Epilepsy & Seizures

In 2022, the Journal of Neurosurgery took the unusual step of publishing a case report of a nonhuman subject, in this case an 8-year-old male sea lion named Cronutt, who had severe epilepsy that in many ways mirrored the common form seen in humans.

A 2020 xenotransplantation of interneuron progenitor cells in the sea lion’s hippocampus may have cured him. “He’s doing fantastic,” said Scott Baraban, PhD, a professor of neurological surgery at the University of California San Francisco Weill Institute for Neurosciences. The procedure offered a confirmation of success stories in mice and could serve as a bridge to human studies, although the science remains murky. 

Cronutt’s story began the first time he was found stranded along the California coast in San Luis Obispo County, in November 2017, lethargic and disoriented. Nevertheless, he improved quickly under the care of the Marine Mammal Rescue Center in Sausalito, California, and they released him back into the wild 2 weeks later. Unfortunately, his troubles weren’t over. In the next 2 months, he came to the attention of the rehabilitation center two more times, and the resulting habituation to humans meant that he could not be re-released to the wild.

Things only got worse from there. He experienced a convulsive seizure and loss of consciousness in early 2018 and another seizure a year later. Despite anti-seizure medication, the episodes continued, and eventually, he stopped eating for long periods and lost a quarter of his body weight. It looked like euthanasia was the only alternative.

 

Neurosurgeons Take Notice

Baraban has devoted his career to animal models of epilepsy, focusing mainly on mice. He developed a method to transplant GABAergic interneurons from pigs, which can pick up the inhibitory role of endogenous neurons. In epileptic mice, mouse-derived progenitor cells mature into inhibitory synapses and dampen seizures, and even reverse behavioral problems. 

Baraban was intrigued by the potential of the procedure to help sea lions and potentially bridge the gap between murine and human studies, and he was eager to try the approach after he learned of Cronutt’s case through his colleague Paul Buckmaster at Stanford University, California, who had collaborated with the Marine Mammal Rescue Center to demonstrate that sea lions suffer hippocampal damage that is very similar to human temporal lobe epilepsy.

It turns out that surgery on a sea lion is more complicated than on a mouse. The surgeon needs to conduct an MRI scan to locate the lesion and guide the placement of transplanted cells, and the big animals need to be sedated and intubated. Their caretakers are not enthusiastic about invasive procedures, but Cronutt had already been imaged as part of an earlier study of the effects of exposure to domoic acid on the sea lion brain, giving neurosurgeons at UCSF the information they needed.

In 2020, they transplanted GABAergic interneurons into Cronutt’s hippocampus in a last-ditch effort to save his life. He improved rapidly, and his caregivers eventually tapered off his anti-seizure medications. Today, Cronutt is living seizure-free at the Six Flags Discovery Kingdom in Vallejo, California. He even began participating in shows at Six Flags. “He is able to learn things and do things cognitively that he couldn’t do before,” said Baraban.

The researchers have not followed up with more imaging. “We just haven’t had any reason to bother him. It’s very invasive to get him to an MRI center,” said Baraban.

There haven’t been any more procedures on sea lions, in part because sea lions at rescue centers must be returned to the wild within 6-8 months, and animals with pig-based progenitor cells can’t be released. Any sea lion that would undergo such a procedure would have to live permanently in captivity, potentially for 20-30 years. “It’s a huge undertaking and expense,” said Baraban. There are also logistical challenges with the need to have MRI and other facilities close at hand to where the sea lion is kept.

 

Human Connections

As a veterinarian interested in human epilepsy, Buckmaster sought to find additional animal models for human temporal lobe epilepsy. He later met a veterinarian who worked with the Marine Mammal Center, who told him about temporal lobe epilepsy in sea lions. 

Cronutt was just one of hundreds of California sea lions and other mammals rendered helpless by epileptic seizures induced by exposure to domoic acid, a chemical released by toxic algal blooms. Sea otters, whales, and even birds can likewise be affected. Humans, too, though it is rare: A domoic acid poisoning event in mussels from Prince Edward Island led to convulsions and an eventual diagnosis of temporal lobe epilepsy in an 84-year-old Canadian man, and three others died.

