Migraine ICYMI

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

A version of this article first appeared on Medscape.com.

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

A version of this article first appeared on Medscape.com.

On Oct. 5, 2022, at 10:24 a.m., Chris Nowinski, PhD, cofounder of the Boston-based Concussion Legacy Foundation (CLF), was in his home office when the email came through. For the first time, the National Institutes of Health (NIH) acknowledged there was a causal link between repeated blows to the head and chronic traumatic encephalopathy (CTE).

“I pounded my desk, shouted YES! and went to find my wife so I could pick her up and give her a big hug,” he recalled. “It was the culmination of 15 years of research and hard work.”

Robert Cantu, MD, who has been studying head trauma for 50+ years and has published more than 500 papers about it, compares the announcement to the 1964 Surgeon General’s report that linked cigarette smoking with lung cancer and heart disease. With the NIH and the Centers of Disease Control and Prevention (CDC) now in agreement about the risks of participating in impact sports and activities, he said, “We’ve reached a tipping point that should finally prompt deniers such as the NHL, NCAA, FIFA, World Rugby, the International Olympic Committee, and other [sports organizations] to remove all unnecessary head trauma from their sports.”

“A lot of the credit for this must go to Chris,” added Dr. Cantu, medical director and director of clinical research at the Cantu Concussion Center at Emerson Hospital in Concord, Mass. “Clinicians like myself can reach only so many people by writing papers and giving speeches at medical conferences. For this to happen, the message needed to get out to parents, athletes, and society in general. And Chris was the vehicle for doing that.”

Dr. Nowinski didn’t set out to be the messenger. He played football at Harvard in the late 1990s, making second-team All-Ivy as a defensive tackle his senior year. In 2000, he enrolled in Killer Kowalski’s Wrestling Institute and eventually joined Vince McMahon’s World Wrestling Entertainment (WWE).

There he played the role of 295-pound villain “Chris Harvard,” an intellectual snob who dressed in crimson tights and insulted the crowd’s IQ. “Roses are red. Violets are blue. The reason I’m talking so slowly is because no one in [insert name of town he was appearing in] has passed grade 2!”

“I’d often apply my education during a match,” he wrote in his book, “Head Games: Football’s Concussion Crisis.“ In a match in Bridgeport, Conn., I assaulted [my opponent] with a human skeleton, ripped off the skull, got down on bended knee, and began reciting Hamlet. Those were good times.”

Those good times ended abruptly, however, during a match with Bubba Ray Dudley at the Hartford Civic Center in Connecticut in 2003. Even though pro wrestling matches are rehearsed, and the blows aren’t real, accidents happen. Mr. Dudley mistakenly kicked Dr. Nowinski in the jaw with enough force to put him on his back and make the whole ring shake.

“Holy shit, kid! You okay?” asked the referee. Before a foggy Dr. Nowinski could reply, 300-pound Mr. Dudley crashed down on him, hooked his leg, and the ref began counting, “One! Two! …” Dr. Nowinski instinctively kicked out but had forgotten the rest of the script. He managed to finish the match and stagger backstage.

His coherence and awareness gradually returned, but a “throbbing headache” persisted. A locker room doctor said he might have a concussion and recommended he wait to see how he felt before wrestling in Albany, N.Y., the next evening.

The following day the headache had subsided, but he still felt “a little strange.” Nonetheless, he told the doctor he was fine and strutted out to again battle Bubba Ray, this time in a match where he eventually got thrown through a ringside table and suffered the Dudley Death Drop. Afterward, “I crawled backstage and laid down. The headache was much, much worse.”
 

An event and a process

Dr. Nowinski continued to insist he was “fine” and wrestled a few more matches in the following days before finally acknowledging something was wrong. He’d had his bell rung numerous times in football, but this was different. Even more worrisome, none of the doctors he consulted could give him any definitive answers. He finally found his way to Emerson Hospital, where Dr. Cantu was the chief of neurosurgery. 

“I remember that day vividly,” said Dr. Cantu. “Chris was this big, strapping, handsome guy – a hell of an athlete whose star was rising. He didn’t realize that he’d suffered a series of concussions and that trying to push through them was the worst thing he could be doing.”

