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More brain aging observed in older patients with child-onset epilepsy

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While the meaning of the findings aren’t entirely clear, new research offers insight into the aging brains of people who developed child-onset epilepsy: A cohort with an average age of 63 appears to be more likely than controls to show signs of brain deterioration, according to a study presented at the annual meeting of the American Epilepsy Society.

A more abnormal aging course was seen among those with continuing active epilepsy, those with focal epilepsy compared with generalized epilepsies, and those who had the highest lifetime load of specific anti-epilepsy medications,” lead author Matti Sillanpää, MD, PhD, a researcher and former child neurologist based at the University of Turko in Finland, said in an interview.

The study began 60 years ago when Finnish researchers started to track 99 subjects who were under 16 and had developed uncomplicated epilepsy. In 2012, 51 participants returned for assessments (9 of the original cohort had died, 2 didn’t speak Finnish as a mother tongue, and 15 had left the country or couldn’t be found).

In 2017, 41 participants agreed to take part in follow-up assessments (1 of the 2012 cohort could not be traced, and 9 declined to participate.)

Researchers launched the follow-up assessments to provide more insight into aging and epilepsy, Dr. Sillanpää said. “While we are in the early stages of understanding the brain and cognitive aging processes of people with epilepsy, there are enough worrisome signs from neuroimaging and cognitive studies to suggest that much more clinical and research attention is warranted. Especially important are population-based investigations that include persons with both remitted as well as active epilepsy in order to obtain a clearer understanding of the overall aging risks involved.”

The average age of the 41 subjects in the second assessment was 63.2 (4.1), and 58% were female. Just over half (52%) had focal epilepsy, and 48% had generalized epilepsy. In 74%, epilepsy had remitted, and it remained active in the rest (26%).

For the study, researchers compared the subjects with a control group of 46 subjects, 50% of whom were female, with an average age of 63.0 (4.13). The original control group had 99 participants, and 52 took part in 2012. Of those, 6 declined to participate in the 2017 assessments.

The researchers report these findings:

  • Patients with active epilepsy were more likely to have neurologic signs than were those with remitted epilepsy (P = .015), especially the most common signs – cerebellar signs (P < .001). There was a trend toward cerebellar atrophy but it wasn’t statistically significant (P = .06).
  • Patients with focal epilepsies were more likely to have neurologic signs (P = .008) and, specifically, cerebellar signs (P = .018) than were those with generalized epilepsies.
  • The study authors calculated the lifetime usage of four drugs: carbamazepine, diphenylhydantoin, phenobarbital, and valproate. They found that patients with higher usage had more peripheral neuropathy, especially those with high levels of diphenylhydantoin, and phenobarbital usage.
  • Overall, patients with epilepsy versus controls and those with active epilepsy versus remitting epilepsy were more likely to show adjusted declines in “cognitive trajectories” (both P < .05)
 

 

The researchers also estimated beta-amyloid levels via Pittsburgh Compound B positron emission tomography (PIB-PET); some specialists consider PIB-positive levels to be a sign of more beta amyloid.

From 2012 to 2017, the percentage of patients with epilepsy who were PIB positive grew from 22% to 33% (P = .03), while the percentage grew from 7% to 11% in the controls (P = .04). “The presence of amyloid and increasing positivity is cause for concern, and further research into the course of the participants is critical,” Dr. Sillanpää said.

It’s not clear if higher levels of brain aging are affecting the lives of participants, he said. “No one in the cohort has a diagnosed dementia at present, but going forward it will be important to pay close attention to the day-to-day functional status of participants.”

The mechanisms that may cause more brain aging in epilepsy aren’t known. However, “the CDC has shown through population-based investigations that people with epilepsy as a group may be more socially isolated, more physically inactive, and may harbor other lifestyle issues that we now know to be counterproductive to successful cognitive and brain aging in the general population,” Dr. Sillanpää said. “These factors need to be examined in depth in aging persons with epilepsy to gain a sound understanding of the risk and resilience factors that are most important so that people with epilepsy can act accordingly.”

The researchers also report that in patients with epilepsy, there’s evidence of a link between hypertension and hippocampal atrophy. They reported trends toward links between obesity and ischemic disease and between type 2 diabetes and hippocampal atrophy.

Going forward, “the findings may be helpful in the treatment and counseling of patients with epilepsy and especially advocating for those health and lifestyle practices that may be beneficial to long-term courses,” Dr. Sillanpää said. As for the study cohort, he said, researchers plan to continue monitoring them to track their long-term outcomes and any development of neurological disorders such as Alzheimer’s disease.

This work was funded by CURE Epilepsy, the National Governmental Research Grant, and the Pro Humanitate Foundation Grant. The study authors report no disclosures.

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While the meaning of the findings aren’t entirely clear, new research offers insight into the aging brains of people who developed child-onset epilepsy: A cohort with an average age of 63 appears to be more likely than controls to show signs of brain deterioration, according to a study presented at the annual meeting of the American Epilepsy Society.

A more abnormal aging course was seen among those with continuing active epilepsy, those with focal epilepsy compared with generalized epilepsies, and those who had the highest lifetime load of specific anti-epilepsy medications,” lead author Matti Sillanpää, MD, PhD, a researcher and former child neurologist based at the University of Turko in Finland, said in an interview.

The study began 60 years ago when Finnish researchers started to track 99 subjects who were under 16 and had developed uncomplicated epilepsy. In 2012, 51 participants returned for assessments (9 of the original cohort had died, 2 didn’t speak Finnish as a mother tongue, and 15 had left the country or couldn’t be found).

In 2017, 41 participants agreed to take part in follow-up assessments (1 of the 2012 cohort could not be traced, and 9 declined to participate.)

Researchers launched the follow-up assessments to provide more insight into aging and epilepsy, Dr. Sillanpää said. “While we are in the early stages of understanding the brain and cognitive aging processes of people with epilepsy, there are enough worrisome signs from neuroimaging and cognitive studies to suggest that much more clinical and research attention is warranted. Especially important are population-based investigations that include persons with both remitted as well as active epilepsy in order to obtain a clearer understanding of the overall aging risks involved.”

The average age of the 41 subjects in the second assessment was 63.2 (4.1), and 58% were female. Just over half (52%) had focal epilepsy, and 48% had generalized epilepsy. In 74%, epilepsy had remitted, and it remained active in the rest (26%).

For the study, researchers compared the subjects with a control group of 46 subjects, 50% of whom were female, with an average age of 63.0 (4.13). The original control group had 99 participants, and 52 took part in 2012. Of those, 6 declined to participate in the 2017 assessments.

The researchers report these findings:

  • Patients with active epilepsy were more likely to have neurologic signs than were those with remitted epilepsy (P = .015), especially the most common signs – cerebellar signs (P < .001). There was a trend toward cerebellar atrophy but it wasn’t statistically significant (P = .06).
  • Patients with focal epilepsies were more likely to have neurologic signs (P = .008) and, specifically, cerebellar signs (P = .018) than were those with generalized epilepsies.
  • The study authors calculated the lifetime usage of four drugs: carbamazepine, diphenylhydantoin, phenobarbital, and valproate. They found that patients with higher usage had more peripheral neuropathy, especially those with high levels of diphenylhydantoin, and phenobarbital usage.
  • Overall, patients with epilepsy versus controls and those with active epilepsy versus remitting epilepsy were more likely to show adjusted declines in “cognitive trajectories” (both P < .05)
 

 

The researchers also estimated beta-amyloid levels via Pittsburgh Compound B positron emission tomography (PIB-PET); some specialists consider PIB-positive levels to be a sign of more beta amyloid.

From 2012 to 2017, the percentage of patients with epilepsy who were PIB positive grew from 22% to 33% (P = .03), while the percentage grew from 7% to 11% in the controls (P = .04). “The presence of amyloid and increasing positivity is cause for concern, and further research into the course of the participants is critical,” Dr. Sillanpää said.

It’s not clear if higher levels of brain aging are affecting the lives of participants, he said. “No one in the cohort has a diagnosed dementia at present, but going forward it will be important to pay close attention to the day-to-day functional status of participants.”

The mechanisms that may cause more brain aging in epilepsy aren’t known. However, “the CDC has shown through population-based investigations that people with epilepsy as a group may be more socially isolated, more physically inactive, and may harbor other lifestyle issues that we now know to be counterproductive to successful cognitive and brain aging in the general population,” Dr. Sillanpää said. “These factors need to be examined in depth in aging persons with epilepsy to gain a sound understanding of the risk and resilience factors that are most important so that people with epilepsy can act accordingly.”

The researchers also report that in patients with epilepsy, there’s evidence of a link between hypertension and hippocampal atrophy. They reported trends toward links between obesity and ischemic disease and between type 2 diabetes and hippocampal atrophy.

Going forward, “the findings may be helpful in the treatment and counseling of patients with epilepsy and especially advocating for those health and lifestyle practices that may be beneficial to long-term courses,” Dr. Sillanpää said. As for the study cohort, he said, researchers plan to continue monitoring them to track their long-term outcomes and any development of neurological disorders such as Alzheimer’s disease.

This work was funded by CURE Epilepsy, the National Governmental Research Grant, and the Pro Humanitate Foundation Grant. The study authors report no disclosures.

While the meaning of the findings aren’t entirely clear, new research offers insight into the aging brains of people who developed child-onset epilepsy: A cohort with an average age of 63 appears to be more likely than controls to show signs of brain deterioration, according to a study presented at the annual meeting of the American Epilepsy Society.

A more abnormal aging course was seen among those with continuing active epilepsy, those with focal epilepsy compared with generalized epilepsies, and those who had the highest lifetime load of specific anti-epilepsy medications,” lead author Matti Sillanpää, MD, PhD, a researcher and former child neurologist based at the University of Turko in Finland, said in an interview.

The study began 60 years ago when Finnish researchers started to track 99 subjects who were under 16 and had developed uncomplicated epilepsy. In 2012, 51 participants returned for assessments (9 of the original cohort had died, 2 didn’t speak Finnish as a mother tongue, and 15 had left the country or couldn’t be found).

In 2017, 41 participants agreed to take part in follow-up assessments (1 of the 2012 cohort could not be traced, and 9 declined to participate.)

Researchers launched the follow-up assessments to provide more insight into aging and epilepsy, Dr. Sillanpää said. “While we are in the early stages of understanding the brain and cognitive aging processes of people with epilepsy, there are enough worrisome signs from neuroimaging and cognitive studies to suggest that much more clinical and research attention is warranted. Especially important are population-based investigations that include persons with both remitted as well as active epilepsy in order to obtain a clearer understanding of the overall aging risks involved.”

The average age of the 41 subjects in the second assessment was 63.2 (4.1), and 58% were female. Just over half (52%) had focal epilepsy, and 48% had generalized epilepsy. In 74%, epilepsy had remitted, and it remained active in the rest (26%).

For the study, researchers compared the subjects with a control group of 46 subjects, 50% of whom were female, with an average age of 63.0 (4.13). The original control group had 99 participants, and 52 took part in 2012. Of those, 6 declined to participate in the 2017 assessments.

The researchers report these findings:

  • Patients with active epilepsy were more likely to have neurologic signs than were those with remitted epilepsy (P = .015), especially the most common signs – cerebellar signs (P < .001). There was a trend toward cerebellar atrophy but it wasn’t statistically significant (P = .06).
  • Patients with focal epilepsies were more likely to have neurologic signs (P = .008) and, specifically, cerebellar signs (P = .018) than were those with generalized epilepsies.
  • The study authors calculated the lifetime usage of four drugs: carbamazepine, diphenylhydantoin, phenobarbital, and valproate. They found that patients with higher usage had more peripheral neuropathy, especially those with high levels of diphenylhydantoin, and phenobarbital usage.
  • Overall, patients with epilepsy versus controls and those with active epilepsy versus remitting epilepsy were more likely to show adjusted declines in “cognitive trajectories” (both P < .05)
 

 

The researchers also estimated beta-amyloid levels via Pittsburgh Compound B positron emission tomography (PIB-PET); some specialists consider PIB-positive levels to be a sign of more beta amyloid.

From 2012 to 2017, the percentage of patients with epilepsy who were PIB positive grew from 22% to 33% (P = .03), while the percentage grew from 7% to 11% in the controls (P = .04). “The presence of amyloid and increasing positivity is cause for concern, and further research into the course of the participants is critical,” Dr. Sillanpää said.

It’s not clear if higher levels of brain aging are affecting the lives of participants, he said. “No one in the cohort has a diagnosed dementia at present, but going forward it will be important to pay close attention to the day-to-day functional status of participants.”

The mechanisms that may cause more brain aging in epilepsy aren’t known. However, “the CDC has shown through population-based investigations that people with epilepsy as a group may be more socially isolated, more physically inactive, and may harbor other lifestyle issues that we now know to be counterproductive to successful cognitive and brain aging in the general population,” Dr. Sillanpää said. “These factors need to be examined in depth in aging persons with epilepsy to gain a sound understanding of the risk and resilience factors that are most important so that people with epilepsy can act accordingly.”

The researchers also report that in patients with epilepsy, there’s evidence of a link between hypertension and hippocampal atrophy. They reported trends toward links between obesity and ischemic disease and between type 2 diabetes and hippocampal atrophy.

Going forward, “the findings may be helpful in the treatment and counseling of patients with epilepsy and especially advocating for those health and lifestyle practices that may be beneficial to long-term courses,” Dr. Sillanpää said. As for the study cohort, he said, researchers plan to continue monitoring them to track their long-term outcomes and any development of neurological disorders such as Alzheimer’s disease.

This work was funded by CURE Epilepsy, the National Governmental Research Grant, and the Pro Humanitate Foundation Grant. The study authors report no disclosures.

