resistant to immunosuppressive treatment. Arthritis Rheumatism. 2008;59:291–6.PubMedCrossRefGoogle Scholar
  134. 134.
    Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349:1543–54.PubMedCrossRefGoogle Scholar
  135. 135.
    Dalmau J, Tuzun E, Wu HY, et al. Paraneoplastic anti-N-methyl-d-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007;61:25–36.PubMedCrossRefGoogle Scholar
  136. 136.
    Vernino S, O’Neill BP, Marks RS, O’Fallon JR, Kimmel DW. Immunomodulatory treatment trial for paraneoplastic neurological disorders. Neuro-oncology. 2004;6:55–62.PubMedCrossRefGoogle Scholar
  137. 137.
    Uchuya M, Graus F, Vega F, Rene R, Delattre JY. Intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with antineuronal autoantibodies. J Neurol Neurosurg Psychiatry. 1996;60:388–92.PubMedCrossRefGoogle Scholar
  138. 138.
    Graus F, Vega F, Delattre JY, et al. Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies. Neurology. 1992;42:536–40.PubMedGoogle Scholar
  139. 139.
    Anderson NE, Rosenblum MK, Graus F, Wiley RG, Posner JB. Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology. 1988;38:1391–8.PubMedGoogle Scholar
  140. 140.
    Keime-Guibert F, Graus F, Fleury A, et al. Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone. J Neurol Neurosurg Psychiatry. 2000;68:479–82.PubMedCrossRefGoogle Scholar
  141. 141.
    David YB, Warner E, Levitan M, Sutton DM, Malkin MG, Dalmau JO. Autoimmune paraneoplastic cerebellar degeneration in ovarian carcinoma patients treated with plasmapheresis and immunoglobulin. A case report. Cancer. 1996;78:2153–6.PubMedCrossRefGoogle Scholar
  142. 142.
    Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. 2005;128:1764–77.PubMedCrossRefGoogle Scholar
  143. 143.
    Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7:1091–8.PubMedCrossRefGoogle Scholar
  144. 144.
    Vincent A, Buckley C, Schott JM, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain. 2004;127:701–12.PubMedCrossRefGoogle Scholar
  145. 145.
    Pozo-Rosich P, Clover L, Saiz A, Vincent A, Graus F. Voltage-gated potassium channel antibodies in limbic encephalitis. Ann Neurol. 2003;54:530–3.PubMedCrossRefGoogle Scholar
  146. 146.
    Thieben MJ, Lennon VA, Boeve BF, Aksamit AJ, Keegan M, Vernino S. Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody. Neurology. 2004;62:1177–82.PubMedGoogle Scholar
  147. 147.
    Buckley C, Oger J, Clover L, et al. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol. 2001;50:73–8.PubMedCrossRefGoogle Scholar
  148. 148.
    Kothbauer-Margreiter I, Sturzenegger M, Komor J, Baumgartner R, Hess CW. Encephalopathy associated with Hashimoto thyroiditis: diagnosis and treatment. J Neurol. 1996;243:585–93.PubMedCrossRefGoogle Scholar
  149. 149.
    Castillo P, Woodruff B, Caselli R, et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol. 2006;63:197–202.PubMedCrossRefGoogle Scholar
  150. 150.
    Josephs KA, Rubino FA, Dickson DW. Nonvasculitic autoimmune inflammatory meningoencephalitis. Neuropathology. 2004;24:149–52.PubMedCrossRefGoogle Scholar
  151. 151.
    Chong JY, Rowland LP. What’s in a NAIM? Hashimoto encephalopathy, steroid-responsive encephalopathy associated with autoimmune thyroiditis, or nonvasculitic autoimmune meningoencephalitis?[comment]. Arch Neurol. 2006;63:175–6.PubMedCrossRefGoogle Scholar
  152. 152.
    Mahad DJ, Staugaitis S, Ruggieri P, et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis and primary CNS demyelination. J Neurol Sci. 2005;228:3–5.PubMedCrossRefGoogle Scholar
  153. 153.
    Ferlazzo E, Raffaele M, Mazzu I, Pisani F. Recurrent status epilepticus as the main feature of Hashimoto’s encephalopathy. Epilepsy Behav. 2006;8:328–30.PubMedCrossRefGoogle Scholar
  154. 154.
    Vernino S, Geschwind M, Boeve B. Autoimmune encephalopathies. Neurologist. 2007;13:140–7.PubMedCrossRefGoogle Scholar
  155. 155.
    Chen HC, Marsharani U. Hashimoto’s encephalopathy. South Med J. 2000;93:504–6.PubMedGoogle Scholar
  156. 156.
    Caselli RJ, Boeve BF, Scheithauer BW, O’Duffy JD, Hunder GG. Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy. Neurology. 1999;53:1579–81.PubMedGoogle Scholar
  157. 157.
