Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU


Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient’s tendency toward autoimmunity. Antibodies directed toward neuronal cell surface antigens are directly pathogenic, whereas antibodies with intracellular targets may become pathogenic if the antigen is transiently exposed to the cell surface or via activation of cytotoxic T cells. Immune-mediated encephalitis is well recognized and may require intensive care due to status epilepticus, need for invasive ventilation, or dysautonomia. Patients with immune-mediated encephalitis may become critically ill and display clinically complex and challenging to treat movement disorders in over 80% of the cases (Zhang et al. in Neurocrit Care 29(2):264–272, 2018). Treatment options include immunotherapy and symptomatic agents affecting dopamine or acetylcholine neurotransmission. There has been no prior published guidance for management of these movement disorders for the intensivist. Herein, we discuss the immune-mediated encephalitis most likely to cause critical illness, clinical features and mechanisms of movement disorders and propose a management algorithm.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Dash D, Ihtisham K, Tripathi M, Tripathi M. Proportion and spectrum of movement disorders in adolescent and adult patients of autoimmune encephalitis of non-neoplastic aetiology. J Clin Neurosci. 2019;59:185–9.

    PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Cossu G, Colosimo C. Hyperkinetic movement disorder emergencies. Curr Neurol Neurosci Rep. 2017;17(1):6.

    PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Duan B-C, Weng W-C, Lin K-L, et al. Variations of movement disorders in anti-N-methyl-d-aspartate receptor encephalitis: a nationwide study in Taiwan. Medicine. 2016;95(37):e4365.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Baizabal-Carvallo JF, Stocco A, Muscal E, Jankovic J. The spectrum of movement disorders in children with anti-NMDA receptor encephalitis. Mov Disord. 2013;28(4):543–7.

    PubMed  Article  PubMed Central  Google Scholar 

  5. 5.

    Kleinig TJ, Thompson PD, Matar W, et al. The distinctive movement disorder of ovarian teratoma-associated encephalitis. Mov Disord. 2008;23(9):1256–61.

    PubMed  Article  PubMed Central  Google Scholar 

  6. 6.

    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(1):63–74.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Eskow Jaunarajs KL, Bonsi P, Chesselet MF, Standaert DG, Pisani A. Striatal cholinergic dysfunction as a unifying theme in the pathophysiology of dystonia. Prog Neurobiol. 2015;127–128:91–107.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  8. 8.

    Comella CL, Leurgans S, Wuu J, Stebbins GT, Chmura T. Dystonia Study Group. Rating scales for dystonia: a multicenter assessment. Mov Disord. 2003;18(3):303–12.

    PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Dale RC, Merheb V, Pillai S, et al. Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain. 2012;135(Pt 11):3453–68.

    PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Davies G, Irani SR, Coltart C, et al. Anti-N-methyl-d-aspartate receptor antibodies: a potentially treatable cause of encephalitis in the intensive care unit. Crit Care Med. 2010;38(2):679–82.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    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(12):1091–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Sutter R, Ristic A, Rüegg S, Fuhr P. Myoclonus in the critically ill: diagnosis, management, and clinical impact. Clin Neurophysiol. 2016;127(1):67–80.

    PubMed  Article  Google Scholar 

  13. 13.

    Balint B, Jarius S, Nagel S, et al. Progressive encephalomyelitis with rigidity and myoclonus: a new variant with DPPX antibodies. Neurology. 2014;82(17):1521–8.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Panzer JA, Anand R, Dalmau J, Lynch DR. Antibodies to dendritic neuronal surface antigens in opsoclonus myoclonus ataxia syndrome. J Neuroimmunol. 2015;15(286):86–92.

    Article  CAS  Google Scholar 

  15. 15.

    Caviness JN. Treatment of myoclonus. Neurotherapeutics. 2014;11(1):188–200.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Rogers JP, Pollak TA, Blackman G, David AS. Catatonia and the immune system: a review. Lancet Psychiatry. 2019;6(7):620–30.

    PubMed  Article  Google Scholar 

  17. 17.

    Herken J, Prüss H. Red flags: clinical signs for identifying autoimmune encephalitis in psychiatric patients. Front Psychiatry. 2017;16(8):25.

    Google Scholar 

  18. 18.

    Mikasova L, De Rossi P, Bouchet D, et al. Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis. Brain. 2012;135(Pt 5):1606–21.

    PubMed  Article  Google Scholar 

  19. 19.

