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Iron Deposition in Pain-Regulatory Nuclei in Episodic Migraine and Chronic Daily Headache by MRI

Authors

  • Stewart J. Tepper MD,

    Corresponding author
    1. From the Cleveland Clinic – Headache Center, Cleveland, OH, USA (S.J. Tepper, M.J. Stillman, and M. Horvat); Cleveland Clinic – Imaging Institute, Neuroradiology, Cleveland, OH, USA (M.J. Lowe, E. Beall, M.D. Phillips, and S.E. Jones); Siemens – MR R&D Research Collaborations, Solon, OH, USA (K. Liu).
      S.J. Tepper, Cleveland Clinic – Headache Center, C21, 9500 Euclid Avenue, Cleveland, OH 44195, USA, email: sjtepper@gmail.com
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  • Mark J. Lowe PhD,

    1. From the Cleveland Clinic – Headache Center, Cleveland, OH, USA (S.J. Tepper, M.J. Stillman, and M. Horvat); Cleveland Clinic – Imaging Institute, Neuroradiology, Cleveland, OH, USA (M.J. Lowe, E. Beall, M.D. Phillips, and S.E. Jones); Siemens – MR R&D Research Collaborations, Solon, OH, USA (K. Liu).
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  • Erik Beall PhD,

    1. From the Cleveland Clinic – Headache Center, Cleveland, OH, USA (S.J. Tepper, M.J. Stillman, and M. Horvat); Cleveland Clinic – Imaging Institute, Neuroradiology, Cleveland, OH, USA (M.J. Lowe, E. Beall, M.D. Phillips, and S.E. Jones); Siemens – MR R&D Research Collaborations, Solon, OH, USA (K. Liu).
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  • Micheal D. Phillips MD,

    1. From the Cleveland Clinic – Headache Center, Cleveland, OH, USA (S.J. Tepper, M.J. Stillman, and M. Horvat); Cleveland Clinic – Imaging Institute, Neuroradiology, Cleveland, OH, USA (M.J. Lowe, E. Beall, M.D. Phillips, and S.E. Jones); Siemens – MR R&D Research Collaborations, Solon, OH, USA (K. Liu).
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  • Kecheng Liu PhD,

    1. From the Cleveland Clinic – Headache Center, Cleveland, OH, USA (S.J. Tepper, M.J. Stillman, and M. Horvat); Cleveland Clinic – Imaging Institute, Neuroradiology, Cleveland, OH, USA (M.J. Lowe, E. Beall, M.D. Phillips, and S.E. Jones); Siemens – MR R&D Research Collaborations, Solon, OH, USA (K. Liu).
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  • Mark J. Stillman MD,

    1. From the Cleveland Clinic – Headache Center, Cleveland, OH, USA (S.J. Tepper, M.J. Stillman, and M. Horvat); Cleveland Clinic – Imaging Institute, Neuroradiology, Cleveland, OH, USA (M.J. Lowe, E. Beall, M.D. Phillips, and S.E. Jones); Siemens – MR R&D Research Collaborations, Solon, OH, USA (K. Liu).
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  • Mary Horvat BA,

    1. From the Cleveland Clinic – Headache Center, Cleveland, OH, USA (S.J. Tepper, M.J. Stillman, and M. Horvat); Cleveland Clinic – Imaging Institute, Neuroradiology, Cleveland, OH, USA (M.J. Lowe, E. Beall, M.D. Phillips, and S.E. Jones); Siemens – MR R&D Research Collaborations, Solon, OH, USA (K. Liu).
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  • Stephen E. Jones MD

    1. From the Cleveland Clinic – Headache Center, Cleveland, OH, USA (S.J. Tepper, M.J. Stillman, and M. Horvat); Cleveland Clinic – Imaging Institute, Neuroradiology, Cleveland, OH, USA (M.J. Lowe, E. Beall, M.D. Phillips, and S.E. Jones); Siemens – MR R&D Research Collaborations, Solon, OH, USA (K. Liu).
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  • Conflict of Interest: Stewart J. Tepper serves as a consultant, on the scientific advisory board, and/or on the speakers bureau for Allergan, GSK, Helsinn, Merck, MAP, Nautilus, NuPathe, Zogenix. He received research grants (no personal compensation) from ATI, GSK, MAP, and Merck. Kechung Liu: Dr. Liu received personal compensation from Siemens as an employee, and Merck supported this study (no personal compensation). Stephen Jones: Merck supported this study (no personal compensation). Micheal Phillips: Stock Options Description: Dr. Phillips has the right to receive royalty payments for inventions or discoveries related to IntElect Medical Inc. Research Support Description: Monteris Medical, Medtronic, Merck for this study (no personal compensation). Mark Stillman: Disclosure: M. Stillman, MD served on the Speaker's Bureaus for GlaxoSmithKline, Pfizer and Merck pharmaceutical companies. He also received consulting fees from Capnea Inc. Research Support Description: M. Stillman, MD and members of his center received financial support for research activities from the following pharmaceutical companies: GlaxoSmithKline, Merck, and MAP. Mary Horvat: Research Support Description ATI, GSK, MAP, Merck, Nupathe, and Zogenix (no personal compensation). Mark Lowe: Dr. Lowe has the right to receive royalty payments for inventions or discoveries related to IntElect Medical Inc. Research Support Description Merck for this study (no personal compensation). Erik Beall: Research support for this study: Merck (no personal compensation). No other disclosures.

S.J. Tepper, Cleveland Clinic – Headache Center, C21, 9500 Euclid Avenue, Cleveland, OH 44195, USA, email: sjtepper@gmail.com

Abstract

Background.— Progression of migraine toward a more disabling chronic form of at least 15 days/month is linked with frequency of attacks. Magnetic resonance imaging (MRI) findings of iron accumulation in the brain, especially in periaqueductal gray and red nucleus, have been correlated with both duration of illness and frequency of attacks.

Methods.— This study therefore evaluated iron deposition as measured with MRI in basal ganglia and pain regulatory nuclei in neurologically healthy control volunteers and in patients with various migraine subtypes: episodic migraine (n = 10) with (n = 4) or without aura (n = 6), and chronic daily headache (n = 11), including medication overuse headache (MOH, n = 8), chronic tension-type headache (n = 1), and primary chronic migraine (n = 2). The goal was to assess differences in iron deposition among migraine subtypes and controls in the hopes of linking the by-products of frequent attacks or long duration of illness with these changes.

Results.— The study sought to evaluate the tradeoff between sensitivity and specificity in T2 imaging of patients with migraine, and found that only T2 imaging in the globus pallidus was able to distinguish between episodic and chronic migraine, suggesting that this technique may be the most appropriate to assess migraine frequency. Patients with MOH did not demonstrate T2′ shortening.

Conclusions.— Because iron accumulation should cause shortening of both T2 and T2′, although the lack of significance in observed T2′ difference could be due to increased variance in T2′ the measurement, these results suggest that a mechanism other than increased iron deposition may play a role in the genesis or pathophysiology of MOH.

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