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New insights into psychogenic seizures in teens

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Adolescents with psychogenic nonepileptic seizures (PNES) experience severe bullying by fellow students and school staff alike, results of a small study suggest.

The school experience of teens with PNES is overwhelmingly negative, study investigator Andrea Tanner, PhD, a postdoctoral fellow at Indiana University School of Nursing, Indianapolis.

She hopes this research will spur a collaborative effort between students, schools, families, and health care providers “to develop an effective plan to help these adolescents cope, to manage this condition, and hopefully reach seizure freedom.”

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Anxiety, perfectionism

Although psychogenic seizures resemble epileptic seizures, they have a psychological basis and, unlike epilepsy, are not caused by abnormal electrical brain activity.

While the school experience has previously been identified as a source of predisposing, precipitating, and perpetuating factors for PNES, little is known about the school experience of adolescents with the disorder and the role it may play in PNES management, the investigators noted.

During her 20 years as a school nurse, Dr. Tanner saw firsthand how school staff struggled with responding appropriately to teens with PNES. “They wanted to call 911 every time; they wanted to respond as if it [were] an epileptic seizure.”

For the study, she interviewed 10 teens with PNES, aged 12 to 19 years, whom she found mostly through Facebook support groups but also through flyers. All participants had undergone video EEG and been diagnosed with PNES.

From the interviews, Dr. Tanner and colleagues conducted a qualitative content analysis and uncovered “overarching” themes.

A main theme was stress, some of which focused on bullying by peers or harassment by school personnel, much of which was related to accusations of the children “faking” seizures to get attention, said Dr. Tanner.

Some teens reported being banned from school events, such as field trips, out of concern they would be a “distraction,” which led to feelings of isolation and exclusion, said Dr. Tanner.

Research points to a growing incidence of PNES among adolescents. This may be because it is now better recognized, or it may stem from the unique stressors today’s teens face, said Dr. Tanner.

Adolescents discussed the pressures they feel to be the best at everything. “They wanted to be good in athletics; they wanted to be good in academics; they wanted to get into a good college,” said Dr. Tanner.

Some study participants had undergone psychotherapy, including cognitive-behavioral therapy, and others had investigated mindfulness-based therapy. However, not all were receiving treatment. For some, such care was inaccessible, while others had tried a mental health care intervention but had abandoned it.

Although all the study participants were female, Dr. Tanner has interviewed males outside this study and found their experiences are similar.

Her next research step is to try to quantify the findings. “I would like to begin to look at what would be the appropriate outcomes if I were to do an intervention to improve the school experience.”

Her message for doctors is to see school nurses as a “partner” or “liaison” who “can bridge the world of health care and education.”
 

 

 

Important, novel research

Commenting on the research, Barbara Dworetzky, MD, Chief, Epilepsy, Brigham and Women’s Hospital, and professor of neurology, Harvard Medical School, said it’s “important and novel.”

The study focuses on the main factors – or themes – that lead to increased stress, such as bullying, isolation, and “not being believed,” that are likely triggers for PNES, said Dr. Dworetzky.

The study is also important because it focuses on factors that help make the girls “feel supported and protected” – for example, having staff “take the episodes seriously,” she said.

The study’s qualitative measures “are a valid way of understanding these girls and giving them a voice,” said Dr. Dworetzky. She added the study provides “practical information” that could help target treatments to improve outcomes in this group.

A limitation of the study was that the very small cohort of teenage girls was selected only through families in Facebook support groups or flyers to school nurses, said Dr. Dworetzky.

“There are likely many other groups who don’t even have families trying to help them. Larger cohorts without this type of bias may be next steps.”

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

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Adolescents with psychogenic nonepileptic seizures (PNES) experience severe bullying by fellow students and school staff alike, results of a small study suggest.

The school experience of teens with PNES is overwhelmingly negative, study investigator Andrea Tanner, PhD, a postdoctoral fellow at Indiana University School of Nursing, Indianapolis.

She hopes this research will spur a collaborative effort between students, schools, families, and health care providers “to develop an effective plan to help these adolescents cope, to manage this condition, and hopefully reach seizure freedom.”

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Anxiety, perfectionism

Although psychogenic seizures resemble epileptic seizures, they have a psychological basis and, unlike epilepsy, are not caused by abnormal electrical brain activity.

While the school experience has previously been identified as a source of predisposing, precipitating, and perpetuating factors for PNES, little is known about the school experience of adolescents with the disorder and the role it may play in PNES management, the investigators noted.

During her 20 years as a school nurse, Dr. Tanner saw firsthand how school staff struggled with responding appropriately to teens with PNES. “They wanted to call 911 every time; they wanted to respond as if it [were] an epileptic seizure.”

For the study, she interviewed 10 teens with PNES, aged 12 to 19 years, whom she found mostly through Facebook support groups but also through flyers. All participants had undergone video EEG and been diagnosed with PNES.

From the interviews, Dr. Tanner and colleagues conducted a qualitative content analysis and uncovered “overarching” themes.

A main theme was stress, some of which focused on bullying by peers or harassment by school personnel, much of which was related to accusations of the children “faking” seizures to get attention, said Dr. Tanner.

Some teens reported being banned from school events, such as field trips, out of concern they would be a “distraction,” which led to feelings of isolation and exclusion, said Dr. Tanner.

Research points to a growing incidence of PNES among adolescents. This may be because it is now better recognized, or it may stem from the unique stressors today’s teens face, said Dr. Tanner.

Adolescents discussed the pressures they feel to be the best at everything. “They wanted to be good in athletics; they wanted to be good in academics; they wanted to get into a good college,” said Dr. Tanner.

Some study participants had undergone psychotherapy, including cognitive-behavioral therapy, and others had investigated mindfulness-based therapy. However, not all were receiving treatment. For some, such care was inaccessible, while others had tried a mental health care intervention but had abandoned it.

Although all the study participants were female, Dr. Tanner has interviewed males outside this study and found their experiences are similar.

Her next research step is to try to quantify the findings. “I would like to begin to look at what would be the appropriate outcomes if I were to do an intervention to improve the school experience.”

Her message for doctors is to see school nurses as a “partner” or “liaison” who “can bridge the world of health care and education.”
 

 

 

Important, novel research

Commenting on the research, Barbara Dworetzky, MD, Chief, Epilepsy, Brigham and Women’s Hospital, and professor of neurology, Harvard Medical School, said it’s “important and novel.”

The study focuses on the main factors – or themes – that lead to increased stress, such as bullying, isolation, and “not being believed,” that are likely triggers for PNES, said Dr. Dworetzky.

The study is also important because it focuses on factors that help make the girls “feel supported and protected” – for example, having staff “take the episodes seriously,” she said.

The study’s qualitative measures “are a valid way of understanding these girls and giving them a voice,” said Dr. Dworetzky. She added the study provides “practical information” that could help target treatments to improve outcomes in this group.

A limitation of the study was that the very small cohort of teenage girls was selected only through families in Facebook support groups or flyers to school nurses, said Dr. Dworetzky.

“There are likely many other groups who don’t even have families trying to help them. Larger cohorts without this type of bias may be next steps.”

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

Adolescents with psychogenic nonepileptic seizures (PNES) experience severe bullying by fellow students and school staff alike, results of a small study suggest.

The school experience of teens with PNES is overwhelmingly negative, study investigator Andrea Tanner, PhD, a postdoctoral fellow at Indiana University School of Nursing, Indianapolis.

She hopes this research will spur a collaborative effort between students, schools, families, and health care providers “to develop an effective plan to help these adolescents cope, to manage this condition, and hopefully reach seizure freedom.”

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Anxiety, perfectionism

Although psychogenic seizures resemble epileptic seizures, they have a psychological basis and, unlike epilepsy, are not caused by abnormal electrical brain activity.

While the school experience has previously been identified as a source of predisposing, precipitating, and perpetuating factors for PNES, little is known about the school experience of adolescents with the disorder and the role it may play in PNES management, the investigators noted.

During her 20 years as a school nurse, Dr. Tanner saw firsthand how school staff struggled with responding appropriately to teens with PNES. “They wanted to call 911 every time; they wanted to respond as if it [were] an epileptic seizure.”

For the study, she interviewed 10 teens with PNES, aged 12 to 19 years, whom she found mostly through Facebook support groups but also through flyers. All participants had undergone video EEG and been diagnosed with PNES.

From the interviews, Dr. Tanner and colleagues conducted a qualitative content analysis and uncovered “overarching” themes.

A main theme was stress, some of which focused on bullying by peers or harassment by school personnel, much of which was related to accusations of the children “faking” seizures to get attention, said Dr. Tanner.

Some teens reported being banned from school events, such as field trips, out of concern they would be a “distraction,” which led to feelings of isolation and exclusion, said Dr. Tanner.

Research points to a growing incidence of PNES among adolescents. This may be because it is now better recognized, or it may stem from the unique stressors today’s teens face, said Dr. Tanner.

Adolescents discussed the pressures they feel to be the best at everything. “They wanted to be good in athletics; they wanted to be good in academics; they wanted to get into a good college,” said Dr. Tanner.

Some study participants had undergone psychotherapy, including cognitive-behavioral therapy, and others had investigated mindfulness-based therapy. However, not all were receiving treatment. For some, such care was inaccessible, while others had tried a mental health care intervention but had abandoned it.

Although all the study participants were female, Dr. Tanner has interviewed males outside this study and found their experiences are similar.

Her next research step is to try to quantify the findings. “I would like to begin to look at what would be the appropriate outcomes if I were to do an intervention to improve the school experience.”

Her message for doctors is to see school nurses as a “partner” or “liaison” who “can bridge the world of health care and education.”
 

 

 

Important, novel research

Commenting on the research, Barbara Dworetzky, MD, Chief, Epilepsy, Brigham and Women’s Hospital, and professor of neurology, Harvard Medical School, said it’s “important and novel.”

The study focuses on the main factors – or themes – that lead to increased stress, such as bullying, isolation, and “not being believed,” that are likely triggers for PNES, said Dr. Dworetzky.

The study is also important because it focuses on factors that help make the girls “feel supported and protected” – for example, having staff “take the episodes seriously,” she said.

The study’s qualitative measures “are a valid way of understanding these girls and giving them a voice,” said Dr. Dworetzky. She added the study provides “practical information” that could help target treatments to improve outcomes in this group.

A limitation of the study was that the very small cohort of teenage girls was selected only through families in Facebook support groups or flyers to school nurses, said Dr. Dworetzky.

“There are likely many other groups who don’t even have families trying to help them. Larger cohorts without this type of bias may be next steps.”

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

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‘Alarming’ rate of abuse in pregnant women with epilepsy

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Women with epilepsy are more than twice as likely as those without the disorder to report physical, sexual, or emotional abuse during pregnancy, new research shows.

Study investigator Naveed Chaudhry, MD, a recent epilepsy fellow and assistant professor of neurology, University of Colorado School of Medicine, described the finding as “alarming” and called for more support for this patient population.

Investigators found that women with epilepsy are also more likely to report other stressors, including divorce, illness, lost pay, and partner discord, while expecting.

“As epilepsy physicians, it’s important that we ask the right questions and dive a little bit deeper with these patients, even if it’s uncomfortable and not something we’re used to,” said Dr. Chaudhry.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Cause for concern

Women with epilepsy may be under stress for a variety of social and economic reasons. In some women, stress can trigger seizures, and during pregnancy, this can lead to complications such as preterm labor and low birth weight.

For the study, researchers tapped into the Center for Disease Control and Prevention Pregnancy Risk Assessment and Monitoring System (PRAMS). This database includes information from surveys asking women across the U.S. about their pregnancy and postpartum period.

Thirteen states collected data on stresses in women with and without epilepsy. Respondents were asked about 14 economic and other worries in the year prior to their baby’s birth, including the pregnancy period.

The analysis included 64,951 women, 1,140 of whom had epilepsy, who were included in surveys from 2012-2020. There were no significant demographic differences between those with and those without the disorder.

After adjusting for maternal age, race, ethnicity, marital status, education, and socioeconomic status, the study found that women with epilepsy experienced an average of 2.41 of the stressors compared with 1.72 for women without epilepsy.

Women with epilepsy were more likely to have experienced family illness, divorce, homelessness, partner job loss, reduced work or pay, increased arguments, having a partner in jail, drug use, and the death of someone close to them.

The results showed that unmarried and younger women as well as those with lower incomes were particularly prone to experience stress during pregnancy.

It’s not clear why women with epilepsy report more stressors. “Looking at the literature, no one has really looked at the exact reason for this, but we postulate it could be a lack of supports and support systems,” said Dr. Chaudhry.

Women were asked about physical, sexual, and emotional abuse. Results showed that substantially more women with epilepsy than those without the disorder reported such abuse during pregnancy – 10.6% versus 4.1%. The adjusted odds ratio for women with epilepsy reporting abuse was 2.78 (95% CI, 2.07-3.74).

“That raises our concern and needs to be looked at in more detail,” said Dr. Chaudhry.

It is unclear whether some women might have had psychogenic non-epileptic seizures (PNES), which are linked to a higher rate of abuse, said Dr. Chaudhry. “But the prevalence of PNES in the general population is quite low, so we don’t think it’s contributing to a large extent to this finding.”

The findings highlight the importance of addressing stress in women with epilepsy during pregnancy, he said. “We need to have good support services and we need to counsel women to optimize good outcomes.”

This applies to all women of childbearing age. “We suspect abuse and stressors are going to be going on throughout that period,” said Dr. Chaudhry. “It’s important to ask about it and have appropriate support staff and social work and people available to help when an issue is identified.”
 

 

 

Stress a common seizure trigger

Commenting on the research, Kimford Meador, MD, professor, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, noted the study was well conducted and had a large sample size.

