Rare: could represent 4 % of the cases of encephalitis admitted to intensive care. Paraneoplastic (generally) syndrome presenting with neuropsychiatric disorders of sudden onset. It occurs most often in girls or young women, and is often associated with a benign ovarian tumor (teratoma). It seems that the presence of nervous tissue and therefore of NMDA receptors in the tumor is the source of antigen that generates these autoantibodies. In prepubertal chidren, the syndrome is as frequent in boys as in girls and is not associated with the presence of a tumor. The presence of antibodies leads to a decreased density of the surface NMDA receptors at the postsynaptic site: the associated inactivation of the GABA-ergic interneurones causes a hyperglutaminergic state explaining the neurologic symptomatology.

Diagnosis: presence of antibodies anti-NMDA in blood and CSF. These autoantibodies are directed against subunit 1 of NMDA receptors which are mainly located at the level of the hippocampus and brain stem.

Signs: increasingly important confusion, personality changes, memory disorders, agitation, paranoid thoughts, stereotyped movements (86 %), seizures (77 %), instability of the autonomic system (86 %) with fever of central origin, heart rhythm disorders (the implantation of a pacemaker is occasionally necessary) or central hypoventilation (23 %).

Treatment: surgical resection of the tumor is curative in a few weeks if the interval of time between the onset of symptoms and surgery is short. In cases where no tumor is discovered or the response to surgery is partial, treatment include immunotherapy by IV immunoglobulin, corticosteroids and plasmapheresis, or even rituximab or cyclophophamide.

Anesthetic implications: 

ECG monitoring; management of psychiatric and dysautonomic disorders: be prepared to use an antihypertensive and or β-blocker;  risk of seizures.

Avoid 

-        ketamine (it is acting on the voltage-gated calcium channel coupled to the NMDA receptor), methadone, and N2O as they interact with the NMDA receptor

-        high concentrations of halogenated agents (> 1 MAC)

-        propofol at high doses that can block the NMDA receptors

-        xenon

-        acidosis as it inhibits the glutaminergic and glycinergic sites of the NMDA receptors

Possible choices: etomidate, alpha-2 agonists, benzodiazepines, opioids and muscle relaxants.

The main metabolite of tramadol could decrease dyskinesia, as it inhibits non-competitively the NMDA receptors and so, lessens the synaptic expression of the GluN2B subunit of the NMDA receptor.

Monitoring of the depth of anesthesia (BIS and others) is not always easy; monitoring of ventilation in the post-anesthesia period.

References : 

-         Lesher AP, Myers TJ, Tecklenburg F, Streck C. 
Anti-N-methyl-D-aspartate receptor encephalitis associated with an ovarian teratoma in an adolescent female. 
J Pediatr Surg 2010; 45: 1550-3

-        Lamarque M, Psimaras D, Ducray F et al. 
Encéphalite autoimmune à anticorps anti-récepteur NMDA, une cause fréquente d’encéphalite en réanimation. 
Réanimation 2011 ; 30 : 397-407.

-         Millichap JJ, Goldstein JL, Laux LC, Nordli DR, Stack CV, Wainwright MS. 
Ictal asystole and anti-N-methyl-D-aspartate receptor antibody encephalitis. 
Pediatrics 2014; 133: e 781-6.

-        Splinter WM, Eipe N. 
Anti-NMDA receptor antibodies encephalitis. 
Pediatr Anesth 2009 ; 19 : 911-3

-         Pryzbylkowski PG, Dunkman WJ, Liu R, Chen L. 
Anti-N-methyl-D-aspartate receptor encephalitis and its anesthetic implications. 
Anesth Analg 2011 ; 113 : 1188-91.

-         Liu H, Jian M, Liang F, Yue H, Han R. 
Anti-N-methyl-D-aspartate receptor encephalitis associated with an ovarian teratoma: two case reports and anesthesia considerations. 
BMC Anesthesiology 2015; 15: 150; DOI 10.1186/s12871-015-0134-5

-        Senbruna B, Lerman J.
Anesthesia management for a boy with anti-N-methyl-D-aspartate receptor encephalitis.
A & A Case Reports 2015; 5: 182-4.

-        Ho KM.
Use of tramadol to attenuate severe dyskinesia in anti-N-methyl-D-aspartate receptor encephalitis.
Anaesth Intens Care 2019 ; 47 :561-2.

-        Bell M, Friedman M, Matar M, et al.
Anesthesia for pediatric patients with anti-NMDA receptor encephalitis: A retrospective case series.
Pediatr Anesth 2021; 31:316–22.

-        Lapébie F-X, Kenel C, Magy L, Projetti F, Honnorat J, Pichon N, Vignon P, François B. 
Potential side effects of propofol and sevoflurane for anesthesia of anti-NMDA-R encephalitis.
BMC Anesthesiology 2014 ; 14 : 5

-        Ming-Sung YEH, Guan-Yu CHEN, Chia-Heng LIN, Chia-Yu LIN
A combination of midazolam and dexmedetomidine for anesthesia management in a patient with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis : a case report.
J Clin Anesth 2021 ; 75 : 110509

Updated: October 2021