Most of Buckmaster’s work had been done in rats, but seizures are different than what are seen in humans. The damage isn’t unilateral, as in human epilepsy. The damage is unilateral in sea lions, and they suffer damage to similar neurons to those injured in humans. “In rats, you don’t see much loss of granule cells, which are the main neuron in the dentate gyrus, a region that’s really affected in temporal lobe epilepsy. In people, there’s a lot of variation, but [on average] you lose about half your granule cells, and that’s similar to sea lions. In rats, they just don’t lose them,” said Buckmaster.

That makes sea lions a useful model, but they hardly crack the case of human epilepsy. “To be humble about it, we don’t really know what’s causing the seizures. We have an idea of what region of the brain the seizures are coming from, but in terms of the cellular mechanisms, it’s still not clear,” said Buckmaster.

He also noted that, unlike sea lions, the vast majority of patients with human epilepsy have no exposure to domoic acid. That said, the case of sea lions and other marine animals makes researchers wonder. “This is speculative, but a lot of people with temporal epilepsy will have a history of some kind of precipitating event. Typically, it’s earlier in life, and a common one is prolonged febrile seizures. That could be a link to the domoic acid exposure in sea lions because the domoic acid exposure in sea lions frequently causes prolonged seizures. If the seizures are severe enough and long enough, they cause permanent brain damage, and that can cause temporal lobe epilepsy. That’s what we strongly believe is causing the temporal lobe epilepsy in sea lions. Prolonged, severe seizures can be caused by many things other than domoic acid, and that could be what causes it in many cases of human temporal lobe epilepsy,” said Buckmaster.

The approach taken with Cronutt makes sense to Buckmaster, who was not directly involved in the procedure. “The ideal treatment would be something that you would administer once, and it would cause cessation of seizures without any side effects. The transplantation of inhibitory cells is a treatment that would last and hopefully wouldn’t have any side effects and hopefully would provide complete control of seizures. It’s unlikely to reach all those goals, but it’s a step in the right direction, hopefully,” said Buckmaster.

He noted that Cronutt is only a single case and not proof that the procedure will work more generally. It’s possible the sea lion would have improved on his own without treatment, and the procedure itself could have influenced the brain. “That’s been the case with other neurological conditions that have attempted to be treated with cell transplantation,” said Buckmaster.

A phase 1/2 clinical trial, sponsored by Neurona Therapeutics, is currently recruiting patients to test transplant of human interneurons created from pluripotent stem cells into both temporal lobes of patients with drug-resistant bilateral mesial temporal lobe epilepsy.

 

Cronutt’s Course

Although he has improved dramatically, it’s possible that Cronutt continues to experience nonconvulsive seizures, which would not be easy to detect in an animal. “You don’t know if Cronutt’s seizures are controlled or not unless you can look at the electrical activity in Cronutt’s brain, and to my knowledge that has not been done,” said Buckmaster.

Previous studies in rats did repeatedly demonstrate the potential of the treatment approach. Despite the feel-good story of Cronutt, “that’s probably the most compelling evidence in support of that arm of treatment,” said Buckmaster.

Buckmaster and Barbaran had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

In 2022, the Journal of Neurosurgery took the unusual step of publishing a case report of a nonhuman subject, in this case an 8-year-old male sea lion named Cronutt, who had severe epilepsy that in many ways mirrored the common form seen in humans.

A 2020 xenotransplantation of interneuron progenitor cells in the sea lion’s hippocampus may have cured him. “He’s doing fantastic,” said Scott Baraban, PhD, a professor of neurological surgery at the University of California San Francisco Weill Institute for Neurosciences. The procedure offered a confirmation of success stories in mice and could serve as a bridge to human studies, although the science remains murky. 

Cronutt’s story began the first time he was found stranded along the California coast in San Luis Obispo County, in November 2017, lethargic and disoriented. Nevertheless, he improved quickly under the care of the Marine Mammal Rescue Center in Sausalito, California, and they released him back into the wild 2 weeks later. Unfortunately, his troubles weren’t over. In the next 2 months, he came to the attention of the rehabilitation center two more times, and the resulting habituation to humans meant that he could not be re-released to the wild.

