Journal of Pediatric Epilepsy 2021; 10(01): 013-021
DOI: 10.1055/s-0040-1718723
Original Article

Electroencephalographic Findings in Pediatric Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis: The San Diego Experience

Aliya Frederick
1   Division of Child Neurology, University of California San Diego and Rady Children's Hospital, San Diego, California, United States
2   Department of Neurology, University of California San Diego, San Diego, California, United States
,
Jennifer H. Yang
1   Division of Child Neurology, University of California San Diego and Rady Children's Hospital, San Diego, California, United States
2   Department of Neurology, University of California San Diego, San Diego, California, United States
,
Natalie Guido-Estrada
1   Division of Child Neurology, University of California San Diego and Rady Children's Hospital, San Diego, California, United States
2   Department of Neurology, University of California San Diego, San Diego, California, United States
,
Jose Soria-Lopez
2   Department of Neurology, University of California San Diego, San Diego, California, United States
,
Shifteh Sattar
1   Division of Child Neurology, University of California San Diego and Rady Children's Hospital, San Diego, California, United States
2   Department of Neurology, University of California San Diego, San Diego, California, United States
› Author Affiliations
Funding None.

Abstract

Diagnosing anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis clinically can be challenging. There is a growing interest in identifying specific electroencephalographic features to help guide early management. A retrospective chart review was conducted of pediatric patients admitted to Rady Children's Hospital between January 1, 2010 and April 1, 2017. We included patients with the diagnosis of encephalitis who underwent continuous video electroencephalogram (VEEG) for at least 12 hours, and presented with less than 14 days of symptoms. We compared the electroencephalographic features of non-rapid eye movement (NREM) sleep between patients with antibody confirmed anti-NMDAR encephalitis and patients with encephalitis from other etiologies. We identified seven patients who met our inclusion criteria, five of whom were diagnosed with anti-NMDAR encephalitis. Four of the five patients had a significant reduction in NREM sleep, while one patient had increased NREM sleep associated with clinical catatonia and hypersomnolence. Sleep was preserved in the two cases of nonimmune mediated encephalitis. Our results suggest that a prolonged VEEG to capture sleep coupled with clinical features can aid in early diagnosis and treatment of anti-NMDAR encephalitis, often before confirmatory antibody testing is available.



