Objective: To interrogate brain iron accumulation using magnetic resonance T imaging in acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI) and to examine associations between iron accumulation with headache frequency, number of mTBIs, post-concussion symptom severity, and time since TBI.
Background: We hypothesized that brain iron accumulation, a marker of neural injury, would be present in PTH and that it would correlate with measures of PTH and mTBI severity.
Design/methods: Sixty participants with acute PTH and 60 age-matched healthy controls (HC) underwent 3T brain magnetic resonance imaging (T maps). T differences were determined using age-matched paired t-tests. For the PTH group, T correlations with headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) severity scale scores were studied using multiple linear regression.
Results: Lower T values in PTH participants relative to HC were observed in the right supramarginal area, left occipital, bilateral precuneus, right cuneus, right cerebellum, right temporal, bilateral caudate, genu of the corpus callosum, right anterior cingulate cortex and right rolandic operculum (p<0.001). Within PTH subjects, there were positive correlations between lifetime mTBIs and iron accumulation in the right gyrus rectus and right putamen, the time since most recent mTBI and Tin the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, right cerebellum, and between headache frequency with T in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum.
Conclusions: Iron accumulation is observed in brain regions of PTH participants relative to HC. Positive correlations of iron accumulation with headache frequency, number of lifetime mTBIs and time since mTBI suggest that iron accumulation is a biomarker of mTBI and PTH, potentially informing underlying pathophysiology. Dr. Nikolova has nothing to disclose. Dr. Chong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for HCOP. The institution of Dr. Chong has received research support from AMGEN. The institution of Dr. Chong has received research support from Department of Defense. The institution of Dr. Chong has received research support from NIH. An immediate family member of Dr. Chong has received intellectual property interests from a discovery or technology relating to health care. Prof. Li has nothing to disclose. Dr. Wu has nothing to disclose. Gina Dumkrieger has received personal compensation for serving as an employee of Mayo Clinic. The institution of Gina Dumkrieger has received research support from NIH. The institution of Gina Dumkrieger has received research support from DOD. The institution of Gina Dumkrieger has received research support from AMGEN. Katherine Ross has nothing to disclose. Visar Berisha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Visar Berisha has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boehringer Ingelheim. Visar Berisha has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Aural Analytics. Visar Berisha has received stock or an ownership interest from Aural Analytics. The institution of Visar Berisha has received research support from Boheringer Ingelheim. Visar Berisha has received intellectual property interests from a discovery or technology relating to health care. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Miller Medical. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for eNeura. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Allergan. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Schwedt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Schwedt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biodelivery Science. Dr. Schwedt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Linpharma. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Dr. Schwedt has received personal compensation in the range of $0-$499 for serving as a Consultant for Amgen. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scilex. Dr. Schwedt has stock in Aural Analytics. Dr. Schwedt has stock in Nocira. The institution of Dr. Schwedt has received research support from Amgen. The institution of Dr. Schwedt has received research support from National Institutes of Health. The institution of Dr. Schwedt has received research support from United States Department of Defense. The institution of Dr. Schwedt has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Schwedt has received research support from SPARK Neuro. The institution of Dr. Schwedt has received research support from Henry Jackson Foundation. Dr. Schwedt has received intellectual property interests from a discovery or technology relating to health care. Dr. Schwedt has received publishing royalties from a publication relating to health care.
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