The findings are important, as stress is a common trigger for seizures in people with epilepsy and is associated with mood and anxiety, which can affect quality of life, said Dr. Meador.

Results of his analysis from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, also presented at this year’s AES meeting, showed that women with epilepsy had more depressive symptoms during the postpartum period and more anxiety symptoms during pregnancy and postpartum in comparison with those without epilepsy.

Dr. Meador’s group also recently conducted a study that was published in JAMA Neurology, showing that in women with epilepsy during the postpartum period, anxiety is associated with lower cognitive ability in their children at age 2 years.

“All these findings highlight the importance of assessing and managing stress, anxiety, and mood in women with epilepsy,” said Dr. Meador. “Interventions could impact seizures and quality of life in pregnant women with epilepsy and long-term outcomes in their children.”

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

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Women with epilepsy are more than twice as likely as those without the disorder to report physical, sexual, or emotional abuse during pregnancy, new research shows.

Study investigator Naveed Chaudhry, MD, a recent epilepsy fellow and assistant professor of neurology, University of Colorado School of Medicine, described the finding as “alarming” and called for more support for this patient population.

Investigators found that women with epilepsy are also more likely to report other stressors, including divorce, illness, lost pay, and partner discord, while expecting.

“As epilepsy physicians, it’s important that we ask the right questions and dive a little bit deeper with these patients, even if it’s uncomfortable and not something we’re used to,” said Dr. Chaudhry.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Cause for concern

Women with epilepsy may be under stress for a variety of social and economic reasons. In some women, stress can trigger seizures, and during pregnancy, this can lead to complications such as preterm labor and low birth weight.

For the study, researchers tapped into the Center for Disease Control and Prevention Pregnancy Risk Assessment and Monitoring System (PRAMS). This database includes information from surveys asking women across the U.S. about their pregnancy and postpartum period.

Thirteen states collected data on stresses in women with and without epilepsy. Respondents were asked about 14 economic and other worries in the year prior to their baby’s birth, including the pregnancy period.

The analysis included 64,951 women, 1,140 of whom had epilepsy, who were included in surveys from 2012-2020. There were no significant demographic differences between those with and those without the disorder.

After adjusting for maternal age, race, ethnicity, marital status, education, and socioeconomic status, the study found that women with epilepsy experienced an average of 2.41 of the stressors compared with 1.72 for women without epilepsy.

Women with epilepsy were more likely to have experienced family illness, divorce, homelessness, partner job loss, reduced work or pay, increased arguments, having a partner in jail, drug use, and the death of someone close to them.

The results showed that unmarried and younger women as well as those with lower incomes were particularly prone to experience stress during pregnancy.

It’s not clear why women with epilepsy report more stressors. “Looking at the literature, no one has really looked at the exact reason for this, but we postulate it could be a lack of supports and support systems,” said Dr. Chaudhry.

Women were asked about physical, sexual, and emotional abuse. Results showed that substantially more women with epilepsy than those without the disorder reported such abuse during pregnancy – 10.6% versus 4.1%. The adjusted odds ratio for women with epilepsy reporting abuse was 2.78 (95% CI, 2.07-3.74).

“That raises our concern and needs to be looked at in more detail,” said Dr. Chaudhry.

It is unclear whether some women might have had psychogenic non-epileptic seizures (PNES), which are linked to a higher rate of abuse, said Dr. Chaudhry. “But the prevalence of PNES in the general population is quite low, so we don’t think it’s contributing to a large extent to this finding.”

The findings highlight the importance of addressing stress in women with epilepsy during pregnancy, he said. “We need to have good support services and we need to counsel women to optimize good outcomes.”

This applies to all women of childbearing age. “We suspect abuse and stressors are going to be going on throughout that period,” said Dr. Chaudhry. “It’s important to ask about it and have appropriate support staff and social work and people available to help when an issue is identified.”
 

 

 

Stress a common seizure trigger

Commenting on the research, Kimford Meador, MD, professor, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, noted the study was well conducted and had a large sample size.

The findings are important, as stress is a common trigger for seizures in people with epilepsy and is associated with mood and anxiety, which can affect quality of life, said Dr. Meador.

Results of his analysis from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, also presented at this year’s AES meeting, showed that women with epilepsy had more depressive symptoms during the postpartum period and more anxiety symptoms during pregnancy and postpartum in comparison with those without epilepsy.

Dr. Meador’s group also recently conducted a study that was published in JAMA Neurology, showing that in women with epilepsy during the postpartum period, anxiety is associated with lower cognitive ability in their children at age 2 years.

“All these findings highlight the importance of assessing and managing stress, anxiety, and mood in women with epilepsy,” said Dr. Meador. “Interventions could impact seizures and quality of life in pregnant women with epilepsy and long-term outcomes in their children.”

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

Women with epilepsy are more than twice as likely as those without the disorder to report physical, sexual, or emotional abuse during pregnancy, new research shows.

Study investigator Naveed Chaudhry, MD, a recent epilepsy fellow and assistant professor of neurology, University of Colorado School of Medicine, described the finding as “alarming” and called for more support for this patient population.

Investigators found that women with epilepsy are also more likely to report other stressors, including divorce, illness, lost pay, and partner discord, while expecting.

“As epilepsy physicians, it’s important that we ask the right questions and dive a little bit deeper with these patients, even if it’s uncomfortable and not something we’re used to,” said Dr. Chaudhry.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Cause for concern

Women with epilepsy may be under stress for a variety of social and economic reasons. In some women, stress can trigger seizures, and during pregnancy, this can lead to complications such as preterm labor and low birth weight.

For the study, researchers tapped into the Center for Disease Control and Prevention Pregnancy Risk Assessment and Monitoring System (PRAMS). This database includes information from surveys asking women across the U.S. about their pregnancy and postpartum period.

Thirteen states collected data on stresses in women with and without epilepsy. Respondents were asked about 14 economic and other worries in the year prior to their baby’s birth, including the pregnancy period.

The analysis included 64,951 women, 1,140 of whom had epilepsy, who were included in surveys from 2012-2020. There were no significant demographic differences between those with and those without the disorder.

After adjusting for maternal age, race, ethnicity, marital status, education, and socioeconomic status, the study found that women with epilepsy experienced an average of 2.41 of the stressors compared with 1.72 for women without epilepsy.

Women with epilepsy were more likely to have experienced family illness, divorce, homelessness, partner job loss, reduced work or pay, increased arguments, having a partner in jail, drug use, and the death of someone close to them.

The results showed that unmarried and younger women as well as those with lower incomes were particularly prone to experience stress during pregnancy.

It’s not clear why women with epilepsy report more stressors. “Looking at the literature, no one has really looked at the exact reason for this, but we postulate it could be a lack of supports and support systems,” said Dr. Chaudhry.

Women were asked about physical, sexual, and emotional abuse. Results showed that substantially more women with epilepsy than those without the disorder reported such abuse during pregnancy – 10.6% versus 4.1%. The adjusted odds ratio for women with epilepsy reporting abuse was 2.78 (95% CI, 2.07-3.74).

“That raises our concern and needs to be looked at in more detail,” said Dr. Chaudhry.

It is unclear whether some women might have had psychogenic non-epileptic seizures (PNES), which are linked to a higher rate of abuse, said Dr. Chaudhry. “But the prevalence of PNES in the general population is quite low, so we don’t think it’s contributing to a large extent to this finding.”

The findings highlight the importance of addressing stress in women with epilepsy during pregnancy, he said. “We need to have good support services and we need to counsel women to optimize good outcomes.”

This applies to all women of childbearing age. “We suspect abuse and stressors are going to be going on throughout that period,” said Dr. Chaudhry. “It’s important to ask about it and have appropriate support staff and social work and people available to help when an issue is identified.”
 

 

 

Stress a common seizure trigger

Commenting on the research, Kimford Meador, MD, professor, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, noted the study was well conducted and had a large sample size.

The findings are important, as stress is a common trigger for seizures in people with epilepsy and is associated with mood and anxiety, which can affect quality of life, said Dr. Meador.

Results of his analysis from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, also presented at this year’s AES meeting, showed that women with epilepsy had more depressive symptoms during the postpartum period and more anxiety symptoms during pregnancy and postpartum in comparison with those without epilepsy.

Dr. Meador’s group also recently conducted a study that was published in JAMA Neurology, showing that in women with epilepsy during the postpartum period, anxiety is associated with lower cognitive ability in their children at age 2 years.

“All these findings highlight the importance of assessing and managing stress, anxiety, and mood in women with epilepsy,” said Dr. Meador. “Interventions could impact seizures and quality of life in pregnant women with epilepsy and long-term outcomes in their children.”

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

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Optimal epilepsy care extends well beyond managing seizures

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Mon, 01/03/2022 - 13:23

In addition to high rates of anxiety and mood disorders, epilepsy is associated with several comorbidities, including headache, hypertension, and back pain, new research shows. Investigators also found racial and ethnic disparities in comorbidity prevalence.

“Our study identified that people with epilepsy have complex health care needs that extend well beyond their epilepsy,” said co-investigator Wyatt P. Bensken, a PhD candidate in the Department of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

A vulnerable population

Researchers identified individuals with epilepsy using Medicaid claims from 2010 to 2014. Mr. Bensken noted that the approximately one-third of patients with epilepsy covered by Medicaid represent “the most vulnerable” population with the disorder because they may not be working and often have other disabilities.

Based on an algorithm that puts diagnostic codes into clinically meaningful categories, the investigators focused on 190 conditions.

“A strength of the study was that we were able to cast such a broad net” to capture conditions, Mr. Bensken said.

Anxiety and mood disorders were originally in separate categories but were grouped together “after recognizing that those who had one pretty much had the other,” he added.

The researchers used a machine learning technique known as association rule mining (ARM) to uncover frequently occurring conditions and combinations of conditions. This same statistical technique is used by companies such as Amazon to determine future purchases based on articles people have bought.

Among 81,963 patients with epilepsy, the most common conditions were anxiety and mood disorders (46.5%). These were followed by hypertension (36.9%), back problems (35.2%), developmental disorders (31.6%), and headache including migraine (29.5%). Urinary tract infections (UTIs) were experienced by 22.8% of the sample.

The rate of anxiety and mood disorders was not unexpected, “but I was surprised to see hypertension so high on the list,” said Mr. Bensken. He noted there is also increasing evidence pointing to a cardiovascular-epilepsy connection.
 

What should neurologists do?

The study also highlights the relatively high rate of back problems, which are not usually considered a comorbidity in patients with epilepsy, Mr. Bensken said. “Back problems likely greatly impact a patient’s quality of life, and seeing them so high on the list makes me wonder if neurologists or epileptologists or primary care doctors are even asking about back pain and how that might impact the ability to function day to day,” he added.

How do these rates compare with the general population? From other studies, the estimated prevalence for anxiety and mood disorders is 20%-30%, compared with almost 50% of the current sample, said Mr. Bensken.

In addition, the rate of hypertension in the study’s epilepsy population was about 7% higher than the general population, and the rate of UTIs was about 12% higher, he reported.

When examining combinations of conditions, anxiety and mood disorders continued to have an “outsized” prevalence, appearing in nearly every combination, the investigators noted.

Almost a quarter (24.7%) of participants had back problems plus anxiety and a mood disorder, and about 15% had headaches and back problems as well as anxiety and a mood disorder.

“That’s a non-negligible amount of the population that have not just one or two things going on but three and four,” said Mr. Bensken.

These new results underscore how complex these patients can be and the need to integrate medical care among different specialties, he noted.

“We don’t believe it’s the neurologist’s job to also manage the hypertension, but being aware of how prevalent hypertension may be and working with the primary care doctor, or at least checking in with the patient and asking if they’re managing their hypertension, is a real priority,” he said.

Researchers also used the ARM system to identify racial disparities, “which have been largely understudied in the epilepsy context,” said Mr. Bensken.

American Indians and Alaskan Natives had a substantially higher prevalence of developmental disabilities, while Black participants had a higher prevalence of hypertension.

One of the study’s themes was that disparities were not uniform, Mr. Bensken noted. “It wasn’t that in every condition the prevalence was lowest for White individuals and highest for everybody else,” he said.

These results point to the need for a larger study to examine the cultural context of these subgroups and such things as structural racism that might drive disparities, he added.

When researchers examined combinations of comorbidities in individuals in the top quartile of hospitalizations and emergency department visits, they found high users had a much higher disease burden, with 75.8% having anxiety or a mood disorder.

The study highlights that patients with epilepsy on Medicaid are “a high priority population,” said Mr. Bensken.
 

 

 

‘Drift down hypothesis’

Commenting on the findings, Fred A. Lado, MD, PhD, director of epilepsy at Northwell Health Eastern and Central Regions, said the increased incidence of comorbidities in patients of low socioeconomic status was not surprising.

“The interesting data here is that we see an even higher incidence among people with epilepsy,” said Dr. Lado, who was not involved with the research.

The study shows how epilepsy exacerbates the effects of low socioeconomic status, he added.

“One of the determinants of socioeconomic status in this case may well be the fact they have seizures and have a limited ability to work and are often more dependent on state assistance and disability support,” Dr. Lado said.

He also referred to the “drift down hypothesis” of chronic disease. “If you have epilepsy and are born into a middle-class family, chances are you will be on disability and can’t work, so you probably have a lower socioeconomic status than your family did as you grew up.”

Dr. Lado noted how “extremely common” mood disorders are in this population and that certain pain syndromes “tracked with those mood disorders.”

“We know mood disorders are more prevalent in people with epilepsy, and now we see that pain-related problems – headache and back pain – are more prevalent in people with epilepsy,” he said.

The data showing “downstream effects of the mood disorders,” from epilepsy to mood disorders to pain disorders, was “very interesting,” Dr. Lado said.