    Dalmau J. NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: the 2016 Cotzias Lecture. Neurology. 2016;87(23):2471–82.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Varley JA, Webb AJS, Balint B, et al. The Movement disorder associated with NMDAR antibody-encephalitis is complex and characteristic: an expert video-rating study. J Neurol Neurosurg Psychiatry. 2019;90(6):724–6.

    PubMed  Article  Google Scholar 

  21. 21.

    van Sonderen A, Petit-Pedrol M, Dalmau J, Titulaer MJ. The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis. Nat Rev Neurol. 2017;13(5):290–301.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Lang B, Makuch M, Moloney T, et al. Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies. J Neurol Neurosurg Psychiatry. 2017;88(4):353–61.

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Binks SNM, Klein CJ, Waters P, Pittock SJ, Irani SR. LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes. J Neurol Neurosurg Psychiatry. 2018;89(5):526–34.

    PubMed  Article  Google Scholar 

  24. 24.

    Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol. 2011;69(5):892–900.

    PubMed  Article  Google Scholar 

  25. 25.

    O’Toole O, Lennon VA, Ahlskog JE, et al. Autoimmune chorea in adults. Neurology. 2013;80(12):1133–44.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  26. 26.

    Iyer RS, Ramakrishnan TCR, Karunakaran Shinto A, Kamaleshwaran KK. Faciobrachial dystonic seizures result from fronto-temporo-basalganglial network involvement. Epilepsy Behav Case Rep. 2017;8:47–50.

    PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Striano P. Faciobrachial dystonic attacks: seizures or movement disorder? Ann Neurol. 2011;70(1):179–80 author reply 180.

    PubMed  Article  Google Scholar 

  28. 28.

    Damato V, Balint B, Kienzler A-K, Irani SR. The clinical features, underlying immunology, and treatment of autoantibody-mediated movement disorders. Mov Disord. 2018;33(9):1376–89.

    PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

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

    PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Balint B, Vincent A, Meinck H-M, Irani SR, Bhatia KP. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. Brain. 2018;141(1):13–36.

    PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Balint B, Bhatia KP. Stiff person syndrome and other immune-mediated movement disorders—new insights. Curr Opin Neurol. 2016;29(4):496–506.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Werner C, Pauli M, Doose S, et al. Human autoantibodies to amphiphysin induce defective presynaptic vesicle dynamics and composition. Brain. 2016;139(Pt 2):365–79.

    PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Irani SR. “Moonlighting” surface antigens: a paradigm for autoantibody pathogenicity in neurology? Brain. 2016;139(Pt 2):304–6.

    PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Bien CG, Vincent A, Barnett MH, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain. 2012;135(Pt 5):1622–38.

    PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Cunningham MW, Cox CJ. Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond. Acta Physiol (Oxf). 2016;216(1):90–100.

    CAS  Article  Google Scholar 

  36. 36.

    Ben-Pazi H, Stoner JA, Cunningham MW. Dopamine receptor autoantibodies correlate with symptoms in Sydenham’s chorea. PLoS ONE. 2013;8(9):e73516.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    Church AJ, Dale RC, Giovannoni G. Anti-basal ganglia antibodies: a possible diagnostic utility in idiopathic movement disorders? Arch Dis Child. 2004;89(7):611–4.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Carecchio M, Cantello R, Comi C. Revisiting the molecular mechanism of neurological manifestations in antiphospholipid syndrome: beyond vascular damage. J Immunol Res. 2014;13(2014):239398.

    Google Scholar 

  39. 39.

    Zhang Y, Liu G, Jiang M, Chen W, He Y, Su Y. Clinical characteristics and prognosis of severe anti-N-methyl-d-aspartate receptor encephalitis patients. Neurocrit Care. 2018;29(2):264–72.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Harutyunyan G, Hauer L, Dünser MW, et al. Risk factors for intensive care unit admission in patients with autoimmune encephalitis. Front Immunol. 2017;28(8):835.

    Article  CAS  Google Scholar 

  41. 41.

    Cohen J, Sotoca J, Gandhi S, et al. Autoimmune encephalitis: a costly condition. Neurology. 2019;92(9):e964–e972.

    PubMed  Google Scholar 

  42. 42.

    Termsarasab P, Frucht SJ. Dystonic storm: a practical clinical and video review. J Clin Mov Disord. 2017;28(4):10.

