Editors' note: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine

Abstract

In “Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine,” Dominguez et al. studied iron deposition seen on MRI and serum markers of inflammation, endothelial dysfunction, and blood-brain barrier breakdown in 57 patients with episodic migraine, 55 patients with chronic migraine, and 25 headache-free controls. They found that patients with chronic migraine had significantly increased iron deposition in the periaqueductal gray (PAG) by MRI scanning as compared to those with episodic migraines and that patients with episodic migraines had more iron deposition in the PAG than controls. The response to these findings was mixed. Although Shubhakaran praised this “milestone article,” Gupta questioned the impact of both this study and previous studies evaluating the value of biomarkers in migraineurs. Welch noted that it was previously controversial to suggest that iron deposition in the PAG might correlate with the severity of migraine, but that study by Dominguez et al. convincingly supports this notion. Shubhakaran further commented that it is unclear whether iron deposition is a cause, effect, or correlate of migraine, but that it is evident that further work is needed to understand how to prevent and/or mitigate the effects of iron accumulation. Welch felt that although the cause of iron deposition remains unknown, it might be the result of damage from free radicals in the setting of breakdown in the blood-brain barrier and hyperoxia. Leira and Dominguez hypothesized that increased iron deposition may be indicative of structural changes to key nociceptive areas of the brain that result in chronic migraine. In light of the fact that migraine attack frequency can decrease in older patients despite increased iron deposition, Welch proposed that the effects of deposition may diminish later in life in the setting of fewer migraine triggers, such as less dynamic shifts in estrogen. Dominguez et al. concluded that further research is needed to assess the reversibility of iron deposition in the PAG. In “Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine,” Dominguez et al. studied iron deposition seen on MRI and serum markers of inflammation, endothelial dysfunction, and blood-brain barrier breakdown in 57 patients with episodic migraine, 55 patients with chronic migraine, and 25 headache-free controls. They found that patients with chronic migraine had significantly increased iron deposition in the periaqueductal gray (PAG) by MRI scanning as compared to those with episodic migraines and that patients with episodic migraines had more iron deposition in the PAG than controls. The response to these findings was mixed. Although Shubhakaran praised this “milestone article,” Gupta questioned the impact of both this study and previous studies evaluating the value of biomarkers in migraineurs. Welch noted that it was previously controversial to suggest that iron deposition in the PAG might correlate with the severity of migraine, but that study by Dominguez et al. convincingly supports this notion. Shubhakaran further commented that it is unclear whether iron deposition is a cause, effect, or correlate of migraine, but that it is evident that further work is needed to understand how to prevent and/or mitigate the effects of iron accumulation. Welch felt that although the cause of iron deposition remains unknown, it might be the result of damage from free radicals in the setting of breakdown in the blood-brain barrier and hyperoxia. Leira and Dominguez hypothesized that increased iron deposition may be indicative of structural changes to key nociceptive areas of the brain that result in chronic migraine. In light of the fact that migraine attack frequency can decrease in older patients despite increased iron deposition, Welch proposed that the effects of deposition may diminish later in life in the setting of fewer migraine triggers, such as less dynamic shifts in estrogen. Dominguez et al. concluded that further research is needed to assess the reversibility of iron deposition in the PAG.