The study was funded by the Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities of the National Institutes of Health. Mr. Bensken has reported receiving research support for this work from the NIH.

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

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In addition to high rates of anxiety and mood disorders, epilepsy is associated with several comorbidities, including headache, hypertension, and back pain, new research shows. Investigators also found racial and ethnic disparities in comorbidity prevalence.

“Our study identified that people with epilepsy have complex health care needs that extend well beyond their epilepsy,” said co-investigator Wyatt P. Bensken, a PhD candidate in the Department of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

A vulnerable population

Researchers identified individuals with epilepsy using Medicaid claims from 2010 to 2014. Mr. Bensken noted that the approximately one-third of patients with epilepsy covered by Medicaid represent “the most vulnerable” population with the disorder because they may not be working and often have other disabilities.

Based on an algorithm that puts diagnostic codes into clinically meaningful categories, the investigators focused on 190 conditions.

“A strength of the study was that we were able to cast such a broad net” to capture conditions, Mr. Bensken said.

Anxiety and mood disorders were originally in separate categories but were grouped together “after recognizing that those who had one pretty much had the other,” he added.

The researchers used a machine learning technique known as association rule mining (ARM) to uncover frequently occurring conditions and combinations of conditions. This same statistical technique is used by companies such as Amazon to determine future purchases based on articles people have bought.

Among 81,963 patients with epilepsy, the most common conditions were anxiety and mood disorders (46.5%). These were followed by hypertension (36.9%), back problems (35.2%), developmental disorders (31.6%), and headache including migraine (29.5%). Urinary tract infections (UTIs) were experienced by 22.8% of the sample.

The rate of anxiety and mood disorders was not unexpected, “but I was surprised to see hypertension so high on the list,” said Mr. Bensken. He noted there is also increasing evidence pointing to a cardiovascular-epilepsy connection.
 

What should neurologists do?

The study also highlights the relatively high rate of back problems, which are not usually considered a comorbidity in patients with epilepsy, Mr. Bensken said. “Back problems likely greatly impact a patient’s quality of life, and seeing them so high on the list makes me wonder if neurologists or epileptologists or primary care doctors are even asking about back pain and how that might impact the ability to function day to day,” he added.

How do these rates compare with the general population? From other studies, the estimated prevalence for anxiety and mood disorders is 20%-30%, compared with almost 50% of the current sample, said Mr. Bensken.

In addition, the rate of hypertension in the study’s epilepsy population was about 7% higher than the general population, and the rate of UTIs was about 12% higher, he reported.

When examining combinations of conditions, anxiety and mood disorders continued to have an “outsized” prevalence, appearing in nearly every combination, the investigators noted.

Almost a quarter (24.7%) of participants had back problems plus anxiety and a mood disorder, and about 15% had headaches and back problems as well as anxiety and a mood disorder.

“That’s a non-negligible amount of the population that have not just one or two things going on but three and four,” said Mr. Bensken.

These new results underscore how complex these patients can be and the need to integrate medical care among different specialties, he noted.

“We don’t believe it’s the neurologist’s job to also manage the hypertension, but being aware of how prevalent hypertension may be and working with the primary care doctor, or at least checking in with the patient and asking if they’re managing their hypertension, is a real priority,” he said.

Researchers also used the ARM system to identify racial disparities, “which have been largely understudied in the epilepsy context,” said Mr. Bensken.

American Indians and Alaskan Natives had a substantially higher prevalence of developmental disabilities, while Black participants had a higher prevalence of hypertension.

One of the study’s themes was that disparities were not uniform, Mr. Bensken noted. “It wasn’t that in every condition the prevalence was lowest for White individuals and highest for everybody else,” he said.

These results point to the need for a larger study to examine the cultural context of these subgroups and such things as structural racism that might drive disparities, he added.

When researchers examined combinations of comorbidities in individuals in the top quartile of hospitalizations and emergency department visits, they found high users had a much higher disease burden, with 75.8% having anxiety or a mood disorder.

The study highlights that patients with epilepsy on Medicaid are “a high priority population,” said Mr. Bensken.
 

 

 

‘Drift down hypothesis’

Commenting on the findings, Fred A. Lado, MD, PhD, director of epilepsy at Northwell Health Eastern and Central Regions, said the increased incidence of comorbidities in patients of low socioeconomic status was not surprising.

“The interesting data here is that we see an even higher incidence among people with epilepsy,” said Dr. Lado, who was not involved with the research.

The study shows how epilepsy exacerbates the effects of low socioeconomic status, he added.

“One of the determinants of socioeconomic status in this case may well be the fact they have seizures and have a limited ability to work and are often more dependent on state assistance and disability support,” Dr. Lado said.

He also referred to the “drift down hypothesis” of chronic disease. “If you have epilepsy and are born into a middle-class family, chances are you will be on disability and can’t work, so you probably have a lower socioeconomic status than your family did as you grew up.”

Dr. Lado noted how “extremely common” mood disorders are in this population and that certain pain syndromes “tracked with those mood disorders.”

“We know mood disorders are more prevalent in people with epilepsy, and now we see that pain-related problems – headache and back pain – are more prevalent in people with epilepsy,” he said.

The data showing “downstream effects of the mood disorders,” from epilepsy to mood disorders to pain disorders, was “very interesting,” Dr. Lado said.

The study was funded by the Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities of the National Institutes of Health. Mr. Bensken has reported receiving research support for this work from the NIH.

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

In addition to high rates of anxiety and mood disorders, epilepsy is associated with several comorbidities, including headache, hypertension, and back pain, new research shows. Investigators also found racial and ethnic disparities in comorbidity prevalence.

“Our study identified that people with epilepsy have complex health care needs that extend well beyond their epilepsy,” said co-investigator Wyatt P. Bensken, a PhD candidate in the Department of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

A vulnerable population

Researchers identified individuals with epilepsy using Medicaid claims from 2010 to 2014. Mr. Bensken noted that the approximately one-third of patients with epilepsy covered by Medicaid represent “the most vulnerable” population with the disorder because they may not be working and often have other disabilities.

Based on an algorithm that puts diagnostic codes into clinically meaningful categories, the investigators focused on 190 conditions.

“A strength of the study was that we were able to cast such a broad net” to capture conditions, Mr. Bensken said.

Anxiety and mood disorders were originally in separate categories but were grouped together “after recognizing that those who had one pretty much had the other,” he added.

The researchers used a machine learning technique known as association rule mining (ARM) to uncover frequently occurring conditions and combinations of conditions. This same statistical technique is used by companies such as Amazon to determine future purchases based on articles people have bought.

Among 81,963 patients with epilepsy, the most common conditions were anxiety and mood disorders (46.5%). These were followed by hypertension (36.9%), back problems (35.2%), developmental disorders (31.6%), and headache including migraine (29.5%). Urinary tract infections (UTIs) were experienced by 22.8% of the sample.

The rate of anxiety and mood disorders was not unexpected, “but I was surprised to see hypertension so high on the list,” said Mr. Bensken. He noted there is also increasing evidence pointing to a cardiovascular-epilepsy connection.
 

What should neurologists do?

The study also highlights the relatively high rate of back problems, which are not usually considered a comorbidity in patients with epilepsy, Mr. Bensken said. “Back problems likely greatly impact a patient’s quality of life, and seeing them so high on the list makes me wonder if neurologists or epileptologists or primary care doctors are even asking about back pain and how that might impact the ability to function day to day,” he added.

How do these rates compare with the general population? From other studies, the estimated prevalence for anxiety and mood disorders is 20%-30%, compared with almost 50% of the current sample, said Mr. Bensken.

In addition, the rate of hypertension in the study’s epilepsy population was about 7% higher than the general population, and the rate of UTIs was about 12% higher, he reported.

When examining combinations of conditions, anxiety and mood disorders continued to have an “outsized” prevalence, appearing in nearly every combination, the investigators noted.

Almost a quarter (24.7%) of participants had back problems plus anxiety and a mood disorder, and about 15% had headaches and back problems as well as anxiety and a mood disorder.

“That’s a non-negligible amount of the population that have not just one or two things going on but three and four,” said Mr. Bensken.

These new results underscore how complex these patients can be and the need to integrate medical care among different specialties, he noted.

“We don’t believe it’s the neurologist’s job to also manage the hypertension, but being aware of how prevalent hypertension may be and working with the primary care doctor, or at least checking in with the patient and asking if they’re managing their hypertension, is a real priority,” he said.

Researchers also used the ARM system to identify racial disparities, “which have been largely understudied in the epilepsy context,” said Mr. Bensken.

American Indians and Alaskan Natives had a substantially higher prevalence of developmental disabilities, while Black participants had a higher prevalence of hypertension.

One of the study’s themes was that disparities were not uniform, Mr. Bensken noted. “It wasn’t that in every condition the prevalence was lowest for White individuals and highest for everybody else,” he said.

These results point to the need for a larger study to examine the cultural context of these subgroups and such things as structural racism that might drive disparities, he added.

When researchers examined combinations of comorbidities in individuals in the top quartile of hospitalizations and emergency department visits, they found high users had a much higher disease burden, with 75.8% having anxiety or a mood disorder.

The study highlights that patients with epilepsy on Medicaid are “a high priority population,” said Mr. Bensken.
 

 

 

‘Drift down hypothesis’

Commenting on the findings, Fred A. Lado, MD, PhD, director of epilepsy at Northwell Health Eastern and Central Regions, said the increased incidence of comorbidities in patients of low socioeconomic status was not surprising.

“The interesting data here is that we see an even higher incidence among people with epilepsy,” said Dr. Lado, who was not involved with the research.

The study shows how epilepsy exacerbates the effects of low socioeconomic status, he added.

“One of the determinants of socioeconomic status in this case may well be the fact they have seizures and have a limited ability to work and are often more dependent on state assistance and disability support,” Dr. Lado said.

He also referred to the “drift down hypothesis” of chronic disease. “If you have epilepsy and are born into a middle-class family, chances are you will be on disability and can’t work, so you probably have a lower socioeconomic status than your family did as you grew up.”

Dr. Lado noted how “extremely common” mood disorders are in this population and that certain pain syndromes “tracked with those mood disorders.”

“We know mood disorders are more prevalent in people with epilepsy, and now we see that pain-related problems – headache and back pain – are more prevalent in people with epilepsy,” he said.

The data showing “downstream effects of the mood disorders,” from epilepsy to mood disorders to pain disorders, was “very interesting,” Dr. Lado said.

The study was funded by the Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities of the National Institutes of Health. Mr. Bensken has reported receiving research support for this work from the NIH.

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

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Hypertension may double the risk of late-onset epilepsy

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Thu, 12/15/2022 - 15:39

Hypertension is associated with more than a twofold increased risk of developing late-onset epilepsy even in patients who have not had a previous stroke, new research suggests.

After excluding individuals with normal blood pressure who were taking antihypertensive medication, investigators found hypertension was linked to an almost 2.5-fold higher risk of epilepsy.

“Our findings further expand upon our knowledge of the negative effects hypertension has on brain health and, regarding epilepsy, that effect may be starting even in midlife,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University.

“Practicing clinicians should be vigilant to diagnose hypertension, discuss with patients all potential long-term brain health outcomes, and need for treatment. Furthermore, in those presenting with new-onset epilepsy later in life, screening for potentially undiagnosed hypertension should be included in the initial workup,” she said.

The study was published online Nov. 17, 2021, in Epilepsia.
 

Unknown etiology

“New-onset epilepsy risk increases with increasing age over the age of 65 and can affect 15-20 per 1,000 older individuals. Although the most common causes for seizures in this age group are prior history of stroke and presence of dementia, for about 30%-40% of patients, the etiology of seizures remains unknown,” Dr. Stefanidou said.

“We wanted to study if modifiable vascular risk factors that are known to contribute both to vascular brain aging and to neurodegeneration may directly predict the development of epilepsy, even in the absence of clinical stroke or dementia,” she added.

To investigate, the researchers turned to data from participants in the Offspring Cohort of the Framingham Health Study (FHS). The original FHS was an ongoing longitudinal community-based study that first began in 1948. Offspring of the original cohort and their spouses (n = 5,124) were enrolled in the Offspring Cohort in 1971, with surveillance of these second-generation participants based on exam visits occurring every 4 years.

The study included participants who had attended exam 5 (1991-1995), were age 45 years or older, had available vascular risk factor (VRF) data, and available follow-up data on epilepsy status (n = 2,986; mean age, 58 years; 48% male).

The investigators conducted two statistical analyses. In the primary model, they adjusted for age and gender, while in a secondary model they also adjusted for prevalent and interim stroke. They also conducted an analysis that excluded participants treated with antihypertensive medication and had normal blood pressure.
 

Plausible mechanisms

During a mean follow-up of 19.2 years, 55 incident epilepsy cases were identified. The mean age of these patients was 73.8 years.

In the primary model, hypertension was associated with an almost twofold higher risk of developing epilepsy (hazard ratio, 1.97; 95% confidence interval, 1.13-3.45; P = .017).

Interestingly, the Framingham Stroke Risk Profile – a calculation based on an array of factors, including age/sex, systolic blood pressure, antihypertensive therapy, diabetes, history of cardiovascular disease, atrial fibrillation, and cigarette smoking – was not associated with incident epilepsy, and there was no other significant associated between any of the other VRFs when looked at independently.

When the researchers adjusted for prevalent and interim stroke, they continued to find an almost twofold higher risk of developing epilepsy (HR 1.93; 95% CI, 1.10-3.37; P = .022). An analysis that adjusted for competing risk of death obtained similar findings (HR, 1.98; 95% CI, 1.03-3.81; P = .042).