    Article  Google Scholar 

  43. 43.

    McKeon A. The importance of early and sustained treatment of a common autoimmune encephalitis. Lancet Neurol. 2013;12(2):123–5.

    PubMed  Article  Google Scholar 

  44. 44.

    Thompson J, Bi M, Murchison AG, et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain. 2018;141(2):348–56.

    PubMed  Article  Google Scholar 

  45. 45.

    Barnes PJ. How corticosteroids control inflammation: quintiles Prize Lecture 2005. Br J Pharmacol. 2006;148(3):245–54.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Vandevyver S, Dejager L, Tuckermann J, Libert C. New insights into the anti-inflammatory mechanisms of glucocorticoids: an emerging role for glucocorticoid-receptor-mediated transactivation. Endocrinology. 2013;154(3):993–1007.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

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

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  48. 48.

    Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011;76(3):294–300.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Irani SR, Gelfand JM, Al-Diwani A, Vincent A. Cell-surface central nervous system autoantibodies: clinical relevance and emerging paradigms. Ann Neurol. 2014;76(2):168–84.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Scheibe F, Prüss H, Mengel AM, et al. Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology. 2017;88(4):366–70.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Lee W-J, Lee S-T, Moon J, et al. Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics. 2016;13(4):824–32.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Shin Y-W, Lee S-T, Park K-I, et al. Treatment strategies for autoimmune encephalitis. Ther Adv Neurol Disord. 2018;11:1756285617722347.

    PubMed  Google Scholar 

  53. 53.

    Frucht SJ. Treatment of movement disorder emergencies. Neurotherapeutics. 2014;11(1):208–12.

    PubMed  Article  Google Scholar 

  54. 54.

    Robottom BJ, Weiner WJ, Factor SA. Movement disorders emergencies. Part 1: Hypokinetic disorders. Arch Neurol. 2011;68(5):567–72.

    PubMed  Article  Google Scholar 

  55. 55.

    Robottom BJ, Factor SA, Weiner WJ. Movement disorders emergencies. Part 2: hyperkinetic disorders. Arch Neurol. 2011;68(6):719–24.

    PubMed  Article  Google Scholar 

  56. 56.

    Schaefer SM, Rostami R, Greer DM. Movement disorders in the intensive care unit. Semin Neurol. 2016;36(6):607–14.

    PubMed  Article  Google Scholar 

  57. 57.

    Hughes JD, Rabinstein AA. Early diagnosis of paroxysmal sympathetic hyperactivity in the ICU. Neurocrit Care. 2014;20(3):454–9.

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Relja M, Miletić V. When movement disorders hurt: addressing pain in hyperkinetic disorders. Parkinsonism Relat Disord. 2017;44:110–3.

    PubMed  Article  Google Scholar 

  59. 59.

    Gadoth A, Pittock SJ, Dubey D, et al. Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol. 2017;82(1):79–92.

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Mittal MK, Rabinstein AA, Hocker SE, Pittock SJ, Wijdicks EFM, McKeon A. Autoimmune encephalitis in the ICU: analysis of phenotypes, serologic findings, and outcomes. Neurocrit Care. 2016;24(2):240–50.

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Liu H, Jian M, Liang F, Yue H, Han R. Anti-N-methyl-d-aspartate receptor encephalitis associated with an ovarian teratoma: two cases report and anesthesia considerations. BMC Anesthesiol. 2015;16(15):150.

    Article  CAS  Google Scholar 

  62. 62.

    Solt K, Eger EI, Raines DE. Differential modulation of human N-methyl-d-aspartate receptors by structurally diverse general anesthetics. Anesth Analg. 2006;102(5):1407–11.

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Hollman JH, Brey RH, Bang TJ, Kaufman KR. Does walking in a virtual environment induce unstable gait? An examination of vertical ground reaction forces. Gait Posture. 2007;26(2):289–94.

    PubMed  Article  Google Scholar 

  64. 64.

    Sonner JM, Zhang Y, Stabernack C, Abaigar W, Xing Y, Laster MJ. GABA(A) receptor blockade antagonizes the immobilizing action of propofol but not ketamine or isoflurane in a dose-related manner. Anesth Analg. 2003;96(3):706–12 table of contents.

    CAS  PubMed  Google Scholar 

  65. 65.

