Neurology Reviews

At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.

For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.

Doug Menuez/thinkstock

Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.

Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.

“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.

To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.

“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”

Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.

“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”

Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.

The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.

Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.

“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.

She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”

Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.

Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.

The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.

“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
 

Genetic risk factors?

One mystery is why some regular marijuana users get this syndrome while others do not.

“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”

Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.

They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.

The results are not final but could help guide future research, Dr. Russo said.

“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.

Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.

“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
 

Battling disbelief

Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.

“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.

“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.

Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.

Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.

“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.

People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.

Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.

“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.

Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
 

What recent research reveals

Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.

So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.

Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.

An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.

Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.

“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.

Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.

The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
 

Cannabis conspiracy theories

“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.

Some “myth busting” is in order, he said.

For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
 

The state of recreational and medical marijuana

Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.

One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.

“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.

In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.

Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.

“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.

Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”

“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.

“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”

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

At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.

For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.

Doug Menuez/thinkstock

Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.

Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.

“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.

To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.

“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”

Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.

“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”

Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.

The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.

Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.

“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.

She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”

Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.

Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.

The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.

“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
 

Genetic risk factors?

One mystery is why some regular marijuana users get this syndrome while others do not.

“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”

Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.

They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.

The results are not final but could help guide future research, Dr. Russo said.

“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.

Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.

“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
 

Battling disbelief

Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.

“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.

“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.

Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.

Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.

“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.

People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.

Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.

“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.

Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
 

What recent research reveals

Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.

So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.

Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.

An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.

Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.

“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.

Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.

The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
 

Cannabis conspiracy theories

“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.

Some “myth busting” is in order, he said.

For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
 

The state of recreational and medical marijuana

Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.

One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.

“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.

In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.

Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.

“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.

Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”

“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.

“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”

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

At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.

For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.

Doug Menuez/thinkstock

Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.

Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.

“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.

To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.

“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”

Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.

“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”

Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.

The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.

Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.

“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.

She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”

Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.

Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.

The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.

“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
 

Genetic risk factors?

One mystery is why some regular marijuana users get this syndrome while others do not.

“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”

Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.

They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.

The results are not final but could help guide future research, Dr. Russo said.

“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.

Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.

“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
 

Battling disbelief

Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.

“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.

“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.

Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.

Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.

“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.

People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.

Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.

“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.

Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
 

What recent research reveals

Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.

So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.

Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.

An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.

Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.

“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.

Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.

The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
 

Cannabis conspiracy theories

“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.

Some “myth busting” is in order, he said.

For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
 

The state of recreational and medical marijuana

Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.

One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.

“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.

In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.

Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.

“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.

Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”

“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.

“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”

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

Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.

Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com

Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.

Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com

Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.

Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com

It is a tough time to be a doctor. With the stresses of the pandemic, the continued unfettered rise of insurance company BS, and so many medical groups being bought up that we often don’t even know who makes the decisions, the patient can sometimes be hidden in the equation.

What are ways that we can connect well with our patients so that both the patient and the physician are lifted up by the relationship?

Be curious

When physicians are curious about why patients have symptoms, how those symptoms will affect their lives, and how worried the patient is about them, patients feel cared about.

Ascertaining how concerned patients are about their symptoms will help you make decisions on whether symptoms you are not concerned about actually need to be treated.
 

Limit use of EHRs when possible

Use of the electronic health record during visits is essential, but focusing on it too much can put a barrier between the physician and the patient.

Marmor and colleagues found there is an inverse relationship between time spent on the EHR by a patient’s physician and the patient’s satisfaction.¹

Eye contact with the patient is important, especially when patients are sharing concerns they are scared about and upsetting experiences. There can be awkward pauses when looking things up on the EHR. Fill those pauses by explaining to the patient what you are doing, or chatting with the patient.
 

Consider teaching medical students

When a medical student works with you, it doubles the time the patient gets with a concerned listener. Students also can do a great job with timely follow-up and checking in with worried patients.

By having the student present in the clinic room, with the patient present, the patient can really feel heard. The student shares all the details the patient shared, and now their physician is hearing an organized, thoughtful report of the patients concerns.

In fact, I was involved in a study that showed that patients preferred in room presentations, and that they were more satisfied when students presented in the room.²
 

Use healing words

Some words carry loaded emotions. The word chronic, for example, has negative connotations, whereas the term persisting does not.

I will often ask patients how long they have been suffering from a symptom to imply my concern for what they are going through. The term “chief complaint” is outdated, and upsets patients when they see it in their medical record.

As a patient of mine once said to me: “I never complained about that problem, I just brought it to your attention.” No one wants to be seen as a complainer. Substituting the word concern for complaint works well.
 

Explain as you examine

People love to hear the term normal. When you are examining a patient, let them know when findings are normal.

I also find it helpful to explain to patients why I am doing certain physical exam maneuvers. This helps them assess how thorough we are in our thought process.

When patients feel their physicians are thorough, they have more confidence in them.
 

In summary

• Be curious.
• Do not overly focus on the EHR.
• Consider teaching a medical student.
• Be careful of word choice.
• “Overexplain” the physical exam.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Marmor RA et al. Appl Clin Inform. 2018 Jan;9(1):11-4.