Publication History

Received: 08 July 2020

Accepted: 10 September 2020

Article published online:
02 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Dalmau J, Bataller L. [Limbic encephalitis: the new cell membrane antigens and a proposal of clinical-immunological classification with therapeutic implications]. Neurologia 2007; 22 (08) 526-537
  • 2 Rosenfeld MR, Dalmau J. Anti-NMDA-receptor encephalitis and other synaptic autoimmune disorders. Curr Treat Options Neurol 2011; 13 (03) 324-332
  • 3 Florance NR, Davis RL, Lam C. et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66 (01) 11-18
  • 4 Florance-Ryan N, Dalmau J. Update on anti-N-methyl-D-aspartate receptor encephalitis in children and adolescents. Curr Opin Pediatr 2010; 22 (06) 739-744
  • 5 Brenton JN, Kim J, Schwartz RH, Schwartz RH. Approach to the management of pediatric-onset anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis: a case series. J Child Neurol 2016; 31 (09) 1150-1155
  • 6 Armangue T, Titulaer MJ, Málaga I. Spanish Anti-N-methyl-D-Aspartate Receptor (NMDAR) Encephalitis Work Group. et al. Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 2013; 162 (04) 850-856.e2
  • 7 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) 1091-1098
  • 8 Titulaer MJ, McCracken L, Gabilondo I. 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 (02) 157-165
  • 9 Nosadini M, Boniver C, Zuliani L. et al. Longitudinal electroencephalographic (EEG) findings in pediatric anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis: the Padua experience. J Child Neurol 2015; 30 (02) 238-245
  • 10 Sands TT, Nash K, Tong S, Sullivan J. Focal seizures in children with anti-NMDA receptor antibody encephalitis. Epilepsy Res 2015; 112: 31-36
  • 11 Sonderen AV, Arends S, Tavy DLJ. et al. Predictive value of electroencephalography in anti-NMDA receptor encephalitis. J Neurol Neurosurg Psychiatry 2018; 89 (10) 1101-1106
  • 12 Zhang Y, Liu G, Jiang MD, Li LP, Su YY. Analysis of electroencephalogram characteristics of anti-NMDA receptor encephalitis patients in China. Clin Neurophysiol 2017; 128 (07) 1227-1233
  • 13 Haberlandt E, Ensslen M, Gruber-Sedlmayr U. et al. Epileptic phenotypes, electroclinical features and clinical characteristics in 17 children with anti-NMDAR encephalitis. Eur J Paediatr Neurol 2017; 21 (03) 457-464
  • 14 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 (11) 1094-1100
  • 15 Jeannin-Mayer S, André-Obadia N, Rosenberg S. et al. EEG analysis in anti-NMDA receptor encephalitis: description of typical patterns. Clin Neurophysiol 2019; 130 (02) 289-296
  • 16 Kirkpatrick MP, Clarke CD, Sonmezturk HH, Abou-Khalil B. Rhythmic delta activity represents a form of nonconvulsive status epilepticus in anti-NMDA receptor antibody encephalitis. Epilepsy Behav 2011; 20 (02) 392-394
  • 17 Mohammad SS, Soe SM, Pillai SC. et al. Etiological associations and outcome predictors of acute electroencephalography in childhood encephalitis. Clin Neurophysiol 2016; 127 (10) 3217-3224
  • 18 da Silva-Júnior FP, Castro LH, Andrade JQ. et al. Serial and prolonged EEG monitoring in anti-N-Methyl-d-Aspartate receptor encephalitis. Clin Neurophysiol 2014; 125 (08) 1541-1544
  • 19 Gitiaux C, Simonnet H, Eisermann M. et al. Early electro-clinical features may contribute to diagnosis of the anti-NMDA receptor encephalitis in children. Clin Neurophysiol 2013; 124 (12) 2354-2361
  • 20 Baysal-Kirac L, Tuzun E, Altindag E. et al. Are there any specific EEG findings in autoimmune epilepsies?. Clin EEG Neurosci 2016; 47 (03) 224-234
  • 21 Freund B, Ritzl EK. A review of EEG in anti-NMDA receptor encephalitis. J Neuroimmunol 2019; 332: 64-68
  • 22 Gillinder L, Warren N, Hartel G, Dionisio S, O'Gorman C. EEG findings in NMDA encephalitis - A systematic review. Seizure 2019; 65: 20-24
  • 23 Ariño H, Muñoz-Lopetegi A, Martinez-Hernandez E. et al. Sleep disorders in anti-NMDAR encephalitis. Neurology 2020; 95 (06) e671-e684
  • 24 Kahn A, Dan B, Groswasser J, Franco P, Sottiaux M. Normal sleep architecture in infants and children. J Clin Neurophysiol 1996; 13 (03) 184-197
  • 25 Burgdorf JS, Vitaterna MH, Olker CJ. et al. NMDAR activation regulates the daily rhythms of sleep and mood. Sleep (Basel) 2019;42(10):
  • 26 Campbell IG, Gustafson LM, Feinberg I. The competitive NMDA receptor antagonist CPPene stimulates NREM sleep and eating in rats. Neuropsychopharmacology 2002; 26 (03) 348-357
  • 27 Kopp C, Longordo F, Nicholson JR, Lüthi A. Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function. J Neurosci 2006; 26 (48) 12456-12465
  • 28 Chen C, Hardy M, Zhang J, LaHoste GJ, Bazan NG. Altered NMDA receptor trafficking contributes to sleep deprivation-induced hippocampal synaptic and cognitive impairments. Biochem Biophys Res Commun 2006; 340 (02) 435-440
  • 29 Hughes EG, Peng X, Gleichman AJ. et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci 2010; 30 (17) 5866-5875
  • 30 Ang G, McKillop LE, Purple R. et al. Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice: relevance to neuropsychiatric disorders. Transl Psychiatry 2018; 8 (01) 154
  • 31 Yasuda K, Hayashi Y, Yoshida T. et al. Schizophrenia-like phenotypes in mice with NMDA receptor ablation in intralaminar thalamic nucleus cells and gene therapy-based reversal in adults. Transl Psychiatry 2017; 7 (02) e1047
  • 32 Nakazawa K, Jeevakumar V, Nakao K. Spatial and temporal boundaries of NMDA receptor hypofunction leading to schizophrenia. NPJ Schizophr 2017; 3: 7