The model that excluded patients receiving antihypertensive treatment, whose blood pressure readings were normal (n = 2,162; 50 incident epilepsy cases) showed an even stronger association (HR, 2.44; 95% CI, 1.36-4.35; P = .003).

“Our results are based on an epidemiological, observational study, therefore our findings point to an association between hypertension and new-onset epilepsy later in life,” said Dr. Stefanidou.

She noted that because it was an observational study, “a cause-effect relationship cannot be established based on these results, but there is growing evidence from our, as well as other, similar cohorts that hypertension, a modifiable vascular risk factor, may indeed be an independent predictor of late-onset epilepsy.”

There are “plausible mechanisms” that support both a direct, and indirect, role of hypertension – for example, through accumulation of small vessel disease in the brain – but further research will be necessary to elucidate the exact mechanisms involved in the process,” she added.
 

 

 

‘Welcome addition’

In a joint comment, Hedley C.A. Emsley, PhD, professor of clinical neuroscience, Lancaster (England) University, and Jasmine Wall, MBBChir, academic clinical fellow in neurology, Lancaster University, described the study as a “welcome addition to this field,” noting that the Framingham Heart Study “lends itself well to an embedded observational study of this nature of late-onset epilepsy.”

Dr. Emsley and Dr. Wall, who were not involved in the research, said that the “apparent magnitude of increased late-onset epilepsy risk association with hypertension in the Stefanidou et al study is quite striking,” even allowing for the “relatively small sample size,” since their analysis and findings appear to “withstand exclusion of individuals who became normotensive on antihypertensive treatment.”

They noted that in recent years there has been a growing body of evidence highlighting the importance of hypertension in late-onset epilepsy epileptogenesis with subclinical cerebrovascular diseases, including “otherwise occult cerebral small vessel disease believed to be a frequent cause.”

The mechanisms “remain unclear,” but they could potentially include diffuse cerebral microangiopathy, structural and physiological changes, and/or blood-brain barrier dysfunction and leakage, they suggested.

“Although there is no current consensus over an age threshold that defines ‘late onset,’ we would argue that age thresholds used in such studies of late-onset epilepsy should be lower, to avoid missing younger adults at risk through vascular mechanisms,” Dr. Emsley and Dr. Wall added.

The study authors suggest that “potential pathophysiologic mechanisms can further be explored in future experimental studies and clinical trials.”

This study was funded by grants from the National Institutes of Health and Finding a Cure for Epilepsy/Seizures. Dr. Stefanidou disclosed relevant financial relationships. Dr. Emsley and Dr. Wall disclosed no relevant financial relationships.

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

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Hypertension is associated with more than a twofold increased risk of developing late-onset epilepsy even in patients who have not had a previous stroke, new research suggests.

After excluding individuals with normal blood pressure who were taking antihypertensive medication, investigators found hypertension was linked to an almost 2.5-fold higher risk of epilepsy.

“Our findings further expand upon our knowledge of the negative effects hypertension has on brain health and, regarding epilepsy, that effect may be starting even in midlife,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University.

“Practicing clinicians should be vigilant to diagnose hypertension, discuss with patients all potential long-term brain health outcomes, and need for treatment. Furthermore, in those presenting with new-onset epilepsy later in life, screening for potentially undiagnosed hypertension should be included in the initial workup,” she said.

The study was published online Nov. 17, 2021, in Epilepsia.
 

Unknown etiology

“New-onset epilepsy risk increases with increasing age over the age of 65 and can affect 15-20 per 1,000 older individuals. Although the most common causes for seizures in this age group are prior history of stroke and presence of dementia, for about 30%-40% of patients, the etiology of seizures remains unknown,” Dr. Stefanidou said.

“We wanted to study if modifiable vascular risk factors that are known to contribute both to vascular brain aging and to neurodegeneration may directly predict the development of epilepsy, even in the absence of clinical stroke or dementia,” she added.

To investigate, the researchers turned to data from participants in the Offspring Cohort of the Framingham Health Study (FHS). The original FHS was an ongoing longitudinal community-based study that first began in 1948. Offspring of the original cohort and their spouses (n = 5,124) were enrolled in the Offspring Cohort in 1971, with surveillance of these second-generation participants based on exam visits occurring every 4 years.

The study included participants who had attended exam 5 (1991-1995), were age 45 years or older, had available vascular risk factor (VRF) data, and available follow-up data on epilepsy status (n = 2,986; mean age, 58 years; 48% male).

The investigators conducted two statistical analyses. In the primary model, they adjusted for age and gender, while in a secondary model they also adjusted for prevalent and interim stroke. They also conducted an analysis that excluded participants treated with antihypertensive medication and had normal blood pressure.
 

Plausible mechanisms

During a mean follow-up of 19.2 years, 55 incident epilepsy cases were identified. The mean age of these patients was 73.8 years.

In the primary model, hypertension was associated with an almost twofold higher risk of developing epilepsy (hazard ratio, 1.97; 95% confidence interval, 1.13-3.45; P = .017).

Interestingly, the Framingham Stroke Risk Profile – a calculation based on an array of factors, including age/sex, systolic blood pressure, antihypertensive therapy, diabetes, history of cardiovascular disease, atrial fibrillation, and cigarette smoking – was not associated with incident epilepsy, and there was no other significant associated between any of the other VRFs when looked at independently.

When the researchers adjusted for prevalent and interim stroke, they continued to find an almost twofold higher risk of developing epilepsy (HR 1.93; 95% CI, 1.10-3.37; P = .022). An analysis that adjusted for competing risk of death obtained similar findings (HR, 1.98; 95% CI, 1.03-3.81; P = .042).

The model that excluded patients receiving antihypertensive treatment, whose blood pressure readings were normal (n = 2,162; 50 incident epilepsy cases) showed an even stronger association (HR, 2.44; 95% CI, 1.36-4.35; P = .003).

“Our results are based on an epidemiological, observational study, therefore our findings point to an association between hypertension and new-onset epilepsy later in life,” said Dr. Stefanidou.

She noted that because it was an observational study, “a cause-effect relationship cannot be established based on these results, but there is growing evidence from our, as well as other, similar cohorts that hypertension, a modifiable vascular risk factor, may indeed be an independent predictor of late-onset epilepsy.”

There are “plausible mechanisms” that support both a direct, and indirect, role of hypertension – for example, through accumulation of small vessel disease in the brain – but further research will be necessary to elucidate the exact mechanisms involved in the process,” she added.
 

 

 

‘Welcome addition’

In a joint comment, Hedley C.A. Emsley, PhD, professor of clinical neuroscience, Lancaster (England) University, and Jasmine Wall, MBBChir, academic clinical fellow in neurology, Lancaster University, described the study as a “welcome addition to this field,” noting that the Framingham Heart Study “lends itself well to an embedded observational study of this nature of late-onset epilepsy.”

Dr. Emsley and Dr. Wall, who were not involved in the research, said that the “apparent magnitude of increased late-onset epilepsy risk association with hypertension in the Stefanidou et al study is quite striking,” even allowing for the “relatively small sample size,” since their analysis and findings appear to “withstand exclusion of individuals who became normotensive on antihypertensive treatment.”

They noted that in recent years there has been a growing body of evidence highlighting the importance of hypertension in late-onset epilepsy epileptogenesis with subclinical cerebrovascular diseases, including “otherwise occult cerebral small vessel disease believed to be a frequent cause.”

The mechanisms “remain unclear,” but they could potentially include diffuse cerebral microangiopathy, structural and physiological changes, and/or blood-brain barrier dysfunction and leakage, they suggested.

“Although there is no current consensus over an age threshold that defines ‘late onset,’ we would argue that age thresholds used in such studies of late-onset epilepsy should be lower, to avoid missing younger adults at risk through vascular mechanisms,” Dr. Emsley and Dr. Wall added.

The study authors suggest that “potential pathophysiologic mechanisms can further be explored in future experimental studies and clinical trials.”

This study was funded by grants from the National Institutes of Health and Finding a Cure for Epilepsy/Seizures. Dr. Stefanidou disclosed relevant financial relationships. Dr. Emsley and Dr. Wall disclosed no relevant financial relationships.

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

Hypertension is associated with more than a twofold increased risk of developing late-onset epilepsy even in patients who have not had a previous stroke, new research suggests.

After excluding individuals with normal blood pressure who were taking antihypertensive medication, investigators found hypertension was linked to an almost 2.5-fold higher risk of epilepsy.

“Our findings further expand upon our knowledge of the negative effects hypertension has on brain health and, regarding epilepsy, that effect may be starting even in midlife,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University.

“Practicing clinicians should be vigilant to diagnose hypertension, discuss with patients all potential long-term brain health outcomes, and need for treatment. Furthermore, in those presenting with new-onset epilepsy later in life, screening for potentially undiagnosed hypertension should be included in the initial workup,” she said.

The study was published online Nov. 17, 2021, in Epilepsia.
 

Unknown etiology

“New-onset epilepsy risk increases with increasing age over the age of 65 and can affect 15-20 per 1,000 older individuals. Although the most common causes for seizures in this age group are prior history of stroke and presence of dementia, for about 30%-40% of patients, the etiology of seizures remains unknown,” Dr. Stefanidou said.

“We wanted to study if modifiable vascular risk factors that are known to contribute both to vascular brain aging and to neurodegeneration may directly predict the development of epilepsy, even in the absence of clinical stroke or dementia,” she added.

To investigate, the researchers turned to data from participants in the Offspring Cohort of the Framingham Health Study (FHS). The original FHS was an ongoing longitudinal community-based study that first began in 1948. Offspring of the original cohort and their spouses (n = 5,124) were enrolled in the Offspring Cohort in 1971, with surveillance of these second-generation participants based on exam visits occurring every 4 years.

The study included participants who had attended exam 5 (1991-1995), were age 45 years or older, had available vascular risk factor (VRF) data, and available follow-up data on epilepsy status (n = 2,986; mean age, 58 years; 48% male).

The investigators conducted two statistical analyses. In the primary model, they adjusted for age and gender, while in a secondary model they also adjusted for prevalent and interim stroke. They also conducted an analysis that excluded participants treated with antihypertensive medication and had normal blood pressure.
 

Plausible mechanisms

During a mean follow-up of 19.2 years, 55 incident epilepsy cases were identified. The mean age of these patients was 73.8 years.

In the primary model, hypertension was associated with an almost twofold higher risk of developing epilepsy (hazard ratio, 1.97; 95% confidence interval, 1.13-3.45; P = .017).

Interestingly, the Framingham Stroke Risk Profile – a calculation based on an array of factors, including age/sex, systolic blood pressure, antihypertensive therapy, diabetes, history of cardiovascular disease, atrial fibrillation, and cigarette smoking – was not associated with incident epilepsy, and there was no other significant associated between any of the other VRFs when looked at independently.

When the researchers adjusted for prevalent and interim stroke, they continued to find an almost twofold higher risk of developing epilepsy (HR 1.93; 95% CI, 1.10-3.37; P = .022). An analysis that adjusted for competing risk of death obtained similar findings (HR, 1.98; 95% CI, 1.03-3.81; P = .042).

The model that excluded patients receiving antihypertensive treatment, whose blood pressure readings were normal (n = 2,162; 50 incident epilepsy cases) showed an even stronger association (HR, 2.44; 95% CI, 1.36-4.35; P = .003).

“Our results are based on an epidemiological, observational study, therefore our findings point to an association between hypertension and new-onset epilepsy later in life,” said Dr. Stefanidou.

She noted that because it was an observational study, “a cause-effect relationship cannot be established based on these results, but there is growing evidence from our, as well as other, similar cohorts that hypertension, a modifiable vascular risk factor, may indeed be an independent predictor of late-onset epilepsy.”

There are “plausible mechanisms” that support both a direct, and indirect, role of hypertension – for example, through accumulation of small vessel disease in the brain – but further research will be necessary to elucidate the exact mechanisms involved in the process,” she added.
 

 

 

‘Welcome addition’

In a joint comment, Hedley C.A. Emsley, PhD, professor of clinical neuroscience, Lancaster (England) University, and Jasmine Wall, MBBChir, academic clinical fellow in neurology, Lancaster University, described the study as a “welcome addition to this field,” noting that the Framingham Heart Study “lends itself well to an embedded observational study of this nature of late-onset epilepsy.”

Dr. Emsley and Dr. Wall, who were not involved in the research, said that the “apparent magnitude of increased late-onset epilepsy risk association with hypertension in the Stefanidou et al study is quite striking,” even allowing for the “relatively small sample size,” since their analysis and findings appear to “withstand exclusion of individuals who became normotensive on antihypertensive treatment.”

They noted that in recent years there has been a growing body of evidence highlighting the importance of hypertension in late-onset epilepsy epileptogenesis with subclinical cerebrovascular diseases, including “otherwise occult cerebral small vessel disease believed to be a frequent cause.”

The mechanisms “remain unclear,” but they could potentially include diffuse cerebral microangiopathy, structural and physiological changes, and/or blood-brain barrier dysfunction and leakage, they suggested.

“Although there is no current consensus over an age threshold that defines ‘late onset,’ we would argue that age thresholds used in such studies of late-onset epilepsy should be lower, to avoid missing younger adults at risk through vascular mechanisms,” Dr. Emsley and Dr. Wall added.

The study authors suggest that “potential pathophysiologic mechanisms can further be explored in future experimental studies and clinical trials.”

This study was funded by grants from the National Institutes of Health and Finding a Cure for Epilepsy/Seizures. Dr. Stefanidou disclosed relevant financial relationships. Dr. Emsley and Dr. Wall disclosed no relevant financial relationships.

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

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Managing simple febrile seizures without lumbar puncture safe: 15-year study

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Most children with simple febrile seizures (SFSs) can be safely managed without lumbar puncture or other diagnostic tests without risking delayed diagnosis of bacterial meningitis, new data gathered from a 15-year span suggest.

