Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
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Abstract
Objective To study iron deposition in red nucleus (RN), globus pallidus (GP), and periaqueductal gray matter (PAG) as a potential biomarker of chronic migraine (CM) and its association with levels of biomarkers related to migraine pathophysiology.
Methods This case-control study included 112 patients with migraine (55 CM, 57 episodic migraine [EM]) and 25 headache-free controls. We analyzed iron deposition using 3T MRI and the NIH software platform ImageJ; we analyzed serum levels of markers of inflammation, endothelial dysfunction, and blood-brain barrier (BBB) disruption by ELISA in peripheral blood during interictal periods.
Results Patients with CM showed larger iron grounds volume in RN compared to patients with EM (70.2 ± 6.8 vs 25.5 ± 7.3 μL, p < 0.001) and controls (70.2 ± 6.8 vs 15.1 ± 10.8 μL, p < 0.001), as well as larger iron deposits in PAG compared to patients with EM (360.3 ± 6.5 vs 249.7 ± 6.9 μL, p < 0.001) and controls (360.3 ± 6.5 vs 168.6 ± 10.3 μL, p < 0.001). In PAG, differences were also significant between patients with EM and controls. No significant differences were obtained for GP. Receiver operating characteristic curves showed that the optimal threshold for iron volume was 15 μL in RN (80% sensitivity, 71% specificity) and 240 μL in PAG (93% sensitivity, 97% specificity). Iron grounds volume in PAG was correlated with higher plasma levels of soluble tumor necrosis factor–like WEAK (r = 0.395, p = 0.005) and cellular fibronectin (r = 0.294, p = 0.040).
Conclusions Patients with CM showed increased iron deposition in RN and PAG compared to patients with EM and controls. Iron grounds volume in PAG identified correctly patients with CM and was associated with elevated biomarkers of endothelial dysfunction and BBB disruption.
Glossary
- BBB=
- blood-brain barrier;
- BG=
- basal ganglia;
- CAMERA=
- Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis;
- cFn=
- cellular fibronectin;
- CGRP=
- calcitonin gene-related peptide;
- EM=
- episodic migraine;
- GP=
- globus pallidus;
- hs-CRP=
- high-sensitivity C-reactive protein;
- IL=
- interleukin;
- PAG=
- periaqueductal gray matter;
- PTX3=
- pentraxin 3;
- RN=
- red nucleus;
- ROI=
- region of interest;
- sTWEAK=
- soluble tumor necrosis factor–like WEAK;
- TGV=
- trigeminovascular;
- TNF-α=
- tumor necrosis factor-α
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
CME Course: NPub.org/cmelist
- Received August 27, 2018.
- Accepted in final form October 31, 2018.
- © 2019 American Academy of Neurology
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Letters: Rapid online correspondence
- Author response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
- Clara Domínguez, MD, Hospital Clínico Universitario de Santiago de Compostela
- Rogelio Leira, MD, PhD, Hospital Clínico Universitario de Santiago de Compostela
Submitted May 17, 2019 - Author response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
- Rogelio Leira, MD, PhD, Hospital Clínico Universitario de Santiago de Compostela
- Clara Dominguez, MD, Hospital Clínico Universitario de Santiago de Compostela
Submitted April 21, 2019 - Author response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
- Rogelio Leira, PhD, MD, Hospital Clínico Universitario de Santiago de Compostela
- Clara Domínguez, MD, Hospital Clínico Universitario de Santiago de Compostela
Submitted April 13, 2019 - Reader response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
- Kenneth M.A. Welch, Professor Emeritus, Division of Clinical Sciences,, Chicago Medical School, Rosalind Franklin University
Submitted April 06, 2019 - Reader response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
- Vinod Gupta, Physician, Migraine-Headache Institute, Gupta Medical Centre (New Delhi, India)
Submitted March 08, 2019 - Reader response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraine
- Khichar Shubhakaran, Neurology Professor, Dr. Sampurnanand Medical College (Jodhpur, India)
Submitted March 05, 2019
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Author response: Iron deposition in periaqueductal gray matter as a potential biomarker for chronic migraineRogelio Leira, Clara Domínguez et al.Neurology, February 04, 2020