Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis

Grace Gombolay¹, J Nicholas Brenton², Jennifer H Yang³, Coral M Stredny⁴, Ryan Kammeyer⁵, Kristen S Fisher⁶, Alexander J Sandweiss⁶, Timothy A Erickson⁷, Varun Kannan⁸, Catherine Otten⁹, Claude Steriade¹⁰, NgocHanh Vu¹¹, Jonathan D Santoro¹², Karla Robles-Lopez¹³, Robert Goodrich¹⁴, Scott Otallah¹⁴, Janetta Arellano¹⁵, Andrew Christiana¹⁰, Morgan Morris¹⁶, Mark P Gorman⁴, Alexandra B Kornbluh¹⁷, Ilana Kahn¹⁷, Leigh Sepeta¹⁷, Yike Jiang¹⁸, Eyal Muscal¹⁹, Kristy O Murray²⁰, Manikum Moodley¹³, Duriel Hardy¹³

Affiliations

¹ Department of Pediatrics, Emory University SOM and Children's Healthcare of Atlanta, Atlanta, Georgia. Electronic address: ggombol@emory.edu.
² Division of Pediatric Neurology, Department of Neurology, University of Virginia Health System, Charlottesville, Virginia.
³ Department of Pediatrics, University of California San Diego and Rady Children's Hospital San Diego, San Diego, California.
⁴ Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
⁵ Department of Pediatrics, University of Colorado SOM and Children's Hospital Colorado, Denver, Colorado.
⁶ Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
⁷ Section of Pediatric Tropical Medicine, Department of Pediatrics, Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas; Laboratories for Emerging and Tropical Diseases, School of Public Health, Texas A&M University, College Station, Texas.
⁸ Department of Pediatrics, Emory University SOM and Children's Healthcare of Atlanta, Atlanta, Georgia; Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
⁹ Department of Pediatrics, Seattle Children's/University of Washington, Seattle, Washington.
¹⁰ Department of Neurology, New York University SOM, New York, New York.
¹¹ Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee.
¹² Department of Neurology and Pediatrics, Children's Hospital Los Angeles; Keck School of Medicine, University of Southern California, Los Angeles, California.
¹³ Department of Pediatrics, University of Texas at Austin and Dell Medical School, Austin, Texas.
¹⁴ Department of Neurology, Atrium Wake Forest Baptist Health, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
¹⁵ Pediatric Neurology, Children's Hospital of Orange County, Orange, California.
¹⁶ Department of Pediatrics, Emory University SOM and Children's Healthcare of Atlanta, Atlanta, Georgia.
¹⁷ Department of Pediatrics, Children's National Hospital, George Washington University Medical School, Washington, District of Columbia.
¹⁸ Section of Rheumatology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
¹⁹ Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas; Section of Rheumatology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
²⁰ Section of Pediatric Tropical Medicine, Department of Pediatrics, Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

PMID: 39094249
PMCID: PMC11381152
DOI: 10.1016/j.pediatrneurol.2024.07.009

Multicenter Study

Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis

Grace Gombolay et al. Pediatr Neurol. 2024 Oct.

. 2024 Oct:159:12-15.

doi: 10.1016/j.pediatrneurol.2024.07.009. Epub 2024 Jul 17.

Authors

Affiliations

¹ Department of Pediatrics, Emory University SOM and Children's Healthcare of Atlanta, Atlanta, Georgia. Electronic address: ggombol@emory.edu.
² Division of Pediatric Neurology, Department of Neurology, University of Virginia Health System, Charlottesville, Virginia.
³ Department of Pediatrics, University of California San Diego and Rady Children's Hospital San Diego, San Diego, California.
⁴ Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
⁵ Department of Pediatrics, University of Colorado SOM and Children's Hospital Colorado, Denver, Colorado.
⁶ Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
⁷ Section of Pediatric Tropical Medicine, Department of Pediatrics, Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas; Laboratories for Emerging and Tropical Diseases, School of Public Health, Texas A&M University, College Station, Texas.
⁸ Department of Pediatrics, Emory University SOM and Children's Healthcare of Atlanta, Atlanta, Georgia; Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
⁹ Department of Pediatrics, Seattle Children's/University of Washington, Seattle, Washington.
¹⁰ Department of Neurology, New York University SOM, New York, New York.
¹¹ Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee.
¹² Department of Neurology and Pediatrics, Children's Hospital Los Angeles; Keck School of Medicine, University of Southern California, Los Angeles, California.
¹³ Department of Pediatrics, University of Texas at Austin and Dell Medical School, Austin, Texas.
¹⁴ Department of Neurology, Atrium Wake Forest Baptist Health, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
¹⁵ Pediatric Neurology, Children's Hospital of Orange County, Orange, California.
¹⁶ Department of Pediatrics, Emory University SOM and Children's Healthcare of Atlanta, Atlanta, Georgia.
¹⁷ Department of Pediatrics, Children's National Hospital, George Washington University Medical School, Washington, District of Columbia.
¹⁸ Section of Rheumatology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
¹⁹ Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas; Section of Rheumatology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
²⁰ Section of Pediatric Tropical Medicine, Department of Pediatrics, Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

PMID: 39094249
PMCID: PMC11381152
DOI: 10.1016/j.pediatrneurol.2024.07.009

Abstract

Background: Isolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE.

Methods: This multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data was performed.

Results: Of 249 children included, 12 (5%) had only psychiatric symptoms without other typical clinical features of autoimmune encephalitis at presentation. All but one (11 of 12 = 92%) had at least one abnormal finding on initial ancillary testing: eight of 12 (67%) had an abnormal EEG, six of 12 (50%) had an abnormal MRI, and five of 12 (42%) demonstrated CSF pleocytosis. The single patient with a normal MRI, EEG, and CSF profile had low positive CSF NMDA antibody (titer of 1:1), and symptoms improved without immunotherapy.

Conclusions: Isolated first-episode psychiatric symptoms in pNMDARE are uncommon, and the majority of children will exhibit additional neurodiagnostic abnormalities. Delaying immunotherapy in a child with isolated psychiatric symptoms and normal neurodiagnostic testing may be warranted while awaiting confirmatory antibody testing.

Keywords: Anti-NMDA receptor encephalitis; Anti-NMDAR encephalitis; Anti-NMDARE; Autoimmune encephalitis; Encephalitis; Pediatric autoimmune encephalitis.

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Conflict of interest statement

Declaration of competing interest Dr. Gombolay receives an honorarium as a Media Editor for Pediatric Neurology. Dr. Brenton has received compensation for consulting for I-ACT for Children on a Novartis-sponsored project and Cycle Pharmaceuticals. Dr. Mark Gorman has been personally compensated for work on a medical advisory board for Arialys Therapeutics. Dr. Santoro receives consultation fees from Biogen, UCB, and Cycle Pharma on conditions unrelated to the data presented. The rest of the authors have no relevant conflicts of interest to report.

Figures

**Figure 1:**
Flow diagram of the pediatric anti-NMDA receptor encephalitis participants included and excluded from this study.

See this image and copyright information in PMC

References

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Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis

Affiliations

Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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MeSH terms

Grants and funding

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Full Text Sources