Periaqueductal gray matter echogenicity: An irreversible marker of chronic migraine?

AimAlthough periaqueductal grey matter (PAG), assessed by transcranial sonography, has been proposed as a biomarker of migraine chronification, its longitudinal evolution remains unknown. This study aimed to evaluate whether changes in clinical diagnosis-from chronic migraine to episodic migraine (CM-EM) or from episodic migraine to chronic migraine (EM-CM)-were associated with modifications in PAG echogenicity.MethodsIn a prospective longitudinal cohort study we reanalysed a cohort of 115 participants (65 patients with migraine and 50 controls) previously assessed in a baseline study. The follow-up was performed three years after the initial evaluation, collecting demographic, clinical (migraine-related), and sonographic variables.ResultsNinety-four of the 115 participants were re-evaluated at the longitudinal follow-up. Patients who converted from episodic to chronic migraine (EM-CM, n = 3) showed a significantly larger PAG area (0.22 [0.16-0.23] cm² vs. 0.13 [0.12-0.16] cm²; p = 0.043), a greater reduction in PAG echogenicity (-0.52 [-0.52 to -0.24] vs. -0.03 [-0.21 to 0.17]; p = 0.008), and higher heterogeneity (33.88 [31.85-36.72] vs. 26.67 [23.33-38.9]; p = 0.0344) at baseline compared with patients who remained episodic at the follow-up assessment (n = 18). Among patients with chronic migraine at baseline, no significant differences in PAG area, heterogeneity, or echogenicity intensity were observed between those who remained chronic and those who were classified as episodic migraine at follow-up.ConclusionPatients with chronic migraine who clinically improved (CM-EM) did not show relevant between-assessment differences in the previously described PAG alterations, suggesting the persistence of these alterations despite clinical improvement. In contrast, the small group of patients who underwent EM-CM transformation exhibited increased PAG heterogeneity and area at the follow-up assessment. Further studies with a larger sample size should be performed to confirm these results.