Excessive iron accumulation in the striatum associated with addictive behaviors of medication-overuse headache: a prospective study.

BACKGROUND

Abnormal iron deposition may be a biomarker for a disrupted central antinociceptive neuronal network, and the relationship between iron deposition and the pathophysiological mechanisms of chronic migraine (CM) with medication overuse (MOH) remains unclear. We investigated iron deposition in the deep gray matter (DGM) of the brain in CM patients with and without MOH using quantitative susceptibility mapping (QSM).

METHODS

Forty-eight healthy controls (HCs) and 69 CM patients (36 with MOH; 33 without MOH) were recruited. QSM data were acquired using a 3.0 T Magnetic resonance imaging (MRI). Regions of interest (ROI) in the DGM, including the bilateral caudate, putamen, globus pallidus (GP), hippocampus, nucleus accumbens, and amygdala, were segmented from the T1-weighted images (T1WI) of the whole brain of each individual patient using FreeSurfer. QSM images were registered to T1WI. QSM values within each ROI were extracted and compared between CM and HCs, as well as between CM with MOH and CM without MOH. Correlations between QSM values and clinical assessment scale scores were calculated. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of QSM values in these DGM for detecting CM and CM with MOH.

RESULTS

Compared to HCs, CM patients exhibited increased iron deposition in the caudate (p = 0.013) and putamen (p < 0.001). In the CM without MOH group, headache duration correlated positively with iron deposition in the caudate (r = 0.502, p = 0.010) and putamen (r = 0.514, p = 0.009). CM with MOH patients showed greater iron deposition in the caudate (p < 0.001), putamen (p < 0.001), and GP (p = 0.049) than those without MOH, with medication use frequency correlating positively with iron deposition in the caudate (r = 0.427, p = 0.023) and putamen (r = 0.445, p = 0.018). ROC curve analysis indicated that the caudate (AUC = 0.736) and putamen (AUC = 0.729) exhibited high sensitivity and specificity in diagnosing CM with MOH.

CONCLUSIONS

CM patients with MOH had excessive iron deposition in basal ganglia regions, including the caudate, putamen, and GP, which may be related to the medication overuse behavior. Iron deposition in the caudate and putamen may be a potential biomarker for CM with MOH. These findings provide insight into the common pathophysiological mechanisms underlying MOH and potential addiction.