Abstract
Building on Part 1’s exploration of Chronic Inflammatory Response Syndrome (CIRS) in pediatric neuroimmune disorders, this article (part 2 in a series of four) examines Lyme disease and its associated co-infections as infectious drivers of neuroinflammation overlapping with autism spectrum disorder (ASD). In a cohort of 1,722 children with treatment-resistant ASD and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS/PANDAS), all met clinical CIRS criteria through bedside diagnosis, with notable improvements in cognition, motor skills, and gastrointestinal function following CIRS-directed therapies. Within this cohort, 47 children living in tick-endemic regions presented with Lyme-specific features—including facial palsy, joint pain and swelling, difficulty chewing, cyclical fevers, and low muscle tone. They were diagnosed clinically according to CDC guidelines, supported by parental reports of bull’s-eye rashes or tick attachments. Borrelia burgdorferi and co-transmitted pathogens such as Babesia microti and Bartonella henselae can sustain immune dysregulation through mechanisms including blood–brain barrier disruption, Th17/Treg imbalance, complement activation, mitochondrial dysfunction, and microglial priming, contributing to cognitive, behavioral, and developmental impairments. Clinically, these children exhibited fatigue, attention deficits, anxiety, obsessive-compulsive behaviors, and developmental regression—features that complicate differential diagnosis with ASD. Conventional serologic testing shows limited sensitivity in early or chronic cases, underscoring the importance of clinical evaluation. While early antibiotic therapy remains the standard of care, adjunctive strategies adapted from CIRS protocols—including immune modulation and environmental remediation—appear to improve outcomes. As the second article in a four-part series on pediatric neuroimmune conditions, this work highlights infectious contributions to neurodevelopmental disruption and sets the stage for Part 3’s focus on herbal therapeutics for CIRS, the primary driver of illness in this cohort.