2. Rogers HD et al. Acad Med. 2003 Sep;78(9):945-9.

It is a tough time to be a doctor. With the stresses of the pandemic, the continued unfettered rise of insurance company BS, and so many medical groups being bought up that we often don’t even know who makes the decisions, the patient can sometimes be hidden in the equation.

What are ways that we can connect well with our patients so that both the patient and the physician are lifted up by the relationship?

Be curious

When physicians are curious about why patients have symptoms, how those symptoms will affect their lives, and how worried the patient is about them, patients feel cared about.

Ascertaining how concerned patients are about their symptoms will help you make decisions on whether symptoms you are not concerned about actually need to be treated.
 

Limit use of EHRs when possible

Use of the electronic health record during visits is essential, but focusing on it too much can put a barrier between the physician and the patient.

Marmor and colleagues found there is an inverse relationship between time spent on the EHR by a patient’s physician and the patient’s satisfaction.¹

Eye contact with the patient is important, especially when patients are sharing concerns they are scared about and upsetting experiences. There can be awkward pauses when looking things up on the EHR. Fill those pauses by explaining to the patient what you are doing, or chatting with the patient.
 

Consider teaching medical students

When a medical student works with you, it doubles the time the patient gets with a concerned listener. Students also can do a great job with timely follow-up and checking in with worried patients.

By having the student present in the clinic room, with the patient present, the patient can really feel heard. The student shares all the details the patient shared, and now their physician is hearing an organized, thoughtful report of the patients concerns.

In fact, I was involved in a study that showed that patients preferred in room presentations, and that they were more satisfied when students presented in the room.²
 

Use healing words

Some words carry loaded emotions. The word chronic, for example, has negative connotations, whereas the term persisting does not.

I will often ask patients how long they have been suffering from a symptom to imply my concern for what they are going through. The term “chief complaint” is outdated, and upsets patients when they see it in their medical record.

As a patient of mine once said to me: “I never complained about that problem, I just brought it to your attention.” No one wants to be seen as a complainer. Substituting the word concern for complaint works well.
 

Explain as you examine

People love to hear the term normal. When you are examining a patient, let them know when findings are normal.

I also find it helpful to explain to patients why I am doing certain physical exam maneuvers. This helps them assess how thorough we are in our thought process.

When patients feel their physicians are thorough, they have more confidence in them.
 

In summary

• Be curious.
• Do not overly focus on the EHR.
• Consider teaching a medical student.
• Be careful of word choice.
• “Overexplain” the physical exam.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Marmor RA et al. Appl Clin Inform. 2018 Jan;9(1):11-4.

2. Rogers HD et al. Acad Med. 2003 Sep;78(9):945-9.

It is a tough time to be a doctor. With the stresses of the pandemic, the continued unfettered rise of insurance company BS, and so many medical groups being bought up that we often don’t even know who makes the decisions, the patient can sometimes be hidden in the equation.

What are ways that we can connect well with our patients so that both the patient and the physician are lifted up by the relationship?

Be curious

When physicians are curious about why patients have symptoms, how those symptoms will affect their lives, and how worried the patient is about them, patients feel cared about.

Ascertaining how concerned patients are about their symptoms will help you make decisions on whether symptoms you are not concerned about actually need to be treated.
 

Limit use of EHRs when possible

Use of the electronic health record during visits is essential, but focusing on it too much can put a barrier between the physician and the patient.

Marmor and colleagues found there is an inverse relationship between time spent on the EHR by a patient’s physician and the patient’s satisfaction.¹

Eye contact with the patient is important, especially when patients are sharing concerns they are scared about and upsetting experiences. There can be awkward pauses when looking things up on the EHR. Fill those pauses by explaining to the patient what you are doing, or chatting with the patient.
 

Consider teaching medical students

When a medical student works with you, it doubles the time the patient gets with a concerned listener. Students also can do a great job with timely follow-up and checking in with worried patients.

By having the student present in the clinic room, with the patient present, the patient can really feel heard. The student shares all the details the patient shared, and now their physician is hearing an organized, thoughtful report of the patients concerns.

In fact, I was involved in a study that showed that patients preferred in room presentations, and that they were more satisfied when students presented in the room.²
 

Use healing words

Some words carry loaded emotions. The word chronic, for example, has negative connotations, whereas the term persisting does not.

I will often ask patients how long they have been suffering from a symptom to imply my concern for what they are going through. The term “chief complaint” is outdated, and upsets patients when they see it in their medical record.

As a patient of mine once said to me: “I never complained about that problem, I just brought it to your attention.” No one wants to be seen as a complainer. Substituting the word concern for complaint works well.
 

Explain as you examine

People love to hear the term normal. When you are examining a patient, let them know when findings are normal.

I also find it helpful to explain to patients why I am doing certain physical exam maneuvers. This helps them assess how thorough we are in our thought process.

When patients feel their physicians are thorough, they have more confidence in them.
 

In summary

• Be curious.
• Do not overly focus on the EHR.
• Consider teaching a medical student.
• Be careful of word choice.
• “Overexplain” the physical exam.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Marmor RA et al. Appl Clin Inform. 2018 Jan;9(1):11-4.

