Neuroimaging Findings and Treatment Update for Neuroinflammation, Autoinflammation, Splenomegaly, and Anemia, a Novel Autoinflammatory Disorder Caused by Bi-Allelic Variants in IRAK4.

Neuroinflammation, autoinflammation, splenomegaly, and anemia (NASA) is a newly described autoinflammatory disorder caused by bi-allelic variants in the interleukin receptor-associated kinase 4 gene, IRAK4. Since our first description of the disorder in 2023, we now report that all 5 cases from 2 unrelated kindreds have developed severe neuroinflammation that is resistant to systemic immunosuppressive treatment. In these 5 individuals, we describe the chronology of clinical features and their correlation with neuroimaging findings, which were notable for a "waxing and waning" pattern of neuroinflammation with an increasing inflammatory burden and areas of atrophy or parenchymal calcifications even at first clinical presentation. We highlight the clinical and therapeutic challenges and provide a commentary on the likely pathogenesis of neuroinflammation in NASA driven by CNS production of interleukin-6, and describe the neuroradiologic features that differentiate this rare syndrome from the more common differential diagnoses of autoimmune or infectious encephalitis. These cases emphasize that neurologic involvement in inborn errors of immunity may be underestimated and, therefore, we advocate for a high index of suspicion in all patients with an inflammatory phenotype.