Thinking Outside of the MOGAD Box: When Does CNS-Hemophagocytic Lymphohistiocytosis Make More Sense?

Neuroinflammatory syndromes in children often present with overlapping clinical, radiological and immunological features, posing significant diagnostic challenges. We describe two pediatric patients with acute neuroinflammatory presentations who fulfilled criteria for a well-recognized antibody-associated demyelinating disorder but also demonstrated clinical and laboratory features suggestive of a broader hyperinflammatory process. These cases underscore the diagnostic complexity when systemic and central nervous system inflammation coexist and highlight the importance of maintaining a broad differential diagnosis. Clinicians should be aware that antibody positivity does not preclude alternative or coexisting diagnoses and that failure to recognize hyperinflammatory syndromes may delay appropriate therapy.