MRI may predict worsening of rare brain inflammation disease

Pediatric anti-NMDA receptor autoimmune encephalitis (pNMDARE) is a very rare type of brain inflammation. The disease is characterized by a misdirected immune response creating antibodies against N-methyl-D-aspartate (NMDA) receptors. These antibodies disrupt normal brain signaling causing the brain to swell, and may result in psychiatric symptoms affecting thinking, memory, mood and consciousness—and that may lead to such behaviors as paranoia, hallucinations or aggression. Some patients affected by pNMDARE have worsening symptoms and poor outcomes, which may result in intensive care unit (ICU) admission, abnormal magnetic resonance imaging (MRI), a cerebrospinal fluid white blood cell count of less than 20, treatment lasting longer than four weeks, or a lack of improvement after four weeks. However, it is difficult for physicians to predict which patients will be impacted. To help answer this question, Grace Gombolay, MD, Pediatric Neurologist at Children’s and Assistant Professor of Pediatrics at Emory, was first author and principal investigator on a multicenter retrospective study of 175 patients from 11 institutions looking at whether brain MRI features may be used to predict poor outcomes, defined as three or more of the events described above. From a review of the imaging, Dr. Gombolay and her team of investigators found that children with lesions located in the brain’s frontal lobes (which control voluntary movement, language, memory, attention and judgment) or occipital lobes (responsible for visual processing) were more likely to have poor outcomes. They published the findings in the Journal of Neurology, Neuroimmunology and Neuroinflammation. “MRI could be used in the future to predict outcomes in children with pNMDARE and help guide neurologists on when to use more aggressive immune therapies for treatment,” said Dr. Gombolay. “But validation studies in other independent groups are needed before using MRI markers to guide treatment.” Diagnosis for pediatric anti-NMDA receptor autoimmune encephalitis is confirmed by a blood or spinal fluid test, which detects the antibodies. The disease affects less than one in 1 million children per year, primarily girls. It was not identified until 2007, and the exact cause, which may be a combination of child’s genes and their environment, is still unknown. Neurologists are currently aware that infections or tumors may trigger such a mistaken immune response. NMDA receptors are neurotransmitters highly involved in connections allowing for flexible brain communication, or synaptic plasticity, which experts believe is central to the formation of memory.