Things only got worse from there. He experienced a convulsive seizure and loss of consciousness in early 2018 and another seizure a year later. Despite anti-seizure medication, the episodes continued, and eventually, he stopped eating for long periods and lost a quarter of his body weight. It looked like euthanasia was the only alternative.

 

Neurosurgeons Take Notice

Baraban has devoted his career to animal models of epilepsy, focusing mainly on mice. He developed a method to transplant GABAergic interneurons from pigs, which can pick up the inhibitory role of endogenous neurons. In epileptic mice, mouse-derived progenitor cells mature into inhibitory synapses and dampen seizures, and even reverse behavioral problems. 

Baraban was intrigued by the potential of the procedure to help sea lions and potentially bridge the gap between murine and human studies, and he was eager to try the approach after he learned of Cronutt’s case through his colleague Paul Buckmaster at Stanford University, California, who had collaborated with the Marine Mammal Rescue Center to demonstrate that sea lions suffer hippocampal damage that is very similar to human temporal lobe epilepsy.

It turns out that surgery on a sea lion is more complicated than on a mouse. The surgeon needs to conduct an MRI scan to locate the lesion and guide the placement of transplanted cells, and the big animals need to be sedated and intubated. Their caretakers are not enthusiastic about invasive procedures, but Cronutt had already been imaged as part of an earlier study of the effects of exposure to domoic acid on the sea lion brain, giving neurosurgeons at UCSF the information they needed.

In 2020, they transplanted GABAergic interneurons into Cronutt’s hippocampus in a last-ditch effort to save his life. He improved rapidly, and his caregivers eventually tapered off his anti-seizure medications. Today, Cronutt is living seizure-free at the Six Flags Discovery Kingdom in Vallejo, California. He even began participating in shows at Six Flags. “He is able to learn things and do things cognitively that he couldn’t do before,” said Baraban.

The researchers have not followed up with more imaging. “We just haven’t had any reason to bother him. It’s very invasive to get him to an MRI center,” said Baraban.

There haven’t been any more procedures on sea lions, in part because sea lions at rescue centers must be returned to the wild within 6-8 months, and animals with pig-based progenitor cells can’t be released. Any sea lion that would undergo such a procedure would have to live permanently in captivity, potentially for 20-30 years. “It’s a huge undertaking and expense,” said Baraban. There are also logistical challenges with the need to have MRI and other facilities close at hand to where the sea lion is kept.

 

Human Connections

As a veterinarian interested in human epilepsy, Buckmaster sought to find additional animal models for human temporal lobe epilepsy. He later met a veterinarian who worked with the Marine Mammal Center, who told him about temporal lobe epilepsy in sea lions. 

Cronutt was just one of hundreds of California sea lions and other mammals rendered helpless by epileptic seizures induced by exposure to domoic acid, a chemical released by toxic algal blooms. Sea otters, whales, and even birds can likewise be affected. Humans, too, though it is rare: A domoic acid poisoning event in mussels from Prince Edward Island led to convulsions and an eventual diagnosis of temporal lobe epilepsy in an 84-year-old Canadian man, and three others died.

Most of Buckmaster’s work had been done in rats, but seizures are different than what are seen in humans. The damage isn’t unilateral, as in human epilepsy. The damage is unilateral in sea lions, and they suffer damage to similar neurons to those injured in humans. “In rats, you don’t see much loss of granule cells, which are the main neuron in the dentate gyrus, a region that’s really affected in temporal lobe epilepsy. In people, there’s a lot of variation, but [on average] you lose about half your granule cells, and that’s similar to sea lions. In rats, they just don’t lose them,” said Buckmaster.

That makes sea lions a useful model, but they hardly crack the case of human epilepsy. “To be humble about it, we don’t really know what’s causing the seizures. We have an idea of what region of the brain the seizures are coming from, but in terms of the cellular mechanisms, it’s still not clear,” said Buckmaster.