Concussions and their effects were misunderstood by many athletes, coaches, and even physicians back then. It was assumed that the quarter inch of bone surrounding the adult brain provided adequate protection from common sports impacts and that any aftereffects were temporary. A common treatment was smelling salts and a pat on the back as the athlete returned to action.

However, the brain floats inside the skull in a bath of cerebral fluid. Any significant impact causes it to slosh violently from side to side, damaging tissue, synapses, and cells resulting in inflammation that can manifest as confusion and brain fog.

“A concussion is actually not defined by a physical injury,” explained Dr. Nowinski, “but by a loss of brain function that is induced by trauma. Concussion is not just an event, but also a process.” It’s almost as if the person has suffered a small seizure.

Fortunately, most concussion symptoms resolve within 2 weeks, but in some cases, especially if there’s been additional head trauma, they can persist, causing anxiety, depression, anger, and/or sleep disorders. Known as postconcussion syndrome (PCS), this is what Dr. Nowinski was unknowingly suffering from when he consulted Dr. Cantu.

In fact, one night it an Indianapolis hotel, weeks after his initial concussion, he awoke to find himself on the floor and the room in shambles. His girlfriend was yelling his name and shaking him. She told him he’d been having a nightmare and had suddenly started screaming and tearing up the room. “I didn’t remember any of it,” he said.

Dr. Cantu eventually advised Dr. Nowinski against ever returning to the ring or any activity with the risk for head injury. Research shows that sustaining a single significant concussion increases the risk of subsequent more-severe brain injuries.

“My diagnosis could have sent Chris off the deep end because he could no longer do what he wanted to do with this life,” said Dr. Cantu. “But instead, he used it as a tool to find meaning for his life.”

Dr. Nowinski decided to use his experience as a teaching opportunity, not just for other athletes but also for sports organizations and the medical community.

His book, which focused on the NFL’s “tobacco-industry-like refusal to acknowledge the depths of the problem,” was published in 2006. A year later, Dr. Nowinski partnered with Dr. Cantu to found the Sports Legacy Institute, which eventually became the Concussion Legacy Foundation (CLF).


 

Cold calling for brain donations

Robert Stern, PhD, is another highly respected authority in the study of neurodegenerative disease. In 2007, he was directing the clinical core of Boston University’s Alzheimer’s Disease Center. After giving a lecture to a group of financial planners and elder-law attorneys one morning, he got a request for a private meeting from a fellow named Chris Nowinski.

“I’d never heard of him, but I agreed,” recalled Dr. Stern, a professor of neurology, neurosurgery, anatomy, and neurobiology at Boston University. “A few days later, this larger-than-life guy walked into our conference room at the BU School of Medicine, exuding a great deal of passion, intellect, and determination. He told me his story and then started talking about the long-term consequences of concussions in sports.”

Dr. Stern had seen patients with dementia pugilistica, the old-school term for CTE. These were mostly boxers with cognitive and behavioral impairment. “But I had not heard about football players,” he said. “I hadn’t put the two together. And as I was listening to Chris, I realized if what he was saying was true then it was not only a potentially huge public health issue, but it was also a potentially huge scientific issue in the field of neurodegenerative disease.” 

Dr. Nowinski introduced Dr. Stern to Dr. Cantu, and together with Ann McKee, MD, professor of neurology and pathology at BU, they cofounded the Center for the Study of Traumatic Encephalopathy (CSTE) in 2008. It was the first center of its kind devoted to the study of CTE in the world.

One of Dr. Nowinski’s first jobs at the CSTE was soliciting and procuring brain donations. Since CTE is generally a progressive condition that can take decades to manifest, autopsy was the only way to detect it.

The brains of two former Pittsburgh Steelers, Mike Webster and Terry Long, had been examined after their untimely deaths. After immunostaining, investigators found both former NFL players had “protein misfolds” characteristic of CTE.

This finding drew a lot of public and scientific attention, given that Mr. Long died by suicide and Mr. Webster was homeless when he died of a heart attack. But more scientific evidence was needed to prove a causal link between the head trauma and CTE.

