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Brain Iron Accumulation in Chronic Migraine: Pathophysiological Insights and Imaging Biomarkers for Personalized Therapy.

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Title: Brain Iron Accumulation in Chronic Migraine: Pathophysiological Insights and Imaging Biomarkers for Personalized Therapy.
Authors: Kikui, Shoji (AUTHOR), Danno, Daisuke (AUTHOR), Takeshima, Takao (AUTHOR), Chauhan, Anjali (AUTHOR)
Source: Acta Neurologica Scandinavica. 7/6/2026, Vol. 2026, p1-11. 11p.
Subjects: Migraine, Periaqueductal gray matter, Individualized medicine, Pathological physiology, Magnetic resonance imaging, Computer-assisted image analysis (Medicine), Magnetic susceptibility
Abstract: Background/Aim: Chronic migraine (CM) is a disabling neurological disorder characterized by persistent alterations in central pain modulation pathways. Emerging evidence suggests that abnormal iron accumulation in deep brain nuclei, particularly the periaqueductal gray (PAG), may represent a potential pathophysiological mechanism and an imaging biomarker of disease progression. This review is aimed at synthesizing current knowledge on brain iron metabolism in migraine and its clinical relevance. Methods: We narratively reviewed the literature on conventional and advanced magnetic resonance imaging (MRI) techniques, including T2‐weighted imaging, susceptibility‐weighted imaging, and quantitative susceptibility mapping (QSM), and analyzed their findings regarding iron deposition in patients with migraine, especially CM. Results: Multiple studies have demonstrated increased iron accumulation in the PAG, red nucleus, and nucleus accumbens in CM, correlating with disease duration, medication overuse, and poor treatment responsiveness. QSM has emerged as a sensitive method for quantifying regional iron loads. Three hypotheses have been proposed: iron accumulation as a consequence of repeated attacks, as a causal factor in chronification, or as a comorbid process linked to shared risk factors. Brain iron burden may be associated with therapeutic response to onabotulinumtoxinA and calcitonin gene‐related peptide‐targeted therapies. Discussion: At the molecular level, iron‐mediated oxidative damage through ferritinophagy and ferroptosis may contribute to neuronal dysfunction in pain modulatory circuits. While inconsistencies exist across studies, converging evidence supports the importance of iron dysregulation in migraine chronification. Conclusion: Brain iron accumulation may represent a promising imaging biomarker and potential therapeutic target in CM. Further longitudinal and mechanistic studies are warranted to clarify its causal role and to validate iron‐based metrics for personalized treatment strategies. [ABSTRACT FROM AUTHOR]
Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Label: Title
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  Data: Brain Iron Accumulation in Chronic Migraine: Pathophysiological Insights and Imaging Biomarkers for Personalized Therapy.
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  Data: <searchLink fieldCode="AR" term="%22Kikui%2C+Shoji%22">Kikui, Shoji</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Danno%2C+Daisuke%22">Danno, Daisuke</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Takeshima%2C+Takao%22">Takeshima, Takao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chauhan%2C+Anjali%22">Chauhan, Anjali</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Acta+Neurologica+Scandinavica%22">Acta Neurologica Scandinavica</searchLink>. 7/6/2026, Vol. 2026, p1-11. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Migraine%22">Migraine</searchLink><br /><searchLink fieldCode="DE" term="%22Periaqueductal+gray+matter%22">Periaqueductal gray matter</searchLink><br /><searchLink fieldCode="DE" term="%22Individualized+medicine%22">Individualized medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Pathological+physiology%22">Pathological physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Magnetic+resonance+imaging%22">Magnetic resonance imaging</searchLink><br /><searchLink fieldCode="DE" term="%22Computer-assisted+image+analysis+%28Medicine%29%22">Computer-assisted image analysis (Medicine)</searchLink><br /><searchLink fieldCode="DE" term="%22Magnetic+susceptibility%22">Magnetic susceptibility</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background/Aim: Chronic migraine (CM) is a disabling neurological disorder characterized by persistent alterations in central pain modulation pathways. Emerging evidence suggests that abnormal iron accumulation in deep brain nuclei, particularly the periaqueductal gray (PAG), may represent a potential pathophysiological mechanism and an imaging biomarker of disease progression. This review is aimed at synthesizing current knowledge on brain iron metabolism in migraine and its clinical relevance. Methods: We narratively reviewed the literature on conventional and advanced magnetic resonance imaging (MRI) techniques, including T2‐weighted imaging, susceptibility‐weighted imaging, and quantitative susceptibility mapping (QSM), and analyzed their findings regarding iron deposition in patients with migraine, especially CM. Results: Multiple studies have demonstrated increased iron accumulation in the PAG, red nucleus, and nucleus accumbens in CM, correlating with disease duration, medication overuse, and poor treatment responsiveness. QSM has emerged as a sensitive method for quantifying regional iron loads. Three hypotheses have been proposed: iron accumulation as a consequence of repeated attacks, as a causal factor in chronification, or as a comorbid process linked to shared risk factors. Brain iron burden may be associated with therapeutic response to onabotulinumtoxinA and calcitonin gene‐related peptide‐targeted therapies. Discussion: At the molecular level, iron‐mediated oxidative damage through ferritinophagy and ferroptosis may contribute to neuronal dysfunction in pain modulatory circuits. While inconsistencies exist across studies, converging evidence supports the importance of iron dysregulation in migraine chronification. Conclusion: Brain iron accumulation may represent a promising imaging biomarker and potential therapeutic target in CM. Further longitudinal and mechanistic studies are warranted to clarify its causal role and to validate iron‐based metrics for personalized treatment strategies. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1155/ane/1977026
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        Text: English
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      – SubjectFull: Migraine
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      – SubjectFull: Periaqueductal gray matter
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      – SubjectFull: Individualized medicine
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      – SubjectFull: Pathological physiology
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      – SubjectFull: Magnetic resonance imaging
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      – SubjectFull: Computer-assisted image analysis (Medicine)
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      – SubjectFull: Magnetic susceptibility
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      – TitleFull: Brain Iron Accumulation in Chronic Migraine: Pathophysiological Insights and Imaging Biomarkers for Personalized Therapy.
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              Text: 7/6/2026
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              Y: 2026
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