He also noted that, unlike sea lions, the vast majority of patients with human epilepsy have no exposure to domoic acid. That said, the case of sea lions and other marine animals makes researchers wonder. “This is speculative, but a lot of people with temporal epilepsy will have a history of some kind of precipitating event. Typically, it’s earlier in life, and a common one is prolonged febrile seizures. That could be a link to the domoic acid exposure in sea lions because the domoic acid exposure in sea lions frequently causes prolonged seizures. If the seizures are severe enough and long enough, they cause permanent brain damage, and that can cause temporal lobe epilepsy. That’s what we strongly believe is causing the temporal lobe epilepsy in sea lions. Prolonged, severe seizures can be caused by many things other than domoic acid, and that could be what causes it in many cases of human temporal lobe epilepsy,” said Buckmaster.

The approach taken with Cronutt makes sense to Buckmaster, who was not directly involved in the procedure. “The ideal treatment would be something that you would administer once, and it would cause cessation of seizures without any side effects. The transplantation of inhibitory cells is a treatment that would last and hopefully wouldn’t have any side effects and hopefully would provide complete control of seizures. It’s unlikely to reach all those goals, but it’s a step in the right direction, hopefully,” said Buckmaster.

He noted that Cronutt is only a single case and not proof that the procedure will work more generally. It’s possible the sea lion would have improved on his own without treatment, and the procedure itself could have influenced the brain. “That’s been the case with other neurological conditions that have attempted to be treated with cell transplantation,” said Buckmaster.

A phase 1/2 clinical trial, sponsored by Neurona Therapeutics, is currently recruiting patients to test transplant of human interneurons created from pluripotent stem cells into both temporal lobes of patients with drug-resistant bilateral mesial temporal lobe epilepsy.

 

Cronutt’s Course

Although he has improved dramatically, it’s possible that Cronutt continues to experience nonconvulsive seizures, which would not be easy to detect in an animal. “You don’t know if Cronutt’s seizures are controlled or not unless you can look at the electrical activity in Cronutt’s brain, and to my knowledge that has not been done,” said Buckmaster.

Previous studies in rats did repeatedly demonstrate the potential of the treatment approach. Despite the feel-good story of Cronutt, “that’s probably the most compelling evidence in support of that arm of treatment,” said Buckmaster.

Buckmaster and Barbaran had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

In 2022, the Journal of Neurosurgery took the unusual step of publishing a case report of a nonhuman subject, in this case an 8-year-old male sea lion named Cronutt, who had severe epilepsy that in many ways mirrored the common form seen in humans.

A 2020 xenotransplantation of interneuron progenitor cells in the sea lion’s hippocampus may have cured him. “He’s doing fantastic,” said Scott Baraban, PhD, a professor of neurological surgery at the University of California San Francisco Weill Institute for Neurosciences. The procedure offered a confirmation of success stories in mice and could serve as a bridge to human studies, although the science remains murky. 

Cronutt’s story began the first time he was found stranded along the California coast in San Luis Obispo County, in November 2017, lethargic and disoriented. Nevertheless, he improved quickly under the care of the Marine Mammal Rescue Center in Sausalito, California, and they released him back into the wild 2 weeks later. Unfortunately, his troubles weren’t over. In the next 2 months, he came to the attention of the rehabilitation center two more times, and the resulting habituation to humans meant that he could not be re-released to the wild.

Things only got worse from there. He experienced a convulsive seizure and loss of consciousness in early 2018 and another seizure a year later. Despite anti-seizure medication, the episodes continued, and eventually, he stopped eating for long periods and lost a quarter of his body weight. It looked like euthanasia was the only alternative.

 

Neurosurgeons Take Notice

Baraban has devoted his career to animal models of epilepsy, focusing mainly on mice. He developed a method to transplant GABAergic interneurons from pigs, which can pick up the inhibitory role of endogenous neurons. In epileptic mice, mouse-derived progenitor cells mature into inhibitory synapses and dampen seizures, and even reverse behavioral problems. 

Baraban was intrigued by the potential of the procedure to help sea lions and potentially bridge the gap between murine and human studies, and he was eager to try the approach after he learned of Cronutt’s case through his colleague Paul Buckmaster at Stanford University, California, who had collaborated with the Marine Mammal Rescue Center to demonstrate that sea lions suffer hippocampal damage that is very similar to human temporal lobe epilepsy.

