Pediatric New Daily Persistent Headache: Integrating Novel Research Methods to Support and Delineate Evolving Clinical Phenotypes

Pediatric new daily persistent headache (NDPH) is a clinically defined headache subtype that remains controversial due to a lack of unique and objective mechanistic features. For many headache subtypes, different, and sometimes unique, patterns of structural and functional changes can be observed in the brain, supporting a unique role for neuroimaging in identifying the presence and type of headache experienced. To date, there has been little research into pediatric NDPH and how it may have a unique mechanism relative to other headache subtypes. We review published research that addressed structural and functional neuroimaging in persons with NDPH. We found that research to date supports differences in both brain structure and function in persons with NDPH relative to healthy controls. Such differences reflect both cortical and sub-cortical regions of the brain. No studies to date have evaluated brain data between persons with NDPH and other headache subtypes. We discuss application of machine learning and artificial intelligence to validate NDPH as a unique headache diagnosis. We believe that future work pursuing both neuroimaging alongside machine learning can help inform the classification and differential diagnosis of pediatric patients with NDPH from other chronic headache conditions.