Vidya R. Raghavan, MD, with the division of emergency medicine at Boston Children’s Hospital and Harvard Medical School, also in Boston, published their findings in Pediatrics.

In 2011, researchers published the American Academy of Pediatrics simple febrile seizure guideline, which recommends limiting lumbar puncture to non–low-risk patients. The guidelines also specified that neuroimaging and hematologic testing are not routinely recommended.

Dr. Raghavan and coauthors studied evaluation and management trends of the patients before and after the guidelines. They identified 142,121 children diagnosed with SFS who presented to 1 of 49 pediatric tertiary EDs and met other study criteria. Changes in management of SFS had started years before the guideline and positive effects continued after the guideline publication.

Researchers found a significant 95% decline in rates of lumbar puncture between 2005 and 2019 from 11.6% (95% confidence interval, 10.8%-12.4%) of children in 2005 to 0.6% (95% CI, 0.5%-0.8%; P < .001) in 2019. The most significant declines were among infants 6 months to 1 year.

“We found similar declines in rates of diagnostic laboratory and radiologic testing, intravenous antibiotic administration, hospitalization, and costs,” the authors wrote.

“Importantly,” they wrote, “the decrease in testing was not associated with a concurrent increase in delayed diagnoses of bacterial meningitis.”

The number of hospital admissions and total costs also dropped significantly over the 15-year span of the study. After adjusting for inflation, the authors wrote, costs dropped from an average $1,523 in 2005 to $605 (P < .001) in 2019.

Among first-time presentations for SFSs, 19.2% (95% CI, 18.3%-20.2%) resulted in admission in 2005. That rate dropped to 5.2% (95% CI, 4.8%-5.6%) in 2019 (P < .001), although the authors noted that trend largely plateaued after the guideline was published.

“Our findings are consistent with smaller studies published before 2011 in which researchers found declining rates of LP [lumbar puncture] in children presenting to the ED with their first SFS,” the authors wrote.

Dr. Mercedes Blackstone

Mercedes Blackstone, MD, an emergency physician at the Children’s Hospital of Philadelphia, said in an interview that the paper offers reassurance for changed practice over the last decade.

She said there was substantial relief in pediatrics when the 2011 guidelines recognized formally that protocols were outdated, especially as bacterial meningitis had become increasingly rare with widespread use of pneumococcal and Haemophilus influenzae vaccines. Practitioners had already started to limit the spinal taps on their own.

“We were not really complying with the prior recommendation to do a spinal tap in all those children because it often felt like doing a pretty invasive procedure with a very low yield in what was often a very well child in front of you,” she said.

In 2007, the authors noted, a few years before the guidelines, rates of bacterial meningitis had decreased to 7 per 100,000 in children aged between 2 and 23 months and 0.56 per 100,000 in children aged between 2 and 10 years.

However, Dr. Blackstone said, there was still a worry among some practitioners that there could be missed cases of bacterial meningitis.

“It’s very helpful to see that in all those years, the guidelines have been very validated and there were really no missed cases,” said Dr. Blackstone, author of CHOP’s febrile seizures clinical pathway.

It was good to see the number of CT scans drop as well, she said. Dr. Raghavan’s team found they decreased from 10.6% to 1.6%; P < .001, over the study period.

“Earlier work had shown that there was still a fair amount of head CTs happening and that’s radiation to the young brain,” Dr. Blackstone noted. “This is great news.”

Dr. Blackstone said it was great to see so many children from so many children’s hospitals included in the study.

The paper confirmed that “we’ve reduced a lot of unnecessary testing, saved a lot of cost, and had no increased risk to the patients,” she said.

Dr. Blackstone pointed out that the authors include a limitation that many children are seen in nonpediatric centers in community adult ED and she said those settings tend to have more testing.

“Hopefully, these guidelines have penetrated into the whole community,” she said. “With this paper they should feel reassured that they can spare children some of these tests and procedures.”

Dr. Raghavan and Dr. Blackstone declared no relevant financial relationships.

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Most children with simple febrile seizures (SFSs) can be safely managed without lumbar puncture or other diagnostic tests without risking delayed diagnosis of bacterial meningitis, new data gathered from a 15-year span suggest.

Vidya R. Raghavan, MD, with the division of emergency medicine at Boston Children’s Hospital and Harvard Medical School, also in Boston, published their findings in Pediatrics.

In 2011, researchers published the American Academy of Pediatrics simple febrile seizure guideline, which recommends limiting lumbar puncture to non–low-risk patients. The guidelines also specified that neuroimaging and hematologic testing are not routinely recommended.

Dr. Raghavan and coauthors studied evaluation and management trends of the patients before and after the guidelines. They identified 142,121 children diagnosed with SFS who presented to 1 of 49 pediatric tertiary EDs and met other study criteria. Changes in management of SFS had started years before the guideline and positive effects continued after the guideline publication.

Researchers found a significant 95% decline in rates of lumbar puncture between 2005 and 2019 from 11.6% (95% confidence interval, 10.8%-12.4%) of children in 2005 to 0.6% (95% CI, 0.5%-0.8%; P < .001) in 2019. The most significant declines were among infants 6 months to 1 year.

“We found similar declines in rates of diagnostic laboratory and radiologic testing, intravenous antibiotic administration, hospitalization, and costs,” the authors wrote.

“Importantly,” they wrote, “the decrease in testing was not associated with a concurrent increase in delayed diagnoses of bacterial meningitis.”

The number of hospital admissions and total costs also dropped significantly over the 15-year span of the study. After adjusting for inflation, the authors wrote, costs dropped from an average $1,523 in 2005 to $605 (P < .001) in 2019.

Among first-time presentations for SFSs, 19.2% (95% CI, 18.3%-20.2%) resulted in admission in 2005. That rate dropped to 5.2% (95% CI, 4.8%-5.6%) in 2019 (P < .001), although the authors noted that trend largely plateaued after the guideline was published.

“Our findings are consistent with smaller studies published before 2011 in which researchers found declining rates of LP [lumbar puncture] in children presenting to the ED with their first SFS,” the authors wrote.

Dr. Mercedes Blackstone

Mercedes Blackstone, MD, an emergency physician at the Children’s Hospital of Philadelphia, said in an interview that the paper offers reassurance for changed practice over the last decade.

She said there was substantial relief in pediatrics when the 2011 guidelines recognized formally that protocols were outdated, especially as bacterial meningitis had become increasingly rare with widespread use of pneumococcal and Haemophilus influenzae vaccines. Practitioners had already started to limit the spinal taps on their own.

“We were not really complying with the prior recommendation to do a spinal tap in all those children because it often felt like doing a pretty invasive procedure with a very low yield in what was often a very well child in front of you,” she said.

In 2007, the authors noted, a few years before the guidelines, rates of bacterial meningitis had decreased to 7 per 100,000 in children aged between 2 and 23 months and 0.56 per 100,000 in children aged between 2 and 10 years.

However, Dr. Blackstone said, there was still a worry among some practitioners that there could be missed cases of bacterial meningitis.

“It’s very helpful to see that in all those years, the guidelines have been very validated and there were really no missed cases,” said Dr. Blackstone, author of CHOP’s febrile seizures clinical pathway.

It was good to see the number of CT scans drop as well, she said. Dr. Raghavan’s team found they decreased from 10.6% to 1.6%; P < .001, over the study period.

“Earlier work had shown that there was still a fair amount of head CTs happening and that’s radiation to the young brain,” Dr. Blackstone noted. “This is great news.”

Dr. Blackstone said it was great to see so many children from so many children’s hospitals included in the study.

The paper confirmed that “we’ve reduced a lot of unnecessary testing, saved a lot of cost, and had no increased risk to the patients,” she said.

Dr. Blackstone pointed out that the authors include a limitation that many children are seen in nonpediatric centers in community adult ED and she said those settings tend to have more testing.

“Hopefully, these guidelines have penetrated into the whole community,” she said. “With this paper they should feel reassured that they can spare children some of these tests and procedures.”

Dr. Raghavan and Dr. Blackstone declared no relevant financial relationships.

 

Most children with simple febrile seizures (SFSs) can be safely managed without lumbar puncture or other diagnostic tests without risking delayed diagnosis of bacterial meningitis, new data gathered from a 15-year span suggest.

Vidya R. Raghavan, MD, with the division of emergency medicine at Boston Children’s Hospital and Harvard Medical School, also in Boston, published their findings in Pediatrics.

In 2011, researchers published the American Academy of Pediatrics simple febrile seizure guideline, which recommends limiting lumbar puncture to non–low-risk patients. The guidelines also specified that neuroimaging and hematologic testing are not routinely recommended.

Dr. Raghavan and coauthors studied evaluation and management trends of the patients before and after the guidelines. They identified 142,121 children diagnosed with SFS who presented to 1 of 49 pediatric tertiary EDs and met other study criteria. Changes in management of SFS had started years before the guideline and positive effects continued after the guideline publication.

Researchers found a significant 95% decline in rates of lumbar puncture between 2005 and 2019 from 11.6% (95% confidence interval, 10.8%-12.4%) of children in 2005 to 0.6% (95% CI, 0.5%-0.8%; P < .001) in 2019. The most significant declines were among infants 6 months to 1 year.

“We found similar declines in rates of diagnostic laboratory and radiologic testing, intravenous antibiotic administration, hospitalization, and costs,” the authors wrote.

“Importantly,” they wrote, “the decrease in testing was not associated with a concurrent increase in delayed diagnoses of bacterial meningitis.”

The number of hospital admissions and total costs also dropped significantly over the 15-year span of the study. After adjusting for inflation, the authors wrote, costs dropped from an average $1,523 in 2005 to $605 (P < .001) in 2019.

Among first-time presentations for SFSs, 19.2% (95% CI, 18.3%-20.2%) resulted in admission in 2005. That rate dropped to 5.2% (95% CI, 4.8%-5.6%) in 2019 (P < .001), although the authors noted that trend largely plateaued after the guideline was published.

“Our findings are consistent with smaller studies published before 2011 in which researchers found declining rates of LP [lumbar puncture] in children presenting to the ED with their first SFS,” the authors wrote.

Dr. Mercedes Blackstone

Mercedes Blackstone, MD, an emergency physician at the Children’s Hospital of Philadelphia, said in an interview that the paper offers reassurance for changed practice over the last decade.

She said there was substantial relief in pediatrics when the 2011 guidelines recognized formally that protocols were outdated, especially as bacterial meningitis had become increasingly rare with widespread use of pneumococcal and Haemophilus influenzae vaccines. Practitioners had already started to limit the spinal taps on their own.

“We were not really complying with the prior recommendation to do a spinal tap in all those children because it often felt like doing a pretty invasive procedure with a very low yield in what was often a very well child in front of you,” she said.

In 2007, the authors noted, a few years before the guidelines, rates of bacterial meningitis had decreased to 7 per 100,000 in children aged between 2 and 23 months and 0.56 per 100,000 in children aged between 2 and 10 years.

However, Dr. Blackstone said, there was still a worry among some practitioners that there could be missed cases of bacterial meningitis.

“It’s very helpful to see that in all those years, the guidelines have been very validated and there were really no missed cases,” said Dr. Blackstone, author of CHOP’s febrile seizures clinical pathway.

It was good to see the number of CT scans drop as well, she said. Dr. Raghavan’s team found they decreased from 10.6% to 1.6%; P < .001, over the study period.

“Earlier work had shown that there was still a fair amount of head CTs happening and that’s radiation to the young brain,” Dr. Blackstone noted. “This is great news.”

Dr. Blackstone said it was great to see so many children from so many children’s hospitals included in the study.

The paper confirmed that “we’ve reduced a lot of unnecessary testing, saved a lot of cost, and had no increased risk to the patients,” she said.

Dr. Blackstone pointed out that the authors include a limitation that many children are seen in nonpediatric centers in community adult ED and she said those settings tend to have more testing.

“Hopefully, these guidelines have penetrated into the whole community,” she said. “With this paper they should feel reassured that they can spare children some of these tests and procedures.”

Dr. Raghavan and Dr. Blackstone declared no relevant financial relationships.

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Antiepileptic medications linked to increased priapism risk

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Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.

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After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.

These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.

“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.

If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

Noteworthy limitations

Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.

She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.

These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”

Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.

Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
 

Replication needed

Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.

Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.

They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.

The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.

A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.

The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.

“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
 

 

 

New and important hypothesis?

Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”

He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.

However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.

He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.

It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.

“If a seemingly dangerous symptom would be happening as a result of one of these medications, it is quite surprising that it has not been noticed sooner,” he said.

Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”

The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.

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

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Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.

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After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.

These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.

“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.

If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

Noteworthy limitations

Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.

She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.

These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”

Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.

Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
 

Replication needed

Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.

Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.

They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.

The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.

A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.

The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.

“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
 

 

 

New and important hypothesis?

Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”

He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.

However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.

He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.

It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.

“If a seemingly dangerous symptom would be happening as a result of one of these medications, it is quite surprising that it has not been noticed sooner,” he said.

Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”

The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.

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

Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.

©Thinkstock

After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.

These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.

“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.

If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

Noteworthy limitations

Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.

She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.

These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”

Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.

Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
 

Replication needed

Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.

Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.

They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.

The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.

A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.

The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.

“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
 

 

 

New and important hypothesis?

Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”

He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.

However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.

He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.

It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.

“If a seemingly dangerous symptom would be happening as a result of one of these medications, it is quite surprising that it has not been noticed sooner,” he said.

Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”

The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.

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

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Epidiolex plus THC lowers seizures in pediatric epilepsy

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Wed, 10/13/2021 - 11:55

Children and young adults with epilepsy had fewer seizures after combination treatment with the drug Epidiolex, which contains the cannabidiol (CBD), and various doses of tetrahydrocannabinol (THC), the component of cannabis that makes people high in larger quantities, researchers reported.