Dr. Nowinski scoured obituaries looking for potential brains to study. When he found one, he would cold call the family and try to convince them to donate it to science. The first brain he secured for the center belonged to John Grimsley, a former NFL linebacker who in 2008 died at age 45 of an accidental gunshot wound. Often, Dr. Nowinski would even be the courier, traveling to pick up the brain after it had been harvested.

Over the next 10 years, Dr. Nowinski and his research team secured 500 brain donations. The research that resulted was staggering. In the beginning only 45 cases of CTE had been identified in the world, but in the first 111 NFL players who were autopsied, 110 had the disorder.

Of the first 53 college football players autopsied, 48 had CTE. Although Dr. Nowinski’s initial focus was football, evidence of CTE was soon detected among athletes in boxing, hockey, soccer, and rugby, as well as in combat veterans. However, the National Football League and other governing sports bodies initially denied any connection between sport-related head trauma and CTE.
 

Cumulative damage

In 2017, after 7 years of study, Dr. Nowinski earned a PhD in neurology. As the scientific evidence continued to accumulate, two shifts occurred that Dr. Stern said represent Dr. Nowinski’s greatest contributions. First, concussion is now widely recognized as an acute brain injury with symptoms that need to be immediately diagnosed and addressed.

“This is a completely different story from where things were just 10 years ago,” said Dr. Stern, “and Chris played a central role, if not the central role, in raising awareness about that.”

All 50 states and the District of Columbia now have laws regarding sports-related concussion. And there are brain banks in Australia, Canada, New Zealand, Brazil, and the United Kingdom studying CTE. More than 2,500 athletes in a variety of sports, including NASCAR’s Dale Earnhardt Jr. and NFL hall of famer Nick Buoniconti, have publicly pledged to donate their brains to science after their deaths.

Second, said Dr. Stern, we now know that although concussions can contribute to CTE, they are not the sole cause. It’s repetitive subconcussive trauma, without symptoms of concussion, that do the most damage.

“These happen during every practice and in every game,” said Dr. Stern. In fact, it’s estimated that pro football players suffer thousands of subconcussive incidents over the course of their careers. So, a player doesn’t have to see stars or lose consciousness to suffer brain damage; small impacts can accumulate over time.

Understanding this point is crucial for making youth sports safer. “Chris has played a critical role in raising awareness here, too,” said Dr. Stern. “Allowing our kids to get hit in the head over and over can put them at greater risk for later problems, plus it just doesn’t make common sense.”

“The biggest misconception surrounding head trauma in sports,” said Dr. Nowinski, “is the belief among players, coaches, and even the medical and scientific communities that if you get hit in the head and don’t have any symptoms then you’re okay and there hasn’t been any damage. That couldn’t be further from the truth. We now know that people are suffering serious brain injuries due to the accumulated effect of subconcussive impacts, and we need to get the word out about that.”

A major initiative from the Concussion Legacy Foundation called “Stop Hitting Kids in the Head” has the goal of convincing every sport to eliminate repetitive head impacts in players under age 14 – the time when the skull and brain are still developing and most vulnerable – by 2026. In fact, Dr. Nowinski wrote that “there could be a lot of kids who are misdiagnosed and medicated for various behavioral or emotional problems that may actually be head injury–related.”

Starting in 2009, the NFL adopted a series of rule changes designed to better protect its players against repeated head trauma. Among them is a ban on spearing or leading with the helmet, penalties for hitting defenseless players, and more stringent return-to-play guidelines, including concussion protocols.

The NFL has also put more emphasis on flag football options for youngsters and, for the first time, showcased this alternative in the 2023 Pro Bowl. But Dr. Nowinski is pressuring the league to go further. “While acknowledging that the game causes CTE, the NFL still underwrites recruiting 5-year-olds to play tackle football,” he said. “In my opinion, that’s unethical, and it needs to be addressed.”
 

WWE one of the most responsive organizations

Dr. Nowinski said WWE has been one of the most responsive sports organizations for protecting athletes. A doctor is now ringside at every match as is an observer who knows the script, thereby allowing for instant medical intervention if something goes wrong. “Since everyone is trying to look like they have a concussion all the time, it takes a deep understanding of the business to recognize a real one,” he said.

