J Neurocrit Care.  2017 Dec;10(2):60-68. 10.18700/jnc.170029.

Corticosteroid Treatment in Autoimmune Encephalitis

• Sunwoo JS

• KMID: 2405759
• DOI: http://doi.org/10.18700/jnc.170029

Abstract

An increasing number of neuronal autoantibodies which target cell surface or synaptic proteins have been discovered over the last decade. Autoimmune encephalitis refers to this new category of autoimmune-mediated neurological disorders, which involve the central nervous system. Recent studies have established that autoimmune encephalitis is now the major cause of encephalitis, which was previously considered to be encephalitis of an unknown etiology. Moreover, the fact that autoimmune encephalitis is potentially treatable with immunomodulating therapy has changed the paradigm for the diagnosis and treatment of acute encephalitis syndrome. We herein review the pathophysiology, clinical manifestations, diagnosis, and treatment of autoimmune encephalitis with a focus on corticosteroid therapy as the first-line immunotherapy. In addition, regarding the diagnostic approach, we emphasize the differentiation between autoimmune and infectious encephalitis, because this distinction is not necessarily clear-cut in real clinical practice and should be considered when determining the initiation and type of immunotherapy.

Keyword

Autoimmune diseases of the nervous system; Immunotherapy; Glucocorticoids; Autoantibodies

MeSH Terms

Autoantibodies
Autoimmune Diseases of the Nervous System
Central Nervous System
Diagnosis
Encephalitis*
Glucocorticoids
Immunotherapy
Infectious Encephalitis
Nervous System Diseases
Neurons
Autoantibodies
Glucocorticoids

Reference

1. Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013; 57:1114–28.

2. Vora NM, Holman RC, Mehal JM, Steiner CA, Blanton J, Sejvar J. Burden of encephalitis-associated hospitalizations in the United States, 1998-2010. Neurology. 2014; 82:443–51.

3. Glaser CA, Honarmand S, Anderson LJ, Schnurr DP, Forghani B, Cossen CK, et al. Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis. 2006; 43:1565–77.

4. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016; 15:391–404.

5. Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010; 10:835–44.

6. Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis. 2012; 54:899–904.

7. Sillevis Smitt PA, Manley GT, Posner JB. Immunization with the paraneoplastic encephalomyelitis antigen HuD does not cause neurologic disease in mice. Neurology. 1995; 45:1873–8.

8. Lancaster E, Dalmau J. Neuronal autoantigens--pathogenesis, associated disorders and antibody testing. Nat Rev Neurol. 2012; 8:380–90.

9. Kazarian M, Calbo J, Proost N, Carpenter CL, Berns A, Laird-Offringa IA. Immune response in lung cancer mouse model mimics human anti-Hu reactivity. J Neuroimmunol. 2009; 217:38–45.

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

11. Leypoldt F, Armangue T, Dalmau J. Autoimmune encephalopathies. Ann N Y Acad Sci. 2015; 1338:94–114.

12. Sunwoo JS, Lee ST, Byun JI, Moon J, Shin JW, Jeong DE, et al. Clinical manifestations of patients with CASPR2 antibodies. J Neuroimmunol. 2015; 281:17–22.

13. 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; 7:1091–8.

14. Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010; 30:5866–75.

15. Lancaster E, Lai M, Peng X, Hughes E, Constantinescu R, Raizer J, et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol. 2010; 9:67–76.

16. Lai M, Huijbers MG, Lancaster E, Graus F, Bataller L, Balice-Gordon R, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol. 2010; 9:776–85.

17. Sili U, Kaya A, Mert A; HSV Encephalitis Study Group. Herpes simplex virus encephalitis: clinical manifestations, diagnosis and outcome in 106 adult patients. J Clin Virol. 2014; 60:112–8.

18. Scheid R, Voltz R, Vetter T, Sabri O, von Cramon DY. Neurosyphilis and paraneoplastic limbic encephalitis: important differential diagnoses. J Neurol. 2005; 252:1129–32.

19. Byun JI, Lee ST, Jung KH, Sunwoo JS, Moon J, Kim TJ, et al. Prevalence of antineuronal antibodies in patients with encephalopathy of unknown etiology: data from a nationwide registry in Korea. J Neuroimmunol. 2016; 293:34–8.

20. Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011; 10:63–74.

21. Sunwoo JS, Jung DC, Choi JY, Kang UG, Lee ST, Lee SK, et al. Successful treatment of refractory dyskinesia secondary to anti-N-methyl-D-aspartate receptor encephalitis with electroconvulsive therapy. J ECT. 2016; 32:e13–4.