It turns out that surgery on a sea lion is more complicated than on a mouse. The surgeon needs to conduct an MRI scan to locate the lesion and guide the placement of transplanted cells, and the big animals need to be sedated and intubated. Their caretakers are not enthusiastic about invasive procedures, but Cronutt had already been imaged as part of an earlier study of the effects of exposure to domoic acid on the sea lion brain, giving neurosurgeons at UCSF the information they needed.

In 2020, they transplanted GABAergic interneurons into Cronutt’s hippocampus in a last-ditch effort to save his life. He improved rapidly, and his caregivers eventually tapered off his anti-seizure medications. Today, Cronutt is living seizure-free at the Six Flags Discovery Kingdom in Vallejo, California. He even began participating in shows at Six Flags. “He is able to learn things and do things cognitively that he couldn’t do before,” said Baraban.

The researchers have not followed up with more imaging. “We just haven’t had any reason to bother him. It’s very invasive to get him to an MRI center,” said Baraban.

There haven’t been any more procedures on sea lions, in part because sea lions at rescue centers must be returned to the wild within 6-8 months, and animals with pig-based progenitor cells can’t be released. Any sea lion that would undergo such a procedure would have to live permanently in captivity, potentially for 20-30 years. “It’s a huge undertaking and expense,” said Baraban. There are also logistical challenges with the need to have MRI and other facilities close at hand to where the sea lion is kept.

 

Human Connections

As a veterinarian interested in human epilepsy, Buckmaster sought to find additional animal models for human temporal lobe epilepsy. He later met a veterinarian who worked with the Marine Mammal Center, who told him about temporal lobe epilepsy in sea lions. 

Cronutt was just one of hundreds of California sea lions and other mammals rendered helpless by epileptic seizures induced by exposure to domoic acid, a chemical released by toxic algal blooms. Sea otters, whales, and even birds can likewise be affected. Humans, too, though it is rare: A domoic acid poisoning event in mussels from Prince Edward Island led to convulsions and an eventual diagnosis of temporal lobe epilepsy in an 84-year-old Canadian man, and three others died.

Most of Buckmaster’s work had been done in rats, but seizures are different than what are seen in humans. The damage isn’t unilateral, as in human epilepsy. The damage is unilateral in sea lions, and they suffer damage to similar neurons to those injured in humans. “In rats, you don’t see much loss of granule cells, which are the main neuron in the dentate gyrus, a region that’s really affected in temporal lobe epilepsy. In people, there’s a lot of variation, but [on average] you lose about half your granule cells, and that’s similar to sea lions. In rats, they just don’t lose them,” said Buckmaster.

That makes sea lions a useful model, but they hardly crack the case of human epilepsy. “To be humble about it, we don’t really know what’s causing the seizures. We have an idea of what region of the brain the seizures are coming from, but in terms of the cellular mechanisms, it’s still not clear,” said Buckmaster.

He also noted that, unlike sea lions, the vast majority of patients with human epilepsy have no exposure to domoic acid. That said, the case of sea lions and other marine animals makes researchers wonder. “This is speculative, but a lot of people with temporal epilepsy will have a history of some kind of precipitating event. Typically, it’s earlier in life, and a common one is prolonged febrile seizures. That could be a link to the domoic acid exposure in sea lions because the domoic acid exposure in sea lions frequently causes prolonged seizures. If the seizures are severe enough and long enough, they cause permanent brain damage, and that can cause temporal lobe epilepsy. That’s what we strongly believe is causing the temporal lobe epilepsy in sea lions. Prolonged, severe seizures can be caused by many things other than domoic acid, and that could be what causes it in many cases of human temporal lobe epilepsy,” said Buckmaster.

The approach taken with Cronutt makes sense to Buckmaster, who was not directly involved in the procedure. “The ideal treatment would be something that you would administer once, and it would cause cessation of seizures without any side effects. The transplantation of inhibitory cells is a treatment that would last and hopefully wouldn’t have any side effects and hopefully would provide complete control of seizures. It’s unlikely to reach all those goals, but it’s a step in the right direction, hopefully,” said Buckmaster.

