Systemic Inflammation Markers in Migraine: A Cross‐Sectional Study

Background Neuroinflammatory and systemic immune mechanisms are increasingly recognized as contributors to migraine pathophysiology. However, peripheral markers of inflammation remain underexplored. This study aimed to evaluate systemic immune alterations in patients with migraine through complete blood count (CBC) parameters and derived inflammatory indices, comparing findings with healthy controls (HCs). Methods We conducted a cross‐sectional analysis of peripheral blood samples, assessing leukocyte subtypes including absolute and relative (percentage‐%) values, hemoglobin, and platelet levels. Inflammatory indices, including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII), were calculated. Migraine features were collected. Results A total of 409 subjects were included: 179 HCs, 194 with episodic migraine (EM), and 36 with chronic migraine (CM). Regarding inflammatory indices, SII significantly differed among EM, CM, and HCs ( p = 0.024). In particular, in post hoc analyses, it was significantly higher in CM (514.20 ± 250.57) vs. HCs (423.14 ± 221.69) ( p = 0.019) and in CM compared to EM (448.28 ± 266.53, p = 0.044). Similarly, neutrophil% significantly differed among the three groups ( p = 0.022), and was higher in patients with CM (58.69 ± 9.57) vs. HCs (54.81 ± 8.86, p = 0.019) and in patients with CM vs. EM (55.39 ± 9.77, p = 0.016). Lymphocyte% differed among the three groups ( p = 0.047), and it was lower in CM (31.51 ± 8.27) vs. HCs (34.55 ± 8.24, p = 0.047). Conclusions Systemic immune dysregulation appears to be associated with migraine, particularly CM. Alterations in neutrophil and lymphocyte distributions, as well as increased SII, may represent peripheral correlates of central neuroinflammation. These findings suggest that simple, routinely available blood‐derived markers could help identify inflammatory endophenotypes in migraine, warranting validation in larger, prospective studies.