“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.

In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.

CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.

Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.

When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
 

Combination therapy

For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.

The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).

Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.

The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
 

Still controversial

Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”

However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.

For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”

University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”

But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”

As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”

No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
 

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Children and young adults with epilepsy had fewer seizures after combination treatment with the drug Epidiolex, which contains the cannabidiol (CBD), and various doses of tetrahydrocannabinol (THC), the component of cannabis that makes people high in larger quantities, researchers reported.

“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.

In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.

CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.

Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.

When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
 

Combination therapy

For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.

The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).

Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.

The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
 

Still controversial

Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”

However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.

For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”

University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”

But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”

As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”

No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
 

Children and young adults with epilepsy had fewer seizures after combination treatment with the drug Epidiolex, which contains the cannabidiol (CBD), and various doses of tetrahydrocannabinol (THC), the component of cannabis that makes people high in larger quantities, researchers reported.

“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.

In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.

CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.

Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.

When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
 

Combination therapy

For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.

The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).

Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.

The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
 

Still controversial

Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”

However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.

For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”

University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”

But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”

As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”

No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
 

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Double antiglutamatergic therapy is ‘promising’ for super-refractory status epilepticus

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Sustained, intensive therapy with two antiglutamatergic drugs is superior to standard aggressive treatment for postanoxic super-refractory status epilepticus (SRSE), new research suggests.

In a retrospective cohort study of survivors of cardiac arrest with postanoxic sustained SRSE, resolution of the condition was achieved by 81% of those who received intensive treatment of ketamine plus perampanel, versus 41% of those who received standard care.

The novelty of the new treatment approach is the duration of therapy as well as the dual antiglutamate drugs, researchers note.

“So the logic is to continue treatment until resolution of refractory status epilepticus under continuous EEG [electroencephalographic] monitoring,” reported lead investigator Simone Beretta, MD, San Gerardo University Hospital, Monza, Italy.

Therapy was guided by data on brainstem reflexes, N20 cortical responses, neuronal serum enolase levels, and neuroimaging.

If all or most of these indicators are favorable, “we continue to treat without any time limit,” Dr. Beretta said. However, if the indicators become unfavorable, clinicians should consider lowering the intensity of care, he added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

SUPER-CAT trial

In SRSE, epileptic seizures occur one after another without patients recovering consciousness in between. Standard aggressive therapy for the condition does not include antiglutamatergic drugs, the researchers noted.

In the Super-Refractory Status Epilepticus After Cardiac Arrest: Aggressive Treatment Guided by Multimodal Prognostic Indicators (SUPER-CAT) study, researchers assessed the combination of two such medications.

The first was the anti-NMDA receptor drug ketamine, which was given by intravenous bolus and then continuous infusion for 3 days guided by continuous EEG to reach a ketamine EEG pattern, as evidenced by alpha and beta waves. It was combined with the anti-AMPA receptor antiepileptic perampanel via nasogastric tube for 5 days, followed by slow tapering.

Dr. Beretta noted that in the ongoing TELSTAR trial, which involved a similar patient population, a different drug combination is being used. A major difference between the two trials is that in the TELSTAR trial, aggressive therapy continues for only 2 days if there is no response.

“In the SUPER-CAT study, we continue far beyond 2 days in the majority of patients,” he said. In addition, ketamine and perampanel were not assessed in TELSTAR.

In SUPER-CAT, 489 survivors of cardiac arrest were recruited over 10 years. Of these, 101 had refractory status epilepticus. After excluding those with more than two indicators of poor prognosis (n = 31) or whose status epilepticus resolved (n = 14), 56 patients were determined to have SRSE. All had experienced relapse after undergoing one cycle of anesthetic.

The 56 participants received one of three treatment regimens: double antiglutamate (DAG) therapy of ketamine and perampanel (n = 26), single antiglutamate therapy with either agent (n = 8), or aggressive nonantiglutamate (NAG) therapy with antiepilepsy drugs and anesthetics other than ketamine or perampanel (n = 22).

The single-antiglutamate group was not included in the analysis of patient outcomes.

The DAG and NAG groups were well balanced at baseline. There were no significant differences in median age (60 years vs. 66 years), gender, low cerebral blood flow, presence of bilateral pupillary or corneal reflexes, neuron-specific enolase levels, cortical N20 somatosenory evoked potentials, moderate to severe postanoxic brain injury, and hypothermia/targeted temperature management.
 

 

 

Primary outcome met

More patients in the DAG group (42%) had moderate to severe postanoxic brain injury than in the NAG group (28%). However, the difference was not statistically significant (P = .08), possibly because of the small sample sizes. The number of antiepileptic drugs and the number of cycles of anesthetics did not differ between the groups.

Results showed that efficacy and safety outcomes favored DAG therapy.

The primary efficacy outcome was resolution of status epilepticus within 3 days after initiation of treatments. Status epilepticus resolved for 21 of 26 patients in the DAG group (81%), versus 9 of 22 patients in the NAG group (41%; odds ratio, 6.06; 95% confidence interval, 1.66-22.12; P = .005).

For secondary efficacy outcomes, there was a trend in favor of DAG, but differences from the NAG group were not statistically significant. In the groups, 46% versus 32% awakened and responded to commands before discharge from the intensive care unit, and 32% versus 23% showed good neurologic outcome at 6 months.

The primary safety outcome of all-cause mortality risk in the ICU was 90% lower for patients treated with DAG than for those treated with NAG (15% vs. 64%; OR, 0.1; 95% CI, 0.02-0.41; P < .01). Dr. Beretta explained that the high mortality rate in the NAG group was presumably a result of unresolved status epilepticus.

The secondary safety outcome of a transitory rise of gamma-glutamyl transferase greater than three times the upper limit of normal in the DAG group was expected with high-dose perampanel, the investigators noted. This outcome occurred in 77% of the DAG group versus 27% of the NAG group (OR, 9.88; 95% CI, 2.4-32.9; P < .001).

There was no statistically significant difference in incidence of recurrent cardiac arrest during therapy. This occurred in one member of the DAG group and in none in the NAG group.

Dr. Beretta reported that their investigations are still in a retrospective phase, but the researchers plan to move the work into a prospective phase and possibly a randomized trial soon.
 

Fascinating, promising

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center, Columbus, said the study provides “fascinating, very helpful data” about a condition that has responded well to current treatment options.

He added that his center has used “the innovative treatments” discussed in the study for a few patients.

“More concrete evidence will push us to use it more uniformly across all our patient population [that] has refractory status. So I’m very optimistic, and the data were very promising,” said Dr. Singh, who was not involved with the research.

He cautioned that the study was retrospective, not randomized or controlled, and that it involved a small number of patients but said that the data were “heading in the right direction.”

Although resolution of status epilepticus was better among patients in the DAG group than in the NAG group, the awakenings and neurologic outcomes were “pretty much same as standard medical therapy, which we commonly give to our patients,” said Dr. Singh. “We see this phenomenon all the time in our patients.”

He noted that other factors can determine how patients respond, such as conditions of the heart or kidneys, the presence of sepsis, and multiorgan dysfunction. These factors were not controlled for in the study.

Nonetheless, he said the study achieved its primary endpoint of better resolution of status epilepticus “because that’s the first thing you want to see: whether the treatment is taking care of that.”

The study received no outside funding. Dr. Beretta and Dr. Singh have disclosed no relevant financial relationships.

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

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Sustained, intensive therapy with two antiglutamatergic drugs is superior to standard aggressive treatment for postanoxic super-refractory status epilepticus (SRSE), new research suggests.

In a retrospective cohort study of survivors of cardiac arrest with postanoxic sustained SRSE, resolution of the condition was achieved by 81% of those who received intensive treatment of ketamine plus perampanel, versus 41% of those who received standard care.

The novelty of the new treatment approach is the duration of therapy as well as the dual antiglutamate drugs, researchers note.

“So the logic is to continue treatment until resolution of refractory status epilepticus under continuous EEG [electroencephalographic] monitoring,” reported lead investigator Simone Beretta, MD, San Gerardo University Hospital, Monza, Italy.

Therapy was guided by data on brainstem reflexes, N20 cortical responses, neuronal serum enolase levels, and neuroimaging.

If all or most of these indicators are favorable, “we continue to treat without any time limit,” Dr. Beretta said. However, if the indicators become unfavorable, clinicians should consider lowering the intensity of care, he added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

SUPER-CAT trial

In SRSE, epileptic seizures occur one after another without patients recovering consciousness in between. Standard aggressive therapy for the condition does not include antiglutamatergic drugs, the researchers noted.

In the Super-Refractory Status Epilepticus After Cardiac Arrest: Aggressive Treatment Guided by Multimodal Prognostic Indicators (SUPER-CAT) study, researchers assessed the combination of two such medications.

The first was the anti-NMDA receptor drug ketamine, which was given by intravenous bolus and then continuous infusion for 3 days guided by continuous EEG to reach a ketamine EEG pattern, as evidenced by alpha and beta waves. It was combined with the anti-AMPA receptor antiepileptic perampanel via nasogastric tube for 5 days, followed by slow tapering.

Dr. Beretta noted that in the ongoing TELSTAR trial, which involved a similar patient population, a different drug combination is being used. A major difference between the two trials is that in the TELSTAR trial, aggressive therapy continues for only 2 days if there is no response.

“In the SUPER-CAT study, we continue far beyond 2 days in the majority of patients,” he said. In addition, ketamine and perampanel were not assessed in TELSTAR.

In SUPER-CAT, 489 survivors of cardiac arrest were recruited over 10 years. Of these, 101 had refractory status epilepticus. After excluding those with more than two indicators of poor prognosis (n = 31) or whose status epilepticus resolved (n = 14), 56 patients were determined to have SRSE. All had experienced relapse after undergoing one cycle of anesthetic.

The 56 participants received one of three treatment regimens: double antiglutamate (DAG) therapy of ketamine and perampanel (n = 26), single antiglutamate therapy with either agent (n = 8), or aggressive nonantiglutamate (NAG) therapy with antiepilepsy drugs and anesthetics other than ketamine or perampanel (n = 22).

The single-antiglutamate group was not included in the analysis of patient outcomes.

The DAG and NAG groups were well balanced at baseline. There were no significant differences in median age (60 years vs. 66 years), gender, low cerebral blood flow, presence of bilateral pupillary or corneal reflexes, neuron-specific enolase levels, cortical N20 somatosenory evoked potentials, moderate to severe postanoxic brain injury, and hypothermia/targeted temperature management.
 

 

 

Primary outcome met

More patients in the DAG group (42%) had moderate to severe postanoxic brain injury than in the NAG group (28%). However, the difference was not statistically significant (P = .08), possibly because of the small sample sizes. The number of antiepileptic drugs and the number of cycles of anesthetics did not differ between the groups.

Results showed that efficacy and safety outcomes favored DAG therapy.

The primary efficacy outcome was resolution of status epilepticus within 3 days after initiation of treatments. Status epilepticus resolved for 21 of 26 patients in the DAG group (81%), versus 9 of 22 patients in the NAG group (41%; odds ratio, 6.06; 95% confidence interval, 1.66-22.12; P = .005).

For secondary efficacy outcomes, there was a trend in favor of DAG, but differences from the NAG group were not statistically significant. In the groups, 46% versus 32% awakened and responded to commands before discharge from the intensive care unit, and 32% versus 23% showed good neurologic outcome at 6 months.

The primary safety outcome of all-cause mortality risk in the ICU was 90% lower for patients treated with DAG than for those treated with NAG (15% vs. 64%; OR, 0.1; 95% CI, 0.02-0.41; P < .01). Dr. Beretta explained that the high mortality rate in the NAG group was presumably a result of unresolved status epilepticus.

The secondary safety outcome of a transitory rise of gamma-glutamyl transferase greater than three times the upper limit of normal in the DAG group was expected with high-dose perampanel, the investigators noted. This outcome occurred in 77% of the DAG group versus 27% of the NAG group (OR, 9.88; 95% CI, 2.4-32.9; P < .001).

There was no statistically significant difference in incidence of recurrent cardiac arrest during therapy. This occurred in one member of the DAG group and in none in the NAG group.

Dr. Beretta reported that their investigations are still in a retrospective phase, but the researchers plan to move the work into a prospective phase and possibly a randomized trial soon.
 

Fascinating, promising

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center, Columbus, said the study provides “fascinating, very helpful data” about a condition that has responded well to current treatment options.

He added that his center has used “the innovative treatments” discussed in the study for a few patients.

“More concrete evidence will push us to use it more uniformly across all our patient population [that] has refractory status. So I’m very optimistic, and the data were very promising,” said Dr. Singh, who was not involved with the research.

He cautioned that the study was retrospective, not randomized or controlled, and that it involved a small number of patients but said that the data were “heading in the right direction.”

Although resolution of status epilepticus was better among patients in the DAG group than in the NAG group, the awakenings and neurologic outcomes were “pretty much same as standard medical therapy, which we commonly give to our patients,” said Dr. Singh. “We see this phenomenon all the time in our patients.”

He noted that other factors can determine how patients respond, such as conditions of the heart or kidneys, the presence of sepsis, and multiorgan dysfunction. These factors were not controlled for in the study.

Nonetheless, he said the study achieved its primary endpoint of better resolution of status epilepticus “because that’s the first thing you want to see: whether the treatment is taking care of that.”

The study received no outside funding. Dr. Beretta and Dr. Singh have disclosed no relevant financial relationships.

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

Sustained, intensive therapy with two antiglutamatergic drugs is superior to standard aggressive treatment for postanoxic super-refractory status epilepticus (SRSE), new research suggests.

