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A New Biomarker of Brain Injury?


 

Posttraumatic headache (PTH) is associated with an increase in iron accumulation in certain brain regions , notably those involved in the pain network, early research shows.

Investigators found positive correlations between iron accumulation and headache frequency, number of lifetime mild traumatic brain injuries (mTBIs), and time since last mTBI.

The findings come on the heels of previous research showing patients with iron accumulation in certain brain regions don’t respond as well to treatment, study investigator, Simona Nikolova, PhD, assistant professor of neurology, Mayo Clinic, Phoenix, Arizona, told this news organization.

“This is really important, and doctors need to be aware of it. If you have a patient who is not responding to treatment, then you know what to look at,” she said.

The findings (Abstract #3379) will be presented on April 15 at the American Academy of Neurology (AAN) 2024 Annual Meeting.

Dose Effect

The study included 60 people with acute PTH due to mTBI. Most were White, and almost half had sustained a concussion due to a fall, with about 30% injured in a vehicle accident and a smaller number injured during a fight.

The mean number of lifetime mTBIs was 2.4, although participants had sustained as many as five or six and as few as one. The mean time from the most recent mTBI was 25 days, and the mean score on the Sport Concussion Assessment Tool (SCAT), which measures postconcussion symptom severity, was 29.

Most in the mTBI group (43) had migraine or probable migraine, and 14 had tension-type headaches. Mean headache frequency was 81%.

Researchers matched these patients with 60 controls without concussion or headache. Because iron accumulation is age-related, they tried to eliminate this covariant by pairing each participant with mTBI with an age- and sex-matched control.

All participants underwent a type of brain MRI known as T2* weighted sequence that can identify brain iron accumulation, a marker of neural injury.

Investigators found that the PTH group had significantly higher levels of iron accumulation in several areas of the brain, most of which are part of a “pain network” that includes about 63 areas of the brain, Dr. Nikolova said.

The study wasn’t designed to determine how much more iron accumulation mTBI patients had vs controls.

“We can’t say it was twice as much or three times as much; we can only say it was significant. Measuring concentrations in PTH patients and comparing that with controls is something we haven’t don’t yet,” said Dr. Nikolova.

Areas of the brain with increased iron accumulation, included the periaqueductal gray (PAG), anterior cingulated cortex, and supramarginal gyrus.

Research suggests patients with migraine who have elevated levels of iron in the PAG have a poorer response to botulinum toxin treatment. An earlier study by the same team showed a poorer response to the calcitonin gene-related peptide inhibitor erenumab in migraine patients with elevated iron in the PAG.

Researchers discovered that those with more lifetime TBIs had higher iron accumulation in the right gyrus rectus and right putamen vs those with fewer injuries and that headache frequency was associated with iron accumulation in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum.

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