    Kingston S, Mao L, Yang L, Arora A, Fibuch EE, Wang JQ. Propofol inhibits phosphorylation of N-methyl-d-aspartate receptor NR1 subunits in neurons. Anesthesiology. 2006;104(4):763–9.

    CAS  PubMed  Article  Google Scholar 

  66. 66.

    Kozinn J, Mao L, Arora A, Yang L, Fibuch EE, Wang JQ. Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol. Anesthesiology. 2006;105(6):1182–91.

    PubMed  Article  Google Scholar 

  67. 67.

    Lapébie F-X, Kennel C, Magy L, et al. Potential side effect of propofol and sevoflurane for anesthesia of anti-NMDA-R encephalitis. BMC Anesthesiol. 2014;16(14):5.

    Article  Google Scholar 

  68. 68.

    Hemphill S, McMenamin L, Bellamy MC, Hopkins PM. Propofol infusion syndrome: a structured literature review and analysis of published case reports. Br J Anaesth. 2019;122(4):448–59.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    Gommers D, Bakker J. Medications for analgesia and sedation in the intensive care unit: an overview. Crit Care. 2008;12(Suppl 3):S4.

    PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet. 2017;56(8):893–913.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. 71.

    Gittis AH, Leventhal DK, Fensterheim BA, Pettibone JR, Berke JD, Kreitzer AC. Selective inhibition of striatal fast-spiking interneurons causes dyskinesias. J Neurosci. 2011;31(44):15727–31.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. 72.

    Seifi A, Kitchen DL. Management of dyskinesia in anti-NMDAR encephalitis with tramadol. Clin Neurol Neurosurg. 2016;147:105–7.

    PubMed  Article  PubMed Central  Google Scholar 

  73. 73.

    Potschka H, Friderichs E, Löscher W. Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy. Br J Pharmacol. 2000;131(2):203–12.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  74. 74.

    Mohammad SS, Jones H, Hong M, et al. Symptomatic treatment of children with anti-NMDAR encephalitis. Dev Med Child Neurol. 2016;58(4):376–84.

    PubMed  Article  PubMed Central  Google Scholar 

  75. 75.

    Jankovic J. Dopamine depleters in the treatment of hyperkinetic movement disorders. Expert Opin Pharmacother. 2016;17(18):2461–70.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  76. 76.

    Chen JJ, Ondo WG, Dashtipour K, Swope DM. Tetrabenazine for the treatment of hyperkinetic movement disorders: a review of the literature. Clin Ther. 2012;34(7):1487–504.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  77. 77.

    Peckham AM, Nicewonder JA. VMAT2 inhibitors for tardive dyskinesia-practice implications. J Pharm Pract. 2018;1:897190018756512.

    Google Scholar 

  78. 78.

    Seeberger LC, Hauser RA. Valbenazine for the treatment of tardive dyskinesia. Expert Opin Pharmacother. 2017;18(12):1279–87.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  79. 79.

    Jankovic J. An update on new and unique uses of botulinum toxin in movement disorders. Toxicon. 2018;1(147):84–8.

    Article  CAS  Google Scholar 

  80. 80.

    Hallett M. Mechanism of action of botulinum neurotoxin: unexpected consequences. Toxicon. 2018;1(147):73–6.

    Article  CAS  Google Scholar 

  81. 81.

    Puschmann A, Wszolek ZK. Diagnosis and treatment of common forms of tremor. Semin Neurol. 2011;31(1):65–77.

    PubMed  PubMed Central  Article  Google Scholar 

  82. 82.

    Mohammad SS, Dale RC. Principles and approaches to the treatment of immune-mediated movement disorders. Eur J Paediatr Neurol. 2018;22(2):292–300.

    PubMed  Article  Google Scholar 

  83. 83.

    Jankovic J. Treatment of hyperkinetic movement disorders. Lancet Neurol. 2009;8(9):844–56.

    CAS  PubMed  Article  Google Scholar 

Download references


No financial support was used in this project.

Author information




FA and EFW involved in: (1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it critically for important intellectual content; (3) final approval of the version to be published.

Corresponding author

Correspondence to Farwa Ali.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical Approval

IRB approval was not required for this review article and no patient protected health information was accessed.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (MP4 4643 kb)

Supplementary material 2 (PDF 111 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ali, F., Wijdicks, E.F. Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU. Neurocrit Care 32, 286–294 (2020).

Download citation


  • Autoimmune
  • Encephalitis
  • Movement disorder
  • Dyskinesia
  • Chorea