Autoimmune neuroinflammatory disorders are among the most dramatic and interesting diseases in child neurology. They can induce substantial neurological and psychiatric symptoms with a thunderclap onset, and they can lead to permanent and severe disability. In addition, their etiologies are fascinating, as they are induced by disruptions in the relationship between the two most complex organ systems in the body – the nervous system and the immune system. Furthermore, entirely new diseases within the category of autoimmune neuroinflammatory diseases are being discovered at a rapid pace. Indeed, anti-NMDA receptor encephalitis and anti-MOG associated disorders (MOGAD), which are commonly diagnosed today, were unknown until recent years.
However, despite the importance of autoimmune neuroinflammatory diseases, many aspects about them remain unclear. What causes them? How can they be ideally treated? Why do some patients respond so much better to treatment than others? Dr. Grace Gombolay aims to shed light on the dark mysteries of pediatric autoimmune neuroinflammatory disorders (Figure 1).
Figure 1. Dr. Grace Gombolay examines MRI scans as she investigates biomarkers for pediatric neuroinflammatory disorders.
Dr. Gombolay is an assistant professor of pediatrics within the division of neurology at Emory University and at Children’s Healthcare of Atlanta. Her principal research goal is to identify biomarkers that can be used to diagnose neuroinflammatory disorders, identify their optimal treatment, and determine their prognosis.
Although still very early in her career, Dr. Gombolay has already made some important contributions and is poised to make many more. She established a biorepository with over 250 children with rare neuroinflammatory disorders at Emory University, which she later expanded into a multi-center prospective patient registry called “CONNECT” (CONquering Neuroinflammation and Epilepsies Consortium). This is the first such patient registry of pediatric neuroinflammatory disorders in the US.
Using CONNECT, Dr. Gombolay, along with Dr. Coral Stredny at Boston Children’s Hospital and their colleagues, have completed several important studies. In one study, Dr. Gombolay’s research team examined the importance of lesion location on clinical outcome in children with anti-NMDA receptor encephalitis. They found that lesion location plays an important role in outcome. In particular, frontal and occipital lobe lesions predicted a poor outcome. Why lesions in those particular lobes lead to worse outcomes than others remains unknown. Nevertheless, their work established lesion location as an important prognostic biomarker in anti-NMDA receptor encephalitis.
In a separate study, Dr. Gombolay’s team examined leptomeningeal enhancement as a distinguishing factor among neuroinflammatory diseases. Examining a large number of MRI studies from patients with anti-MOG associated disease (MOGAD), multiple sclerosis, and neuromyelitis optica spectrum disorders (NMOSD), they found that leptomeningeal enhancement is present in one-third of MOGAD cases, while it is virtually never present in cases of MS and NMOSD (Figure 2). Thus, her team has identified leptomeningeal enhancement as a neuroradiological biomarker for MOGAD.
Figure 2. Axial T2 FLAIR (left) and contrast-enhanced T1-weighted (right) images from patients with MOGAD (A, B, C, and D), multiple sclerosis (E and F), and neuromyelitis optica spectrum disorder (G and H). Leptomeningeal enhancement (arrow in B) is present only in some cases of MOGAD but not in MS or NMOSD. For more details, see Pediatric Neurology 2024; 153: 125-130.
Dr. Gombolay is well on her way toward a career of successful scientific achievement. However, her path has not been an easy one. The first six research grant applications that she submitted were all rejected. Several well-meaning advisors suggested she stop pursuing grants and abandon her scientific career. However, one wise advisor recognized her passion for science and stated that if she remained committed, her perseverance would eventually lead to success. Dr. Gombolay heeded that advice and is grateful for it. She has subsequently received nine research grants, including funding from the Pediatric Epilepsy Research Foundation (PERF) and National Institutes of Health (NIH).
Pediatric neuroinflammatory disorders are as scientifically intriguing and clinically demanding as anything we encounter in child neurology. Unraveling their complexity and devising more effective ways to diagnose and treat them will require dedication and tenacity. Because Grace Gombolay possesses those qualities in abundance, she will likely make many contributions to the field of pediatric neuroinflammatory disorders.