But this hasn’t been the case with other sports. “I am eternally disappointed in the response of the professional sports industry to the knowledge of CTE and long-term concussion symptoms,” said Dr. Nowinski.

“For example, FIFA [international soccer’s governing body] still doesn’t allow doctors to evaluate [potentially concussed] players on the sidelines and put them back in the game with a free substitution [if they’re deemed okay]. Not giving players proper medical care for a brain injury is unethical,” he said. BU’s Center for the Study of Traumatic Encephalopathy diagnosed the first CTE case in soccer in 2012, and in 2015 Dr. Nowinski successfully lobbied U.S. Soccer to ban heading the ball before age 11.

“Unfortunately, many governing bodies have circled the wagons in denying their sport causes CTE,” he continued. “FIFA, World Rugby, the NHL, even the NCAA and International Olympic Committee refuse to acknowledge it and, therefore, aren’t taking any steps to prevent it. They see it as a threat to their business model. Hopefully, now that the NIH and CDC are aligned about the risks of head impact in sports, this will begin to change.”

Meanwhile, research is continuing. Scientists are getting closer to being able to diagnose CTE in living humans, with ongoing studies using PET scans, blood markers, and spinal fluid markers. In 2019, researchers identified tau proteins specific to CTE that they believe are distinct from those of Alzheimer’s and other neurodegenerative diseases. Next step would be developing a drug to slow the development of CTE once detected.

Nonetheless, athletes at all levels in impact sports still don’t fully appreciate the risks of repeated head trauma and especially subconcussive blows. “I talk to former NFL and college players every week,” said Dr. Stern. “Some tell me, ‘I love the sport, it gave me so much, and I would do it again, but I’m not letting my grandchildren play.’ But others say, ‘As long as they know the risks, they can make their own decision.’ “

Dr. Nowinski has a daughter who is 4 and a son who’s 2. Both play soccer but, thanks to dad, heading isn’t allowed in their age groups. If they continue playing sports, Dr. Nowinski said he’ll make sure they understand the risks and how to protect themselves. This is a conversation all parents should have with their kids at every level to make sure they play safe, he added.

Those in the medical community can also volunteer their time to explain head trauma to athletes, coaches, and school administrators to be sure they understand its seriousness and are doing everything to protect players.

As you watch this year’s Super Bowl, Dr. Nowinski and his team would like you to keep something in mind. Those young men on the field for your entertainment are receiving mild brain trauma repeatedly throughout the game.

Even if it’s not a huge hit that gets replayed and makes everyone gasp, even if no one gets ushered into the little sideline tent for a concussion screening, even if no one loses consciousness, brain damage is still occurring. Watch the heads of the players during every play and think about what’s going on inside their skulls regardless of how big and strong those helmets look.

A version of this article first appeared on Medscape.com.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

Key clinical point: Increased intake of dietary fiber seemed protective against migraine or severe headache in a large population of US adults.

Major finding: Risk for migraine or severe headache was 26% lower among patients in the highest (22.10-95.50 g/day) vs lowest (0.0-7.79 g/day) quintile of dietary fiber intake (adjusted odds ratio 0.74; P  =  .0029).

Study details: This cross-sectional study included 12,710 participants from the US National Health and Nutrition Examination Survey, of which 2527 experienced migraine or severe headache.

Disclosures: This study did not declare the source of funding. The authors declared no conflicts of interest.

Source: Huang H and He K. The association between dietary fiber intake and severe headaches or migraine in US adults. Front Nutr. 2023;9:1044066  (Jan 4). Doi: 10.3389/fnut.2022.1044066

Key clinical point: Increased intake of dietary fiber seemed protective against migraine or severe headache in a large population of US adults.

Major finding: Risk for migraine or severe headache was 26% lower among patients in the highest (22.10-95.50 g/day) vs lowest (0.0-7.79 g/day) quintile of dietary fiber intake (adjusted odds ratio 0.74; P  =  .0029).

Study details: This cross-sectional study included 12,710 participants from the US National Health and Nutrition Examination Survey, of which 2527 experienced migraine or severe headache.

Disclosures: This study did not declare the source of funding. The authors declared no conflicts of interest.

