Initial MRI, EEG, and CSF White Cell Count Are Abnormal in Children with Anti-NMDA Receptor Encephalitis with Isolated Psychiatric Symptoms
Grace Gombolay1, James Brenton2, Jonathan Santoro3, Coral Stredny4, Ryan Kammeyer5, Kristen Fisher6, Alexander Sandweiss6, Tim Erickson6, Varun Kannan1, Catherine Otten7, NgocHanh Vu8, Jennifer Yang9, Karla Robles Lopez10, Robert Goodrich11, Scott Otallah11, Janetta Arellano12, Andrew Christiana13, Claude Steriade13, Morgan Morris1, Alexandra Kornbluh14, Ilana Kahn14, Leigh Sepeta14, Yike Jiang6, Eyal Muscal6, Kristy Murray6, Manikum Moodley10, Duriel Hardy10, Mark Gorman4
1Emory University/Children'S Healthcare of Atlanta, 2University of Virginia Health System, 3Department of Neurology, Children's Hospital Los Angeles, 4Children's Hospital Boston, 5Childrens Hospital Colorado, 6Baylor College of Medicine, 7Seattle Children's, 8Vanderbilt University, Child Neurology, 9Rady Childrens Hospital/UCSD, 10UNIVERSITY OF TEXAS AT AUSTIN/DMS, 11Wake Forest Baptist Medical Center, 12UCI CHOC, 13NYU, 14Children's National Hospital
Objective:
To assess whether initial ancillary tests (brain magnetic resonance imaging-MRI, electroencephalogram-EEG, and/or cerebrospinal fluid-CSF white blood cell count) are abnormal in children with isolated psychiatric symptoms and anti-NMDA receptor encephalitis.
Background:
Isolated psychiatric symptoms can be the initial symptom of pediatric anti-NMDA receptor autoimmune encephalitis (pNMDARE). However, the utility of initiating empiric immunotherapy prior to autoantibody test results is poorly understood. Identification of appropriate patients reduces risk of administering unnecessary treatment. Here we assess the characteristics of isolated new onset psychiatric symptoms in pNMDARE.
Design/Methods:
This multi-center retrospective cohort study from CONNECT (CONquering Neuroinflammation and Epilepsies ConsorTium) from 14 institutions included children under 18 years old who were diagnosed with pNMDARE from January 1, 2008 – September 1, 2022. Psychiatric symptoms were defined as the presence of catatonia, agitation, hallucinations, confusion, behavioral changes, anxiety, and suicidal ideation. Patients who had non-psychiatric symptoms (seizures, movement disorders, autonomic instability, speech changes, and hypoventilation) were excluded. Descriptive statistics using means and medians and comparisons for continuous versus discrete data were performed.
Results:
Out of 249 children included, twelve (5%) had only psychiatric symptoms without other typical clinical features of autoimmune encephalitis at presentation. All but one (11/12=92%) had at least one abnormal finding on initial ancillary testing: 8/12 (67%) had an abnormal EEG, 6/12 (50%) had an abnormal MRI, and 5/12 (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 is uncommon, and the majority of children will exhibit additional abnormalities on diagnostic testing (EEG, MRI, and/or CSF). Thus, it is reasonable to await diagnostic confirmation with antibody testing prior to starting immunotherapy in a patient with isolated psychiatric symptoms, especially without abnormal ancillary testing.