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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.
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.
Surprising Result
The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum.
“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.
It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”
“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.
There was no association between iron accumulation and symptom severity as measured by SCAT scores.
Questions Remain
It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted.
The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.
Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.
Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.
“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”
Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain.
Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”
He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.
He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.
The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed.
A version of this article appeared on Medscape.com.
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.
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.
Surprising Result
The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum.
“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.
It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”
“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.
There was no association between iron accumulation and symptom severity as measured by SCAT scores.
Questions Remain
It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted.
The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.
Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.
Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.
“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”
Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain.
Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”
He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.
He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.
The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed.
A version of this article appeared on Medscape.com.
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.
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.
Surprising Result
The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum.
“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.
It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”
“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.
There was no association between iron accumulation and symptom severity as measured by SCAT scores.
Questions Remain
It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted.
The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.
Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.
Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.
“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”
Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain.
Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”
He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.
He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.
The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed.
A version of this article appeared on Medscape.com.