Source: Huang H and He K. The association between dietary fiber intake and severe headaches or migraine in US adults. Front Nutr. 2023;9:1044066  (Jan 4). Doi: 10.3389/fnut.2022.1044066

Key clinical point: Increased intake of dietary fiber seemed protective against migraine or severe headache in a large population of US adults.

Major finding: Risk for migraine or severe headache was 26% lower among patients in the highest (22.10-95.50 g/day) vs lowest (0.0-7.79 g/day) quintile of dietary fiber intake (adjusted odds ratio 0.74; P  =  .0029).

Study details: This cross-sectional study included 12,710 participants from the US National Health and Nutrition Examination Survey, of which 2527 experienced migraine or severe headache.

Disclosures: This study did not declare the source of funding. The authors declared no conflicts of interest.

Source: Huang H and He K. The association between dietary fiber intake and severe headaches or migraine in US adults. Front Nutr. 2023;9:1044066  (Jan 4). Doi: 10.3389/fnut.2022.1044066

Key clinical point: Index vein served as a good biomarker for migraine aura with a high diagnostic specificity and sensitivity in the emergency setting in patients with acute neurological deficit.

Major finding: Prevalence of index vein was more frequent in patients with migraine aura (17%) vs those with stroke (2%)/epileptic seizure (4%) or control participants (1%; P < .001). Index vein was highly specific to migraine aura (specificity 97%; 95% CI 95%-99%), with an ability to diagnose migraine aura with 94% sensitivity (95% CI 87.4%-97.8%) and 73.5% specificity (95% CI 66.8%-79.5%) at a cut-off of 4 points.

Study details: This retrospective case-control study included 400 patients who presented to the emergency department with an acute neurological deficit, underwent brain magnetic resonance imaging, and were discharged with a diagnosis of migraine aura/ischemic stroke/epileptic seizure or none of these (control participants).

Disclosures: This study did not receive any specific funding. Two authors declared serving as part-time employees at Zynnon or as a consultant, speaker, or advisory board member for various sources.

Source: Scutelnic A et al. The “index vein” as a sign for migraine aura in the emergency setting. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/033310242211320

Key clinical point: Index vein served as a good biomarker for migraine aura with a high diagnostic specificity and sensitivity in the emergency setting in patients with acute neurological deficit.

Major finding: Prevalence of index vein was more frequent in patients with migraine aura (17%) vs those with stroke (2%)/epileptic seizure (4%) or control participants (1%; P < .001). Index vein was highly specific to migraine aura (specificity 97%; 95% CI 95%-99%), with an ability to diagnose migraine aura with 94% sensitivity (95% CI 87.4%-97.8%) and 73.5% specificity (95% CI 66.8%-79.5%) at a cut-off of 4 points.

Study details: This retrospective case-control study included 400 patients who presented to the emergency department with an acute neurological deficit, underwent brain magnetic resonance imaging, and were discharged with a diagnosis of migraine aura/ischemic stroke/epileptic seizure or none of these (control participants).

Disclosures: This study did not receive any specific funding. Two authors declared serving as part-time employees at Zynnon or as a consultant, speaker, or advisory board member for various sources.

Source: Scutelnic A et al. The “index vein” as a sign for migraine aura in the emergency setting. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/033310242211320

Key clinical point: Index vein served as a good biomarker for migraine aura with a high diagnostic specificity and sensitivity in the emergency setting in patients with acute neurological deficit.

Major finding: Prevalence of index vein was more frequent in patients with migraine aura (17%) vs those with stroke (2%)/epileptic seizure (4%) or control participants (1%; P < .001). Index vein was highly specific to migraine aura (specificity 97%; 95% CI 95%-99%), with an ability to diagnose migraine aura with 94% sensitivity (95% CI 87.4%-97.8%) and 73.5% specificity (95% CI 66.8%-79.5%) at a cut-off of 4 points.

Study details: This retrospective case-control study included 400 patients who presented to the emergency department with an acute neurological deficit, underwent brain magnetic resonance imaging, and were discharged with a diagnosis of migraine aura/ischemic stroke/epileptic seizure or none of these (control participants).

