Steroid-Responsive, Post-infectious New Daily Persistent Headache With Mild Cerebrospinal Fluid Pleocytosis: A Case Report.

New daily persistent headache (NDPH) is a primary headache disorder characterized by a clearly remembered onset, with the headache becoming daily and unremitting within 24 hours and persisting for more than 3 months. Although antecedent infections have been reported as potential triggering events, the pathophysiology of post-infectious presentations of NDPH remains incompletely understood, and effective treatment options are limited. We report the case of a 42-year-old man who developed a continuous daily headache following a flu-like illness and was diagnosed with NDPH according to the International Classification of Headache Disorders, 3rd edition. Cerebrospinal fluid examination revealed mild pleocytosis, while neurological examination and neuroimaging findings were unremarkable. Intravenous methylprednisolone therapy, followed by a short course of oral corticosteroids, resulted in rapid and sustained complete resolution of the headache. This case suggests that inflammatory or immune-related mechanisms may contribute to headache persistence in a subset of patients with NDPH triggered by antecedent infection. However, responsiveness to corticosteroid therapy does not necessarily indicate the presence of ongoing active inflammation and may instead reflect reversible modulation of mechanisms involved in headache chronification. Further studies are required to clarify the pathophysiology of post-infectious NDPH and to identify patients who may benefit from targeted therapeutic approaches.