2. Rogers HD et al. Acad Med. 2003 Sep;78(9):945-9.

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Several long COVID symptoms could be linked to the effects of the coronavirus on a vital central nerve, according to new research being released in the spring.

The vagus nerve, which runs from the brain into the body, connects to the heart, lungs, intestines, and several muscles involved with swallowing. It plays a role in several body functions that control heart rate, speech, the gag reflex, sweating, and digestion.

Those with long COVID and vagus nerve problems could face long-term issues with their voice, a hard time swallowing, dizziness, a high heart rate, low blood pressure, and diarrhea, the study authors found.

Their findings will be presented at the 2022 European Congress of Clinical Microbiology and Infectious Diseases in late April.

“Most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing,” the study authors wrote. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”

Researchers from the University Hospital Germans Trias i Pujol in Barcelona performed a study to look at vagus nerve functioning in long COVID patients. Among 348 patients, about 66% had at least one symptom that suggested vagus nerve dysfunction. The researchers did a broad evaluation with imaging and functional tests for 22 patients in the university’s Long COVID Clinic from March to June 2021.

Of the 22 patients, 20 were women, and the median age was 44. The most frequent symptoms related to vagus nerve dysfunction were diarrhea (73%), high heart rates (59%), dizziness (45%), swallowing problems (45%), voice problems (45%), and low blood pressure (14%).

Almost all (19 of 22 patients) had three or more symptoms related to vagus nerve dysfunction. The average length of symptoms was 14 months.

Of 22 patients, 6 had a change in the vagus nerve in the neck, which the researchers observed by ultrasound. They had a thickening of the vagus nerve and increased “echogenicity,” which suggests inflammation.

What’s more, 10 of 22 patients had flattened “diaphragmatic curves” during a thoracic ultrasound, which means the diaphragm doesn’t move as well as it should during breathing, and abnormal breathing. In another assessment, 10 of 16 patients had lower maximum inspiration pressures, suggesting a weakness in breathing muscles.

Eating and digestion were also impaired in some patients, with 13 reporting trouble with swallowing. During a gastric and bowel function assessment, eight patients couldn’t move food from the esophagus to the stomach as well as they should, while nine patients had acid reflux. Three patients had a hiatal hernia, which happens when the upper part of the stomach bulges through the diaphragm into the chest cavity.

The voices of some patients changed as well. Eight patients had an abnormal voice handicap index 30 test, which is a standard way to measure voice function. Among those, seven patients had dysphonia, or persistent voice problems.

The study is ongoing, and the research team is continuing to recruit patients to study the links between long COVID and the vagus nerve. The full paper isn’t yet available, and the research hasn’t yet been peer reviewed.

“The study appears to add to a growing collection of data suggesting at least some of the symptoms of long COVID is mediated through a direct impact on the nervous system,” David Strain, MD, a clinical senior lecturer at the University of Exeter (England), told the Science Media Centre.

“Establishing vagal nerve damage is useful information, as there are recognized, albeit not perfect, treatments for other causes of vagal nerve dysfunction that may be extrapolated to be beneficial for people with this type of long COVID,” he said.

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

Several long COVID symptoms could be linked to the effects of the coronavirus on a vital central nerve, according to new research being released in the spring.

The vagus nerve, which runs from the brain into the body, connects to the heart, lungs, intestines, and several muscles involved with swallowing. It plays a role in several body functions that control heart rate, speech, the gag reflex, sweating, and digestion.

Those with long COVID and vagus nerve problems could face long-term issues with their voice, a hard time swallowing, dizziness, a high heart rate, low blood pressure, and diarrhea, the study authors found.

Their findings will be presented at the 2022 European Congress of Clinical Microbiology and Infectious Diseases in late April.

“Most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing,” the study authors wrote. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”

Researchers from the University Hospital Germans Trias i Pujol in Barcelona performed a study to look at vagus nerve functioning in long COVID patients. Among 348 patients, about 66% had at least one symptom that suggested vagus nerve dysfunction. The researchers did a broad evaluation with imaging and functional tests for 22 patients in the university’s Long COVID Clinic from March to June 2021.

Of the 22 patients, 20 were women, and the median age was 44. The most frequent symptoms related to vagus nerve dysfunction were diarrhea (73%), high heart rates (59%), dizziness (45%), swallowing problems (45%), voice problems (45%), and low blood pressure (14%).

Almost all (19 of 22 patients) had three or more symptoms related to vagus nerve dysfunction. The average length of symptoms was 14 months.

Of 22 patients, 6 had a change in the vagus nerve in the neck, which the researchers observed by ultrasound. They had a thickening of the vagus nerve and increased “echogenicity,” which suggests inflammation.

What’s more, 10 of 22 patients had flattened “diaphragmatic curves” during a thoracic ultrasound, which means the diaphragm doesn’t move as well as it should during breathing, and abnormal breathing. In another assessment, 10 of 16 patients had lower maximum inspiration pressures, suggesting a weakness in breathing muscles.