Disclosures: This study did not receive any specific funding. Two authors declared serving as part-time employees at Zynnon or as a consultant, speaker, or advisory board member for various sources.

Source: Scutelnic A et al. The “index vein” as a sign for migraine aura in the emergency setting. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/033310242211320

Key clinical point: American adults with higher dietary zinc intake were at a lower risk for migraine, demonstrating an inverse association between dietary zinc intake and migraine.

Major finding: The risk for migraine was significantly lower among participants in the highest (≥15.8 mg/day) vs lowest (≤5.9 mg/day) quintile of dietary zinc intake (adjusted odds ratio [aOR] 0.70; P  =  .029) and remained low among participants with dietary zinc intake of at least 6.0-8.4 mg/day (aOR 0.73; P  =  .004).

Study details: This cross-sectional study included 11,088 adults with or without migraine from the US National Health and Nutrition Examination Survey (1999-2004).

Disclosures: This study was supported by grants from the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Liu H et al. Dietary zinc intake and migraine in adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey 1999-2004. Headache. 2023 (Jan 1). Doi: 10.1111/head.14431

Key clinical point: American adults with higher dietary zinc intake were at a lower risk for migraine, demonstrating an inverse association between dietary zinc intake and migraine.

Major finding: The risk for migraine was significantly lower among participants in the highest (≥15.8 mg/day) vs lowest (≤5.9 mg/day) quintile of dietary zinc intake (adjusted odds ratio [aOR] 0.70; P  =  .029) and remained low among participants with dietary zinc intake of at least 6.0-8.4 mg/day (aOR 0.73; P  =  .004).

Study details: This cross-sectional study included 11,088 adults with or without migraine from the US National Health and Nutrition Examination Survey (1999-2004).

Disclosures: This study was supported by grants from the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Liu H et al. Dietary zinc intake and migraine in adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey 1999-2004. Headache. 2023 (Jan 1). Doi: 10.1111/head.14431

Key clinical point: American adults with higher dietary zinc intake were at a lower risk for migraine, demonstrating an inverse association between dietary zinc intake and migraine.

Major finding: The risk for migraine was significantly lower among participants in the highest (≥15.8 mg/day) vs lowest (≤5.9 mg/day) quintile of dietary zinc intake (adjusted odds ratio [aOR] 0.70; P  =  .029) and remained low among participants with dietary zinc intake of at least 6.0-8.4 mg/day (aOR 0.73; P  =  .004).

Study details: This cross-sectional study included 11,088 adults with or without migraine from the US National Health and Nutrition Examination Survey (1999-2004).

Disclosures: This study was supported by grants from the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Liu H et al. Dietary zinc intake and migraine in adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey 1999-2004. Headache. 2023 (Jan 1). Doi: 10.1111/head.14431

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Eptinezumab vs placebo demonstrated significantly greater and sustained improvements in patient-reported overall health, quality of life, and most bothersome symptoms in patients with migraine and 2-4 preventive treatment failures.

Major finding: At week 12, 100 and 300 mg eptinezumab vs placebo led to significantly greater improvements in EQ-5D-5L visual analog scale scores (difference from placebo [Δ] 5.1; P < .001, and Δ 7.5; P < .0001, respectively), 6-item Headache Impact Test total scores (Δ −3.8 and −5.4, respectively; both P < .0001), Migraine-Specific Quality of Life Questionnaire scores (both P < .0001), and patient-identified most bothersome symptoms (both P < .0001), with effects sustained until week 24.

Study details: Findings are from the phase 3b DELIVER trial including 890 adults with episodic/chronic migraine and 2-4 prior preventive treatment failures who were randomly assigned to receive eptinezumab (100/300 mg) or placebo.

Disclosures: The clinical trial and publication was funded by H. Lundbeck A/S. Five authors declared being employees of H. Lundbeck A/S. Three authors reported ties with various sources.

Source: Goadsby PJ et al. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures. Eur J Neurol. 2022 (Dec 30). Doi: 10.1111/ene.15670

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: Single session of onabotulinumtoxinA effectively reduced neck and migraine-related disability and pain intensity over 3 months in patients with chronic migraine.