22. Sansing LH, Tüzün E, Ko MW, Baccon J, Lynch DR, Dalmau J. A patient with encephalitis associated with NMDA receptor antibodies. Nat Clin Pract Neurol. 2007; 3:291–6.

23. Byun JI, Lee ST, Moon J, Jung KH, Shin JW, Sunwoo JS, et al. Cardiac sympathetic dysfunction in anti-NMDA receptor encephalitis. Auton Neurosci. 2015; 193:142–6.

24. Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology. 2012; 79:1094–100.

25. Irani SR, Gelfand JM, Al-Diwani A, Vincent A. Cell-surface central nervous system autoantibodies: clinical relevance and emerging paradigms. Ann Neurol. 2014; 76:168–84.

26. Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology. 2011; 77:179–89.

27. Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014; 13:167–77.

28. Lee SK, Lee ST. The laboratory diagnosis of autoimmune encephalitis. J Epilepsy Res. 2016; 6:45–52.

29. Lee WJ, Lee ST, Byun JI, Sunwoo JS, Kim TJ, Lim JA, et al. Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology. 2016; 86:1683–91.

30. Dalmau J, Furneaux HM, Gralla RJ, Kris MG, Posner JB. Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer--a quantitative western blot analysis. Ann Neurol. 1990; 27:544–52.

31. Saylor D, Thakur K, Venkatesan A. Acute encephalitis in the immunocompromised individual. Curr Opin Infect Dis. 2015; 28:330–6.

32. Pruitt AA. Nervous system viral infections in immunocompromised hosts. Handb Clin Neurol. 2014; 123:685–704.

33. Gable MS, Gavali S, Radner A, Tilley DH, Lee B, Dyner L, et al. Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis. 2009; 28:1421–9.

34. Armangue T, Leypoldt F, Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol. 2014; 27:361–8.

35. Elbers JM, Bitnun A, Richardson SE, Ford-Jones EL, Tellier R, Wald RM, et al. A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease? Pediatrics. 2007; 119:e399–407.

36. Sunwoo JS, Lee ST, Jung KH, Park KI, Moon J, Jung KY, et al. Clinical characteristics of severe Japanese encephalitis: a case series from South Korea. Am J Trop Med Hyg. 2017; 97:369–75.

37. Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, Sangha N, Martinez-Lage M, Dalmau J. Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology. 2011; 77:589–93.

38. Sunwoo JS, Chu K, Byun JI, Moon J, Lim JA, Kim TJ, et al. Intrathecal-specific glutamic acid decarboxylase antibodies at low titers in autoimmune neurological disorders. J Neuroimmunol. 2016; 290:15–21.

39. Rubenstein JL, Combs D, Rosenberg J, Levy A, McDermott M, Damon L, et al. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood. 2003; 101:466–8.

40. McKeon A. Paraneoplastic and other autoimmune disorders of the central nervous system. Neurohospitalist. 2013; 3:53–64.

41. Lee WJ, Lee ST, Moon J, Sunwoo JS, Byun JI, Lim JA, et al. Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics. 2016; 13:824–32.

42. Lim JA, Lee ST, Moon J, Jun JS, Park BS, Byun JI, et al. New feasible treatment for refractory autoimmune encephalitis: low-dose interleukin-2. J Neuroimmunol. 2016; 299:107–11.

43. Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013; 12:157–65.

44. Clowse ME, Behera MA, Anders CK, Copland S, Coffman CJ, Leppert PC, et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health (Larchmt). 2009; 18:311–9.

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

46. Barnes PJ. How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol. 2006; 148:245–54.

47. Witt KA, Sandoval KE. Steroids and the blood-brain barrier: therapeutic implications. Adv Pharmacol. 2014; 71:361–90.

48. Slade JD, Hepburn B. Prednisone-induced alterations of circulating human lymphocyte subsets. J Lab Clin Med. 1983; 101:479–87.

49. Lahood N, Emerson SS, Kumar P, Sorensen RU. Antibody levels and response to pneumococcal vaccine in steroiddependent asthma. Ann Allergy. 1993; 70:289–94.

50. Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006; 81:1361–7.

51. Shin YW, Lee ST, Shin JW, Moon J, Lim JA, Byun JI, et al. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol. 2013; 265:75–81.

52. Irani SR, Stagg CJ, Schott JM, Rosenthal CR, Schneider SA, Pettingill P, et al. Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain. 2013; 136(Pt 10):3151–62.

53. van Sonderen A, Ariño H, Petit-Pedrol M, Leypoldt F, Körtvélyessy P, Wandinger KP, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology. 2016; 87:521–8.

54. Carvajal-González A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain. 2014; 137(Pt 8):2178–92.