(From the March 2016 issue of Research Now)
Autoimmune encephalitis is a newly characterized condition with symptoms that may include alteration of mental status, behavioral changes, seizures and abnormal involuntary movements. Evaluating and treating neuroimmunological disorders – autoimmune conditions that impact the nervous system – can be challenging. Although criteria for diagnosing and testing exist for some of these disorders, autoimmune encephalitis is currently a clinical diagnosis without widely accepted diagnostic criteria.
An interdisciplinary team of clinician researchers from Nationwide Children’s Hospital recently published a study in the journal Pediatric Neurology examining the results of two common tests – magnetic resonance imaging (MRI) and electroencephalography (EEG) – and identifying common patterns that support the diagnosis of autoimmune encephalitis in children.
“With newly characterized conditions like autoimmune encephalitis, the lack of objective measures to support the clinical diagnosis makes arriving at the diagnosis difficult,” says Bethanie Morgan-Followell, MD, an attending pediatric neurologist in the Section of Neurology at Nationwide Children’s and senior author of the Pediatric Neurology study. “The clinical syndrome associated with anti-NMDA receptor antibodies is fairly well-defined. However, not so with the other neuronal surface antibodies and anti-GAD65—there is considerable overlap.”
According to Dr. Morgan-Followell, who is also director of the Neuroimmunology Clinic at Nationwide Children’s, the different types of autoimmune encephalitis syndromes have so much clinical overlap that ancillary testing is needed to tease out additional details that could determine a specific diagnosis.
“Our team conducted a retrospective study over a relatively long time-span – four years,” says Dr. Morgan-Followell of the study methods. “Based on chart reviews of 18 pediatric patients, we identified and compared clinical presentation, autoantibody status, MRI and EEG findings.”
The team found that pediatric patients with autoimmune encephalitis associated with either anti-NMDA receptor or anti-GAD65 antibodies had a narrow spectrum of brain MRI abnormalities. These abnormalities were mainly observed in the limbic structures of the brain, which play an important role in emotions and memories, among other functions.
EEG abnormalities, on the other hand, were found to be nonspecific regardless of antibody status. Specifically, the observed EEG abnormalities included abnormalities in the sleep architecture, or structure and pattern of sleep as it shifts between different stages of sleep. Of the 16 patients who had EEG studies, a novel finding was the occurrence of asynchrony or prolongation of sleep spindles, which are brief bursts of fast activity that are visible on an EEG during stage 2 sleep.
“There are a few known antibodies for autoimmune encephalitis, and we can test for those,” explains Dr. Morgan-Followell. “But it is very likely that we have yet to identify others. Even if new antibodies are identified, these may not be pathogenic—perhaps they are non-specific markers of inflammation.”
“All patients in our study cohort had abnormalities in either MRI or EEG, or both,” says Dr. Morgan-Followell, who is also an assistant professor of Clinical Pediatrics and Neurology at The Ohio State University College of Medicine. “The utility of these neurodiagnostic tools in the setting of autoimmune encephalitis is still unclear, and future large prospective studies are necessary to validate our observations, as well as to provide data on the sensitivity and specificity of these findings for pediatric autoimmune encephalitis.”
Study co-authors from Nationwide Children’s included Dara Albert, DO, pediatric neurologist; Amanda Berger-Weber, DO, clinical neurophysiology fellow; Jorge Vidaurre, MD, pediatric neurologist; Fatima Barbar-Smiley, MD, rheumatology fellow alumna; Rabheh Abdul Aziz, MD, rheumatology fellow; Kyla Driest, MD, rheumatologist; Sharon Bout-Tabaku, MD, interim chief of rheumatology; Lynne Ruess, MD, radiologist; and Jerome Rusin, MD, section chief of neuroradiology. Charles Pluto, MD, PhD, a diagnostic radiologist at the University of New Mexico, formerly at Nationwide Children’s, also collaborated on the study.
“Autoimmune encephalitis was only described about 10 years ago, but research has quickly progressed to identify numerous clinical phenotypes and various antibodies,” says E. Steve Roach, MD, chief of pediatric neurology and vice-chair of pediatrics at Nationwide Children’s. “This study combines authors from our neurology, rheumatology and radiology departments, demonstrating a good example of what interdepartmental collaboration in the clinical realm can yield.”
Albert DV, Pluto CP, Weber A, Vidaurre J, Barbar-Smiley F, Abdul Aziz R, Driest K, Bout-Tabaku S, Ruess L, Rusin JA, Morgan-Followell B. Utility of Neurodiagnostic Studies in the Diagnosis of Autoimmune Encephalitis in Children. Pediatric Neurology. 2016; 55:37-45.