Eating and digestion were also impaired in some patients, with 13 reporting trouble with swallowing. During a gastric and bowel function assessment, eight patients couldn’t move food from the esophagus to the stomach as well as they should, while nine patients had acid reflux. Three patients had a hiatal hernia, which happens when the upper part of the stomach bulges through the diaphragm into the chest cavity.

The voices of some patients changed as well. Eight patients had an abnormal voice handicap index 30 test, which is a standard way to measure voice function. Among those, seven patients had dysphonia, or persistent voice problems.

The study is ongoing, and the research team is continuing to recruit patients to study the links between long COVID and the vagus nerve. The full paper isn’t yet available, and the research hasn’t yet been peer reviewed.

“The study appears to add to a growing collection of data suggesting at least some of the symptoms of long COVID is mediated through a direct impact on the nervous system,” David Strain, MD, a clinical senior lecturer at the University of Exeter (England), told the Science Media Centre.

“Establishing vagal nerve damage is useful information, as there are recognized, albeit not perfect, treatments for other causes of vagal nerve dysfunction that may be extrapolated to be beneficial for people with this type of long COVID,” he said.

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

Several long COVID symptoms could be linked to the effects of the coronavirus on a vital central nerve, according to new research being released in the spring.

The vagus nerve, which runs from the brain into the body, connects to the heart, lungs, intestines, and several muscles involved with swallowing. It plays a role in several body functions that control heart rate, speech, the gag reflex, sweating, and digestion.

Those with long COVID and vagus nerve problems could face long-term issues with their voice, a hard time swallowing, dizziness, a high heart rate, low blood pressure, and diarrhea, the study authors found.

Their findings will be presented at the 2022 European Congress of Clinical Microbiology and Infectious Diseases in late April.

“Most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing,” the study authors wrote. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”

Researchers from the University Hospital Germans Trias i Pujol in Barcelona performed a study to look at vagus nerve functioning in long COVID patients. Among 348 patients, about 66% had at least one symptom that suggested vagus nerve dysfunction. The researchers did a broad evaluation with imaging and functional tests for 22 patients in the university’s Long COVID Clinic from March to June 2021.

Of the 22 patients, 20 were women, and the median age was 44. The most frequent symptoms related to vagus nerve dysfunction were diarrhea (73%), high heart rates (59%), dizziness (45%), swallowing problems (45%), voice problems (45%), and low blood pressure (14%).

Almost all (19 of 22 patients) had three or more symptoms related to vagus nerve dysfunction. The average length of symptoms was 14 months.

Of 22 patients, 6 had a change in the vagus nerve in the neck, which the researchers observed by ultrasound. They had a thickening of the vagus nerve and increased “echogenicity,” which suggests inflammation.

What’s more, 10 of 22 patients had flattened “diaphragmatic curves” during a thoracic ultrasound, which means the diaphragm doesn’t move as well as it should during breathing, and abnormal breathing. In another assessment, 10 of 16 patients had lower maximum inspiration pressures, suggesting a weakness in breathing muscles.

Eating and digestion were also impaired in some patients, with 13 reporting trouble with swallowing. During a gastric and bowel function assessment, eight patients couldn’t move food from the esophagus to the stomach as well as they should, while nine patients had acid reflux. Three patients had a hiatal hernia, which happens when the upper part of the stomach bulges through the diaphragm into the chest cavity.

The voices of some patients changed as well. Eight patients had an abnormal voice handicap index 30 test, which is a standard way to measure voice function. Among those, seven patients had dysphonia, or persistent voice problems.

The study is ongoing, and the research team is continuing to recruit patients to study the links between long COVID and the vagus nerve. The full paper isn’t yet available, and the research hasn’t yet been peer reviewed.

“The study appears to add to a growing collection of data suggesting at least some of the symptoms of long COVID is mediated through a direct impact on the nervous system,” David Strain, MD, a clinical senior lecturer at the University of Exeter (England), told the Science Media Centre.

“Establishing vagal nerve damage is useful information, as there are recognized, albeit not perfect, treatments for other causes of vagal nerve dysfunction that may be extrapolated to be beneficial for people with this type of long COVID,” he said.

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

The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.

The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.

Both groups had a much lower event rate compared with a historical control group made up of similar patients.

In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.  

“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.

“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”

Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.

“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.  

Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.

“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.

Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.

For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.

Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.

The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.

All patients received comprehensive conventional stroke risk factor treatment.

The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.   

Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).

But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.

In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.

Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.

Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.

A new part of routine post-stroke care?

“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.

He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”

Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.

“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”

“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.  

But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.

“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
 

‘Promising’ results

Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.

“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”

The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).

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

The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.

The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.

Both groups had a much lower event rate compared with a historical control group made up of similar patients.

In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.  

“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.

“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”

Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.

“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.  

Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.

“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.

Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.

For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.

Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.

The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.

All patients received comprehensive conventional stroke risk factor treatment.

The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.   

Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).

But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.

In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.

Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.

Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.

A new part of routine post-stroke care?

“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.

He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”

Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.

“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”

“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.  

But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.

“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
 

‘Promising’ results

Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.

“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”

The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).

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

The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.

The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.

Both groups had a much lower event rate compared with a historical control group made up of similar patients.

In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.  

“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.

“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”

Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.

“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.  

Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.

“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.

Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.

For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.

Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.

The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.

All patients received comprehensive conventional stroke risk factor treatment.

The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.   

Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).

But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.

In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.

Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.

Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.

A new part of routine post-stroke care?

“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.

He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”

Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.

“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”

“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.  

But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.

“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
 

‘Promising’ results

Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.

“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”

The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).

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

Patients with an ischemic stroke treated with tenecteplase have almost a 50% lower rate of symptomatic intracranial hemorrhage compared with those receiving alteplase, preliminary results from a large, multicenter registry study suggest.

“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.

“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.

The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.

Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”

Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”

However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.

Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.

The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.

Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).

Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.

They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.

Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”

In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).

Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”

An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)

The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.

“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.

He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”

Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.

Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.

“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.

Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”

Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.

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

Patients with an ischemic stroke treated with tenecteplase have almost a 50% lower rate of symptomatic intracranial hemorrhage compared with those receiving alteplase, preliminary results from a large, multicenter registry study suggest.

“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.

“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.

The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.

Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”

Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”

However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.

Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.

The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.

Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).

Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.

They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.

Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”

In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).

Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”

An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)

The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.

“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.

He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”

Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.

Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.

“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.

Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”

Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.

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

Patients with an ischemic stroke treated with tenecteplase have almost a 50% lower rate of symptomatic intracranial hemorrhage compared with those receiving alteplase, preliminary results from a large, multicenter registry study suggest.

“In clinical practice where centers are using tenecteplase, we’re seeing that the rate of symptomatic hemorrhage after getting a thrombolytic is half that with tenecteplase than with alteplase,” said lead author Steven J. Warach, MD, PhD, professor of neurology at Dell Medical School, University of Texas, Austin.

“For clinicians who have switched or are considering switching to tenecteplase, I think these results are very reassuring,” he said at the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Tenecteplase is a relatively new agent that is approved by the U.S. Food and Drug Administration to treat myocardial infarction but not ischemic stroke, although clinicians sometimes use it off-label for this purpose. American Heart Association guidelines recommend tenecteplase might be reasonable to consider for ischemic stroke in select patients.

The current standard of care for stroke is alteplase, which has been approved for this indication since 1996.

Five randomized clinical trials comparing the two thrombolytics weren’t large enough to make definitive conclusions about differences, said Dr. Warach. “The event rate for serious bleeding into the brain was thankfully low in both groups.”

Results from a meta-analysis that combined data from those five trials were also not definitive. “Numerically, it looked like the rate was lower for tenecteplase, but the sample size was just too low to make any statistically confident statement.”

However, tenecteplase has practical advantages over alteplase. Tenecteplase is a single bolus injection lasting 5 seconds while alteplase is administered by injection followed by an hour-long infusion.

Given these potential advantages, some centers have changed their practice and started using the newer drug beginning in July 2018.

The current study used an ongoing large registry to compare rates of symptomatic intracranial hemorrhage in patients treated with either of these drugs. The registry includes data collected July 2018 to June 2021 from various hospitals and programs in New Zealand, Australia, and the U.S.

Symptomatic intracranial hemorrhage was defined as a severe bleed causing pressure on the brain, extensive swelling, and worsening by at least four points on the National Institutes of Health Stroke Scale (NIHSS).

Researchers abstracted data from the various registries. As not all centers record data in the same format, statisticians then “cleaned” or harmonized the data to make it more standardized, said Dr. Warach.

They controlled for factors known to put a patient at higher risk for symptomatic hemorrhage, including age, sex, baseline NIHSS, and time to treatment.

Dr. Warach noted that at baseline, the tenecteplase group had higher values on most of these factors “that would predict intracranial hemorrhage.”

In an earlier analysis of 7,891 patients, the tenecteplase group was older (73 vs. 70 years; P < .001), less likely to be female (44.1% vs. 48.7%; P = .001), and had higher NIHSS scores (9 vs. 7; P < .001).

Also, a greater percentage of those in the tenecteplase group underwent mechanical thrombectomy (36.7% vs. 18.0%; P < .001). Dr. Warach explained that some centers would opt for tenecteplase if they knew the patient was a candidate for thrombectomy “because that was where the data was clearly strong and positive.”

An updated analysis included 9,238 patients – 7,313 who received alteplase and 1,925 tenecteplase. In the updated unadjusted analysis, the symptomatic intracranial hemorrhage rate was 3.6% for alteplase and 1.8% for tenecteplase (odds ratio, 0.49; P < .001). The adjusted OR was 0.42 (P < .001.)

The difference was even greater in those who underwent thrombectomy. For patients undergoing this procedure after a thrombolytic, the symptomatic intracranial hemorrhage rate was 5.9% for alteplase and 2.4% for tenecteplase.

“That even in those higher-risk patients we’re seeing an even greater difference is promising,” said Dr. Warach.

He and his colleagues plan to assess other potential benefits of tenecteplase, for example, the time it takes for patients to recover, “once we have all the data standardized and cleaned.”

Results of three large phase 3 trials comparing the two thrombolytics are expected within the next year or two, said Dr. Warach.