    Shaw PJ, Walls TJ, Newman PK, Cleland PG, Cartlidge NE. Hashimoto’s encephalopathy: a steroid-responsive disorder associated with high anti-thyroid antibody titers—report of 5 cases. Neurology. 1991;41:228–33.PubMedGoogle Scholar
  158. 158.
    Chong JY, Rowland LP, Utiger RD. Hashimoto encephalopathy: syndrome or myth? [see comment]. Arch Neurol. 2003;60:164–71.PubMedCrossRefGoogle Scholar
  159. 159.
    Mocellin R, Walterfang M, Velakoulis D. Hashimoto’s encephalopathy: epidemiology, pathogenesis and management. CNS Drugs. 2007;21:799–811.PubMedCrossRefGoogle Scholar
  160. 160.
    Jacob S, Rajabally YA. Hashimoto’s encephalopathy: steroid resistance and response to intravenous immunoglobulins. J Neurol Neurosurg Psychiatry. 2005;76:455–6.PubMedCrossRefGoogle Scholar
  161. 161.
    Wirkowski E, Libman RB, Batash M. Hashimot’s encephalopathy—response to intravenous immunoglobulin. J Stroke Cerebrovasc Dis. 1998;7:265–6.PubMedCrossRefGoogle Scholar
  162. 162.
    Boers PM, Colebatch JG. Hashimoto’s encephalopathy responding to plasmapheresis. J Neurol Neurosurg Psychiatry. 2001;70:132.PubMedCrossRefGoogle Scholar
  163. 163.
    Hussain NS, Rumbaugh J, Kerr D, Nath A, Hillis AE. Effects of prednisone and plasma exchange on cognitive impairment in Hashimoto encephalopathy. Neurology. 2005;64:165–6.PubMedCrossRefGoogle Scholar
  164. 164.
    Nagpal T, Pande S. Hashimoto’s encephalopathy: response to plasma exchange. Neurol India. 2004;52:245–7.PubMedGoogle Scholar
  165. 165.
    Palace J, Lang B. Epilepsy: an autoimmune disease? J Neurol Neurosurg Psychiatry. 2000;69:711–4.PubMedCrossRefGoogle Scholar
  166. 166.
    McKnight K, Jiang Y, Hart Y, et al. Serum antibodies in epilepsy and seizure-associated disorders. Neurology. 2005;65:1730–6.PubMedCrossRefGoogle Scholar
  167. 167.
    Verhelst H, Boon P, Buyse G, et al. Steroids in intractable childhood epilepsy: clinical experience and review of the literature. Seizure. 2005;14:412–21.PubMedGoogle Scholar
  168. 168.
    Sinclair DB. Prednisone therapy in pediatric epilepsy. Pediatr Neurol. 2003;28:194–8.PubMedGoogle Scholar
  169. 169.
    Okumura A, Tsuji T, Kato T, Natsume J, Negoro T, Watanabe K. ACTH therapy for generalized seizures other than spasms. Seizure. 2006;15:469–75.PubMedCrossRefGoogle Scholar
  170. 170.
    Prasad AN, Stafstrom CF, Holmes GL. Alternative epilepsy therapies: the ketogenic diet, immunoglobulins, and steroids. Epilepsia. 1996;37:S81–95.PubMedCrossRefGoogle Scholar
  171. 171.
    Bien CG, Granata T, Antozzi C, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain. 2005;128:454–71.PubMedCrossRefGoogle Scholar
  172. 172.
    Andrews PI, Dichter MA, Berkovic SF, Newton MR, McNamara JO. Plasmapheresis in Rasmussen’s encephalitis. Neurology. 1996;46:242–6.PubMedGoogle Scholar
  173. 173.
    Lousa M, Sanchez-Alonso S, Rodriguez-Diaz R, Dalmau J. Status epilepticus with neuron-reactive serum antibodies: response to plasma exchange. Neurology. 2000;54:2163–5.PubMedGoogle Scholar
  174. 174.
    Nahab F, Heller A, Laroche SM. Focal cortical resection for complex partial status epilepticus due to a paraneoplastic encephalitis. Neurologist. 2008;14:56–9.PubMedCrossRefGoogle Scholar
  175. 175.
    Mosca L, Appel LJ, Benjamin EJ, et al. Summary of the American Heart Association’s evidence-based guidelines for cardiovascular disease prevention in women. Arterioscl Thromb Vasc Biol. 2004;24:394–6.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Logan M. McDaneld
    • 1
  • Jeremy D. Fields
    • 1
    • 2
  • Dennis N. Bourdette
    • 1
  • Anish Bhardwaj
    • 1
    • 2
    • 3
    Email author
  1. 1.Departments of NeurologyOregon Health & Science UniversityPortlandUSA
  2. 2.Neurosciences Critical Care Program, Departments of Neurology, Neurological Surgery and Anesthesiology/Peri-Operative MedicineOregon Health & Science UniversityPortlandUSA
  3. 3.Department of Neurology, Tufts Medical CenterTufts University School of MedicineBostonUSA

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