Major finding: OnabotulinumtoxinA significantly reduced Neck Disability Index scores (median −16.5 points; P < .001) and Migraine Disability Assessment scores (median −28 points; P < .001) after 4 weeks. The neck pain intensity and migraine headache intensity reduced by almost half (both P < .001) and the median number of monthly headache days reduced from 20 to 6 days (P < .001) after 3 months of onabotulinumtoxinA treatment.

Study details: This retrospective study included 134 patients with chronic migraine who received one session of onabotulinumtoxinA treatment.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Onan D et al. OnabotulinumtoxinA treatment in chronic migraine: Investigation of its effects on disability, headache and neck pain intensity. Toxins (Basel). 2022;15(1):29 (Dec 30). Doi: 10.3390/toxins15010029

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: The safety and tolerability of once-daily atogepant observed over 40 weeks in this extension trial aligns with profiles from the pivotal phase 3 trials with no new safety signals identified in patients with episodic migraine.

Major finding: Nearly 63% of patients reported treatment-emergent adverse events, most being mild or moderate, with upper respiratory tract infection (5.5%) and urinary tract infection (5.3%) being most frequent. Treatment discontinuation rates due to lack of efficacy (0.6%) or adverse events (3.6%) were low. No deaths were reported.

Study details: Findings are from the 309-OLEX trial, an open-label extension of phase 3 ADVANCE trial, including 685 patients with episodic migraine with or without aura who received 60 mg atogepant once daily for 40 weeks.

Disclosures: This study was supported by AbbVie Inc. (formerly Allergan). Five authors declared being full-time or former employees of or holding stock or stock options in AbbVie. Several authors reported ties with various sources, including AbbVie.

Source: Klein BC et al. Safety and tolerability results of atogepant for the preventive treatment of episodic migraine from a 40-week, open-label multicenter extension of the phase 3 ADVANCE trial. Cephalalgia. 2023 (Jan 9). Doi: 10.1177/03331024221128250

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A preconception history of migraine showed no significant association with the risk for spontaneous abortion (SAB); however, routine use of medication, suggesting more severe migraine, may confer a greater SAB risk.

Major finding: Preconception migraine history did not increase the risk for SAB (adjusted hazard ratio [aHR] 1.03; 95% CI 0.91-1.16), but daily migraine medication use (aHR 1.38; 95% CI 0.81-2.35), use of prescription migraine prophylaxis medication (aHR 1.43; 95% CI 0.72-2.84), or analgesic/caffeine medication use (aHR 1.42; 95% CI 0.99-2.04) showed a modest but non-significant association with SAB risk.

Study details: This study evaluated 7890 participants from an ongoing prospective study who conceived during follow-up and had or did not have a preconception diagnosis of migraine or migraine medication use, of which 1537 experienced SAB.

Disclosures: This study was funded by the National Institute of Child Health and Human Development, US National Institutes of Health. The authors declared no conflicts of interest.

Source: Crowe HM et al. Pre‑pregnancy migraine diagnosis, medication use, and spontaneous abortion: A prospective cohort study. J Headache Pain. 2022;23:162 (Dec 20). Doi: 10.1186/s10194-022-01533-6

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518

Key clinical point: A brief group education and supportive self-management program had no beneficial effects on clinically relevant outcomes in patients with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache.

Major finding: At 12 months, Headache Impact Test scores (adjusted mean difference [AMD] −0.3; P  =  .56), number of headache days (AMD 0.2; P  =  .234), duration of headache (estimated difference [ED] 0.4; P  =  .361), and headache severity (ED 0.2; P  =  .163) were not significantly different between patients who received self-management intervention vs usual care.

Study details: The data come from CHESS, a randomized controlled trial, including 727 participants with chronic migraine or chronic tension type headache and episodic migraine, with or without medication overuse headache, who received self-management intervention or usual care.

Disclosures: This study was funded by the UK National Institute for Health Research Programme Grants for Applied Research program. Several authors reported receiving grants, personal fees, or honoraria from various sources or owning patent.

Source: Underwood M et al. A supportive self-management program for people with chronic headaches and migraine: A randomized controlled trial and economic evaluation. Neurology. 2022 (Dec 16). Doi: 10.1212/WNL.0000000000201518