Joseph Broderick, MD, professor and director of the UC Gardner Neuroscience Institute, director of the National Coordinating Center for NIH’s StrokeNet, and professor of medicine at the University of Cincinnati College of Medicine, Cincinnati, stressed that for both drugs, speed is of the utmost importance to protect the brain.

“No matter which of these drugs is going to be used, the key thing is that they have to be used as quickly as possible,” he said.

Also important is imaging the brain before administering either of these medications to ensure the issue is an ischemic stroke and not an intracerebral hemorrhage, said Dr. Broderick. “If you have a broken blood vessel, you want to seal the leak, not break up the clot and make the bleeding worse.”

Dr. Warach receives payment as chair of the safety committee of another Genentech study comparing tenecteplase versus placebo in patients with large vessel occlusion whose stroke began more than 4.5 hours before treatment.

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

Giving intra-arterial thrombolysis after successful thrombectomy in patients with acute ischemic stroke led to a large increase in the number of patients achieving an excellent neurologic outcome at 90 days in a new study.

The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.

The study was also published online in JAMA to coincide with the presentation at the ISC.

The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.   

This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”

He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.

The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
 

‘Dramatic and exciting results’

The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”

“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”

And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”

Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”

But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
 

An abbreviated phase 2b trial

The CHOICE trial was conducted in seven centers in Catalonia, Spain.

For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.

Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.

Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).

The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).   

Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).

The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.

He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.

In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.

“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.

Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.

In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”

However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.

But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”

Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.

Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.

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

Giving intra-arterial thrombolysis after successful thrombectomy in patients with acute ischemic stroke led to a large increase in the number of patients achieving an excellent neurologic outcome at 90 days in a new study.

The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.

The study was also published online in JAMA to coincide with the presentation at the ISC.

The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.   

This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”

He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.

The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
 

‘Dramatic and exciting results’

The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”

“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”

And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”

Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”

But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
 

An abbreviated phase 2b trial

The CHOICE trial was conducted in seven centers in Catalonia, Spain.

For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.

Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.

Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).

The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).   

Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).

The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.

He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.

In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.

“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.

Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.

In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”

However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.

But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”

Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.

Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.

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

Giving intra-arterial thrombolysis after successful thrombectomy in patients with acute ischemic stroke led to a large increase in the number of patients achieving an excellent neurologic outcome at 90 days in a new study.

The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.

The study was also published online in JAMA to coincide with the presentation at the ISC.

The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.   

This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”

He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.

The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
 

‘Dramatic and exciting results’

The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”

“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”

And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”

Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”

But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
 

An abbreviated phase 2b trial

The CHOICE trial was conducted in seven centers in Catalonia, Spain.

For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.

Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.

Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).

The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).   

Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).

The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.

He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.

In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.

“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.

Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.

In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”

However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.

But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”

Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.

Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

The International League Against Epilepsy (ILAE) has issued recommendations for treating depression in patients with epilepsy.

The new guidance highlights the high prevalence of depression among patients with epilepsy while offering the first systematic approach to treatment, reported lead author Marco Mula, MD, PhD, of Atkinson Morley Regional Neuroscience Centre at St George’s University Hospital, London, and colleagues.

“Despite evidence that depression represents a frequently encountered comorbidity [among patients with epilepsy], data on the treatment of depression in epilepsy [are] still limited and recommendations rely mostly on individual clinical experience and expertise,” the investigators wrote in Epilepsia.

Recommendations cover first-line treatment of unipolar depression in epilepsy without other psychiatric disorders.

For patients with mild depression, the guidance supports psychological intervention without pharmacologic therapy; however, if the patient wishes to use medication, has had a positive response to medication in the past, or nonpharmacologic treatments have previously failed or are unavailable, then SSRIs should be considered first-choice therapy. For moderate to severe depression, SSRIs are the first choice, according to Dr. Mula and colleagues.

“It has to be acknowledged that there is considerable debate in the psychiatric literature about the treatment of mild depression in adults,” the investigators noted. “A patient-level meta-analysis pointed out that the magnitude of benefit of antidepressant medications compared with placebo increases with severity of depression symptoms and it may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.”

If a patient does not respond to first-line therapy, then venlafaxine should be considered, according to the guidance. When a patient does respond to therapy, treatment should be continued for at least 6 months, and when residual symptoms persist, treatment should be continued until resolution.

“In people with depression it is established that around two-thirds of patients do not achieve full remission with first-line treatment,” Dr. Mula and colleagues wrote. “In people with epilepsy, current data show that up to 50% of patients do not achieve full remission from depression. For this reason, augmentation strategies are often needed. They should be adopted by psychiatrists, neuropsychiatrists, or mental health professionals familiar with such therapeutic strategies.”

Beyond these key recommendations, the guidance covers a range of additional topics, including other pharmacologic options, medication discontinuation strategies, electroconvulsive therapy, light therapy, exercise training, vagus nerve stimulation, and repetitive transcranial magnetic stimulation.
 

Useful advice that counters common misconceptions

According to Jacqueline A. French, MD, a professor at NYU Langone Medical Center, Dr. Mula and colleagues are “top notch,” and their recommendations “hit every nail on the head.”