In a retrospective cohort study of survivors of cardiac arrest with postanoxic sustained SRSE, resolution of the condition was achieved by 81% of those who received intensive treatment of ketamine plus perampanel, versus 41% of those who received standard care.

The novelty of the new treatment approach is the duration of therapy as well as the dual antiglutamate drugs, researchers note.

“So the logic is to continue treatment until resolution of refractory status epilepticus under continuous EEG [electroencephalographic] monitoring,” reported lead investigator Simone Beretta, MD, San Gerardo University Hospital, Monza, Italy.

Therapy was guided by data on brainstem reflexes, N20 cortical responses, neuronal serum enolase levels, and neuroimaging.

If all or most of these indicators are favorable, “we continue to treat without any time limit,” Dr. Beretta said. However, if the indicators become unfavorable, clinicians should consider lowering the intensity of care, he added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

SUPER-CAT trial

In SRSE, epileptic seizures occur one after another without patients recovering consciousness in between. Standard aggressive therapy for the condition does not include antiglutamatergic drugs, the researchers noted.

In the Super-Refractory Status Epilepticus After Cardiac Arrest: Aggressive Treatment Guided by Multimodal Prognostic Indicators (SUPER-CAT) study, researchers assessed the combination of two such medications.

The first was the anti-NMDA receptor drug ketamine, which was given by intravenous bolus and then continuous infusion for 3 days guided by continuous EEG to reach a ketamine EEG pattern, as evidenced by alpha and beta waves. It was combined with the anti-AMPA receptor antiepileptic perampanel via nasogastric tube for 5 days, followed by slow tapering.

Dr. Beretta noted that in the ongoing TELSTAR trial, which involved a similar patient population, a different drug combination is being used. A major difference between the two trials is that in the TELSTAR trial, aggressive therapy continues for only 2 days if there is no response.

“In the SUPER-CAT study, we continue far beyond 2 days in the majority of patients,” he said. In addition, ketamine and perampanel were not assessed in TELSTAR.

In SUPER-CAT, 489 survivors of cardiac arrest were recruited over 10 years. Of these, 101 had refractory status epilepticus. After excluding those with more than two indicators of poor prognosis (n = 31) or whose status epilepticus resolved (n = 14), 56 patients were determined to have SRSE. All had experienced relapse after undergoing one cycle of anesthetic.

The 56 participants received one of three treatment regimens: double antiglutamate (DAG) therapy of ketamine and perampanel (n = 26), single antiglutamate therapy with either agent (n = 8), or aggressive nonantiglutamate (NAG) therapy with antiepilepsy drugs and anesthetics other than ketamine or perampanel (n = 22).

The single-antiglutamate group was not included in the analysis of patient outcomes.

The DAG and NAG groups were well balanced at baseline. There were no significant differences in median age (60 years vs. 66 years), gender, low cerebral blood flow, presence of bilateral pupillary or corneal reflexes, neuron-specific enolase levels, cortical N20 somatosenory evoked potentials, moderate to severe postanoxic brain injury, and hypothermia/targeted temperature management.
 

 

 

Primary outcome met

More patients in the DAG group (42%) had moderate to severe postanoxic brain injury than in the NAG group (28%). However, the difference was not statistically significant (P = .08), possibly because of the small sample sizes. The number of antiepileptic drugs and the number of cycles of anesthetics did not differ between the groups.

Results showed that efficacy and safety outcomes favored DAG therapy.

The primary efficacy outcome was resolution of status epilepticus within 3 days after initiation of treatments. Status epilepticus resolved for 21 of 26 patients in the DAG group (81%), versus 9 of 22 patients in the NAG group (41%; odds ratio, 6.06; 95% confidence interval, 1.66-22.12; P = .005).

For secondary efficacy outcomes, there was a trend in favor of DAG, but differences from the NAG group were not statistically significant. In the groups, 46% versus 32% awakened and responded to commands before discharge from the intensive care unit, and 32% versus 23% showed good neurologic outcome at 6 months.

The primary safety outcome of all-cause mortality risk in the ICU was 90% lower for patients treated with DAG than for those treated with NAG (15% vs. 64%; OR, 0.1; 95% CI, 0.02-0.41; P < .01). Dr. Beretta explained that the high mortality rate in the NAG group was presumably a result of unresolved status epilepticus.

The secondary safety outcome of a transitory rise of gamma-glutamyl transferase greater than three times the upper limit of normal in the DAG group was expected with high-dose perampanel, the investigators noted. This outcome occurred in 77% of the DAG group versus 27% of the NAG group (OR, 9.88; 95% CI, 2.4-32.9; P < .001).

There was no statistically significant difference in incidence of recurrent cardiac arrest during therapy. This occurred in one member of the DAG group and in none in the NAG group.

Dr. Beretta reported that their investigations are still in a retrospective phase, but the researchers plan to move the work into a prospective phase and possibly a randomized trial soon.
 

Fascinating, promising

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center, Columbus, said the study provides “fascinating, very helpful data” about a condition that has responded well to current treatment options.

He added that his center has used “the innovative treatments” discussed in the study for a few patients.

“More concrete evidence will push us to use it more uniformly across all our patient population [that] has refractory status. So I’m very optimistic, and the data were very promising,” said Dr. Singh, who was not involved with the research.

He cautioned that the study was retrospective, not randomized or controlled, and that it involved a small number of patients but said that the data were “heading in the right direction.”

Although resolution of status epilepticus was better among patients in the DAG group than in the NAG group, the awakenings and neurologic outcomes were “pretty much same as standard medical therapy, which we commonly give to our patients,” said Dr. Singh. “We see this phenomenon all the time in our patients.”

He noted that other factors can determine how patients respond, such as conditions of the heart or kidneys, the presence of sepsis, and multiorgan dysfunction. These factors were not controlled for in the study.

Nonetheless, he said the study achieved its primary endpoint of better resolution of status epilepticus “because that’s the first thing you want to see: whether the treatment is taking care of that.”

The study received no outside funding. Dr. Beretta and Dr. Singh have disclosed no relevant financial relationships.

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

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Is genetic testing valuable in the clinical management of epilepsy?

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Mon, 11/01/2021 - 14:55

Genetic testing in patients with epilepsy can yield useful information that informs treatment and improves seizure control and other outcomes, new research shows.

Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.

“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

Test results can be practice-changing

Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.

A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.

The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.

She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.



“Of the physicians who changed treatment, 75% reported there were positive outcomes for the patients,” Dr. McKnight told meeting attendees. “Most common was a reduction or a complete elimination of seizures, and that was reported in 65% of the cases.”

In many cases, the changes resulted in clinical improvements.

“There were 64 individuals who were having daily seizures before the genetic testing,” Dr. McKnight reported via email. “After receiving the genetic diagnosis and modifying their treatment, their physicians reported that 26% of individuals had complete seizure control and 46% of individuals had reduced seizure frequency to either weekly (20%), monthly (20%) or annually (6%).”



The best seizure control after modifying disease management occurred among children. Although the changes were not as dramatic for adults, they trended toward lower seizure frequency.

“It is still pretty significant that adults can receive genetic testing later in life and still have benefit in controlling their seizures,” Dr. McKnight said.

Twenty-three percent of patients showed improvement in behavior, development, academics, or movement issues, while 6% experienced reduced medication side effects.

Dr. McKnight also explored reasons for physicians not making changes to clinical management of patients based on the genetic results. The most common reason was that management was already consistent with the results (47.3%), followed by the results not being informative (26.1%), the results possibly being useful for future treatments in development (19.0%), or other or unknown reasons (7.6%).

Besides direct health and quality of life benefits from better seizure control, Dr. McKnight cited previous economic studies showing lower health care costs.

“It looked like an individual who has good seizure control will incur about 14,000 U.S. dollars a year compared with an individual with pretty poor seizure control, where it can be closer to 23,000 U.S. dollars a year,” Dr. McKnight said. This is mainly attributed to reduced hospitalizations and emergency department visits.

Dr. McKnight noted that currently there is no cost of genetic testing to the patient, the hospital, or insurers. Pharmaceutical companies, she said, sponsor the testing to potentially gather patients for clinical drug trials in development. However, patients remain completely anonymous.

Physicians who wish to have patient samples tested agree that the companies may contact them to ask if any of their patients with positive genetic test results would like to participate in a trial.

Dr. McKnight noted that genetic testing can be considered actionable in the clinic, helping to guide clinical decision-making and potentially leading to better outcomes. Going forward, she suggested performing large case-controlled studies “of individuals with the same genetic etiology ... to really find a true causation or correlation.”

 

 

Growing influence of genetic testing

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.

He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.

“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.

He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.

For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.

Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.

Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.

Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.

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

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Neurology Reviews - 29(11)
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Genetic testing in patients with epilepsy can yield useful information that informs treatment and improves seizure control and other outcomes, new research shows.

Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.

“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

Test results can be practice-changing

Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.

A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.

The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.

She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.



“Of the physicians who changed treatment, 75% reported there were positive outcomes for the patients,” Dr. McKnight told meeting attendees. “Most common was a reduction or a complete elimination of seizures, and that was reported in 65% of the cases.”

In many cases, the changes resulted in clinical improvements.

“There were 64 individuals who were having daily seizures before the genetic testing,” Dr. McKnight reported via email. “After receiving the genetic diagnosis and modifying their treatment, their physicians reported that 26% of individuals had complete seizure control and 46% of individuals had reduced seizure frequency to either weekly (20%), monthly (20%) or annually (6%).”



The best seizure control after modifying disease management occurred among children. Although the changes were not as dramatic for adults, they trended toward lower seizure frequency.

“It is still pretty significant that adults can receive genetic testing later in life and still have benefit in controlling their seizures,” Dr. McKnight said.

Twenty-three percent of patients showed improvement in behavior, development, academics, or movement issues, while 6% experienced reduced medication side effects.

Dr. McKnight also explored reasons for physicians not making changes to clinical management of patients based on the genetic results. The most common reason was that management was already consistent with the results (47.3%), followed by the results not being informative (26.1%), the results possibly being useful for future treatments in development (19.0%), or other or unknown reasons (7.6%).

Besides direct health and quality of life benefits from better seizure control, Dr. McKnight cited previous economic studies showing lower health care costs.

“It looked like an individual who has good seizure control will incur about 14,000 U.S. dollars a year compared with an individual with pretty poor seizure control, where it can be closer to 23,000 U.S. dollars a year,” Dr. McKnight said. This is mainly attributed to reduced hospitalizations and emergency department visits.

Dr. McKnight noted that currently there is no cost of genetic testing to the patient, the hospital, or insurers. Pharmaceutical companies, she said, sponsor the testing to potentially gather patients for clinical drug trials in development. However, patients remain completely anonymous.

Physicians who wish to have patient samples tested agree that the companies may contact them to ask if any of their patients with positive genetic test results would like to participate in a trial.

Dr. McKnight noted that genetic testing can be considered actionable in the clinic, helping to guide clinical decision-making and potentially leading to better outcomes. Going forward, she suggested performing large case-controlled studies “of individuals with the same genetic etiology ... to really find a true causation or correlation.”

 

 

Growing influence of genetic testing

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.

He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.

“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.

He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.

For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.

Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.

Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.

Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.

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

Genetic testing in patients with epilepsy can yield useful information that informs treatment and improves seizure control and other outcomes, new research shows.

Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.

“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

Test results can be practice-changing

Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.

A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.

The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.

She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.



“Of the physicians who changed treatment, 75% reported there were positive outcomes for the patients,” Dr. McKnight told meeting attendees. “Most common was a reduction or a complete elimination of seizures, and that was reported in 65% of the cases.”

In many cases, the changes resulted in clinical improvements.

“There were 64 individuals who were having daily seizures before the genetic testing,” Dr. McKnight reported via email. “After receiving the genetic diagnosis and modifying their treatment, their physicians reported that 26% of individuals had complete seizure control and 46% of individuals had reduced seizure frequency to either weekly (20%), monthly (20%) or annually (6%).”



The best seizure control after modifying disease management occurred among children. Although the changes were not as dramatic for adults, they trended toward lower seizure frequency.

“It is still pretty significant that adults can receive genetic testing later in life and still have benefit in controlling their seizures,” Dr. McKnight said.

Twenty-three percent of patients showed improvement in behavior, development, academics, or movement issues, while 6% experienced reduced medication side effects.

Dr. McKnight also explored reasons for physicians not making changes to clinical management of patients based on the genetic results. The most common reason was that management was already consistent with the results (47.3%), followed by the results not being informative (26.1%), the results possibly being useful for future treatments in development (19.0%), or other or unknown reasons (7.6%).

Besides direct health and quality of life benefits from better seizure control, Dr. McKnight cited previous economic studies showing lower health care costs.

“It looked like an individual who has good seizure control will incur about 14,000 U.S. dollars a year compared with an individual with pretty poor seizure control, where it can be closer to 23,000 U.S. dollars a year,” Dr. McKnight said. This is mainly attributed to reduced hospitalizations and emergency department visits.

Dr. McKnight noted that currently there is no cost of genetic testing to the patient, the hospital, or insurers. Pharmaceutical companies, she said, sponsor the testing to potentially gather patients for clinical drug trials in development. However, patients remain completely anonymous.

Physicians who wish to have patient samples tested agree that the companies may contact them to ask if any of their patients with positive genetic test results would like to participate in a trial.

Dr. McKnight noted that genetic testing can be considered actionable in the clinic, helping to guide clinical decision-making and potentially leading to better outcomes. Going forward, she suggested performing large case-controlled studies “of individuals with the same genetic etiology ... to really find a true causation or correlation.”

 

 

Growing influence of genetic testing

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.

He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.

“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.

He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.

For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.

Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.

Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.

Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.

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

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Neurology Reviews - 29(11)
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