Dr. French, chief medical officer of The Epilepsy Foundation, emphasized the importance of the publication, which addresses two common misconceptions within the medical community: First, that standard antidepressants are insufficient to treat depression in patients with epilepsy, and second, that antidepressants may trigger seizures.

“The first purpose [of the publication] is to say, yes, these antidepressants do work,” Dr. French said, “and no, they don’t worsen seizures, and you can use them safely, and they are appropriate to use.”

Dr. French explained that managing depression remains a practice gap among epileptologists and neurologists because it is a diagnosis that doesn’t traditionally fall into their purview, yet many patients with epilepsy forgo visiting their primary care providers, who more frequently diagnose and manage depression. Dr. French agreed with the guidance that epilepsy specialists should fill this gap.

“We need to at least be able to take people through their first antidepressant, even though we were not trained to be psychiatrists,” Dr. French said. “That’s part of the best care of our patients.”

Imad Najm, MD, director of the Charles Shor Epilepsy Center, Cleveland Clinic, said the recommendations are a step forward in the field, as they are supported by clinical data, instead of just clinical experience and expertise.

Still, Dr. Najm noted that more work is needed to stratify risk of depression in epilepsy and evaluate a possible causal relationship between epilepsy therapies and depression.

He went on to emphasizes the scale of issue at hand, and the stakes involved.

“Depression, anxiety, and psychosis affect a large number of patients with epilepsy,” Dr. Najm said. “Clinical screening and recognition of these comorbidities leads to the institution of treatment options and significant improvement in quality of life. Mental health professionals should be an integral part of any comprehensive epilepsy center.”

The investigators disclosed relationships with Esai, UCB, Elsevier, and others. Dr. French is indirectly involved with multiple pharmaceutical companies developing epilepsy drugs through her role as director of The Epilepsy Study Consortium, a nonprofit organization. Dr. Najm reported no conflicts of interest.

The International League Against Epilepsy (ILAE) has issued recommendations for treating depression in patients with epilepsy.

The new guidance highlights the high prevalence of depression among patients with epilepsy while offering the first systematic approach to treatment, reported lead author Marco Mula, MD, PhD, of Atkinson Morley Regional Neuroscience Centre at St George’s University Hospital, London, and colleagues.

“Despite evidence that depression represents a frequently encountered comorbidity [among patients with epilepsy], data on the treatment of depression in epilepsy [are] still limited and recommendations rely mostly on individual clinical experience and expertise,” the investigators wrote in Epilepsia.

Recommendations cover first-line treatment of unipolar depression in epilepsy without other psychiatric disorders.

For patients with mild depression, the guidance supports psychological intervention without pharmacologic therapy; however, if the patient wishes to use medication, has had a positive response to medication in the past, or nonpharmacologic treatments have previously failed or are unavailable, then SSRIs should be considered first-choice therapy. For moderate to severe depression, SSRIs are the first choice, according to Dr. Mula and colleagues.

“It has to be acknowledged that there is considerable debate in the psychiatric literature about the treatment of mild depression in adults,” the investigators noted. “A patient-level meta-analysis pointed out that the magnitude of benefit of antidepressant medications compared with placebo increases with severity of depression symptoms and it may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.”

If a patient does not respond to first-line therapy, then venlafaxine should be considered, according to the guidance. When a patient does respond to therapy, treatment should be continued for at least 6 months, and when residual symptoms persist, treatment should be continued until resolution.

“In people with depression it is established that around two-thirds of patients do not achieve full remission with first-line treatment,” Dr. Mula and colleagues wrote. “In people with epilepsy, current data show that up to 50% of patients do not achieve full remission from depression. For this reason, augmentation strategies are often needed. They should be adopted by psychiatrists, neuropsychiatrists, or mental health professionals familiar with such therapeutic strategies.”

Beyond these key recommendations, the guidance covers a range of additional topics, including other pharmacologic options, medication discontinuation strategies, electroconvulsive therapy, light therapy, exercise training, vagus nerve stimulation, and repetitive transcranial magnetic stimulation.
 

Useful advice that counters common misconceptions

According to Jacqueline A. French, MD, a professor at NYU Langone Medical Center, Dr. Mula and colleagues are “top notch,” and their recommendations “hit every nail on the head.”

Dr. French, chief medical officer of The Epilepsy Foundation, emphasized the importance of the publication, which addresses two common misconceptions within the medical community: First, that standard antidepressants are insufficient to treat depression in patients with epilepsy, and second, that antidepressants may trigger seizures.

“The first purpose [of the publication] is to say, yes, these antidepressants do work,” Dr. French said, “and no, they don’t worsen seizures, and you can use them safely, and they are appropriate to use.”

Dr. French explained that managing depression remains a practice gap among epileptologists and neurologists because it is a diagnosis that doesn’t traditionally fall into their purview, yet many patients with epilepsy forgo visiting their primary care providers, who more frequently diagnose and manage depression. Dr. French agreed with the guidance that epilepsy specialists should fill this gap.

“We need to at least be able to take people through their first antidepressant, even though we were not trained to be psychiatrists,” Dr. French said. “That’s part of the best care of our patients.”

Imad Najm, MD, director of the Charles Shor Epilepsy Center, Cleveland Clinic, said the recommendations are a step forward in the field, as they are supported by clinical data, instead of just clinical experience and expertise.

Still, Dr. Najm noted that more work is needed to stratify risk of depression in epilepsy and evaluate a possible causal relationship between epilepsy therapies and depression.

He went on to emphasizes the scale of issue at hand, and the stakes involved.

“Depression, anxiety, and psychosis affect a large number of patients with epilepsy,” Dr. Najm said. “Clinical screening and recognition of these comorbidities leads to the institution of treatment options and significant improvement in quality of life. Mental health professionals should be an integral part of any comprehensive epilepsy center.”

The investigators disclosed relationships with Esai, UCB, Elsevier, and others. Dr. French is indirectly involved with multiple pharmaceutical companies developing epilepsy drugs through her role as director of The Epilepsy Study Consortium, a nonprofit organization. Dr. Najm reported no conflicts of interest.

The International League Against Epilepsy (ILAE) has issued recommendations for treating depression in patients with epilepsy.

The new guidance highlights the high prevalence of depression among patients with epilepsy while offering the first systematic approach to treatment, reported lead author Marco Mula, MD, PhD, of Atkinson Morley Regional Neuroscience Centre at St George’s University Hospital, London, and colleagues.

“Despite evidence that depression represents a frequently encountered comorbidity [among patients with epilepsy], data on the treatment of depression in epilepsy [are] still limited and recommendations rely mostly on individual clinical experience and expertise,” the investigators wrote in Epilepsia.

Recommendations cover first-line treatment of unipolar depression in epilepsy without other psychiatric disorders.

For patients with mild depression, the guidance supports psychological intervention without pharmacologic therapy; however, if the patient wishes to use medication, has had a positive response to medication in the past, or nonpharmacologic treatments have previously failed or are unavailable, then SSRIs should be considered first-choice therapy. For moderate to severe depression, SSRIs are the first choice, according to Dr. Mula and colleagues.

“It has to be acknowledged that there is considerable debate in the psychiatric literature about the treatment of mild depression in adults,” the investigators noted. “A patient-level meta-analysis pointed out that the magnitude of benefit of antidepressant medications compared with placebo increases with severity of depression symptoms and it may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.”

If a patient does not respond to first-line therapy, then venlafaxine should be considered, according to the guidance. When a patient does respond to therapy, treatment should be continued for at least 6 months, and when residual symptoms persist, treatment should be continued until resolution.

“In people with depression it is established that around two-thirds of patients do not achieve full remission with first-line treatment,” Dr. Mula and colleagues wrote. “In people with epilepsy, current data show that up to 50% of patients do not achieve full remission from depression. For this reason, augmentation strategies are often needed. They should be adopted by psychiatrists, neuropsychiatrists, or mental health professionals familiar with such therapeutic strategies.”

Beyond these key recommendations, the guidance covers a range of additional topics, including other pharmacologic options, medication discontinuation strategies, electroconvulsive therapy, light therapy, exercise training, vagus nerve stimulation, and repetitive transcranial magnetic stimulation.
 

Useful advice that counters common misconceptions

According to Jacqueline A. French, MD, a professor at NYU Langone Medical Center, Dr. Mula and colleagues are “top notch,” and their recommendations “hit every nail on the head.”

Dr. French, chief medical officer of The Epilepsy Foundation, emphasized the importance of the publication, which addresses two common misconceptions within the medical community: First, that standard antidepressants are insufficient to treat depression in patients with epilepsy, and second, that antidepressants may trigger seizures.

“The first purpose [of the publication] is to say, yes, these antidepressants do work,” Dr. French said, “and no, they don’t worsen seizures, and you can use them safely, and they are appropriate to use.”

Dr. French explained that managing depression remains a practice gap among epileptologists and neurologists because it is a diagnosis that doesn’t traditionally fall into their purview, yet many patients with epilepsy forgo visiting their primary care providers, who more frequently diagnose and manage depression. Dr. French agreed with the guidance that epilepsy specialists should fill this gap.

“We need to at least be able to take people through their first antidepressant, even though we were not trained to be psychiatrists,” Dr. French said. “That’s part of the best care of our patients.”

Imad Najm, MD, director of the Charles Shor Epilepsy Center, Cleveland Clinic, said the recommendations are a step forward in the field, as they are supported by clinical data, instead of just clinical experience and expertise.

Still, Dr. Najm noted that more work is needed to stratify risk of depression in epilepsy and evaluate a possible causal relationship between epilepsy therapies and depression.

He went on to emphasizes the scale of issue at hand, and the stakes involved.

“Depression, anxiety, and psychosis affect a large number of patients with epilepsy,” Dr. Najm said. “Clinical screening and recognition of these comorbidities leads to the institution of treatment options and significant improvement in quality of life. Mental health professionals should be an integral part of any comprehensive epilepsy center.”

The investigators disclosed relationships with Esai, UCB, Elsevier, and others. Dr. French is indirectly involved with multiple pharmaceutical companies developing epilepsy drugs through her role as director of The Epilepsy Study Consortium, a nonprofit organization. Dr. Najm reported no conflicts of interest.