He noted that Cronutt is only a single case and not proof that the procedure will work more generally. It’s possible the sea lion would have improved on his own without treatment, and the procedure itself could have influenced the brain. “That’s been the case with other neurological conditions that have attempted to be treated with cell transplantation,” said Buckmaster.

A phase 1/2 clinical trial, sponsored by Neurona Therapeutics, is currently recruiting patients to test transplant of human interneurons created from pluripotent stem cells into both temporal lobes of patients with drug-resistant bilateral mesial temporal lobe epilepsy.

 

Cronutt’s Course

Although he has improved dramatically, it’s possible that Cronutt continues to experience nonconvulsive seizures, which would not be easy to detect in an animal. “You don’t know if Cronutt’s seizures are controlled or not unless you can look at the electrical activity in Cronutt’s brain, and to my knowledge that has not been done,” said Buckmaster.

Previous studies in rats did repeatedly demonstrate the potential of the treatment approach. Despite the feel-good story of Cronutt, “that’s probably the most compelling evidence in support of that arm of treatment,” said Buckmaster.

Buckmaster and Barbaran had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Gestational hypertension, preeclampsia, or eclampsia is associated with a significantly higher risk for neurologic disorders such as migraine or epilepsy in the years following a first pregnancy, new research suggests.

The risk was highest in those with gestational eclampsia, who had a 70% increased chance of developing a neurologic disorder, including a fivefold increased risk for epilepsy, investigators found.

“When consulting women with new-onset neurological disorders, it’s important to inquire about their pregnancy history, as pregnancy complications such as gestational hypertension, preeclampsia, and eclampsia have been associated with an increased risk of neurological disorders later in life.” Therese Friis, MD, PhD student, Department of Women’s and Children’s Health, Uppsala University in Sweden, said in an interview.

The findings were published online in JAMA Neurology.

Most studies of maternal outcomes after gestational hypertension, preeclampsia, or eclampsia have focused on long-term risks for cardiovascular disease or neurologic complications such as stroke, dementia, and cognitive impairment. And many of these studies were relatively small and based on interviews or questionnaires.

“We wanted to investigate whether women with a hypertensive disorder of pregnancy also had a risk of other neurological complications, closer in time to the pregnancy,” said Friis.

The new study included 648,385 women (mean age, 28.5 years) whose first pregnancy occurred between 2005 and 2018. Of these, 94% had a normotensive pregnancy, 2% had gestational hypertension, 4% had preeclampsia without eclampsia, and 0.1% had eclampsia.

Gestational hypertension was defined as new-onset systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg; preeclampsia was defined as gestational hypertension accompanied by proteinuria; and eclampsia was defined as tonic-clonic seizures without other etiology accompanied by preeclampsia.

Researchers used linked Swedish national registries that collect data on pregnancies, births, and infant and maternal characteristics. Among other things, they controlled for maternal age, early pregnancy body mass index, education level, and pregestational and gestational diabetes.

The primary outcome was a composite of five new-onset neurologic diagnoses: Migraine, headache, epilepsy, sleep disorder, and mental fatigue (neurasthenia), although one diagnosis was sufficient, from 42 days to 15 years after childbirth. Mean follow-up was 7.7 years.

 

Fivefold Epilepsy Risk

Compared with normotensive pregnancies, the risk for the primary outcome was 70% greater in those with eclampsia (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.16-2.50), 27% higher for gestational hypertension (aHR, 1.27; 95% CI, 1.12-1.45), and 32% for preeclampsia (aHR, 1.32; 95% CI, 1.22-1.42).

Researchers also looked at the risk for individual neurologic disorders. There were too few neurasthenia events to generate meaningful results, so this diagnosis was omitted from the analysis.

Here, the study found women with eclampsia had five times the risk for epilepsy (aHR, 5.31; 95% CI, 2.85-9.89) compared with women with normotensive pregnancies.

The underlying mechanism for this association is unclear. However, said Friis, eclampsia and epilepsy share common pathways, such as neuroinflammation, and women with epilepsy before pregnancy run an increased risk for eclampsia.

“So common underlying pathways might increase the risk both for eclampsia in cases of a seizure disorder and a future seizure disorder after eclampsia,” she said.

In addition, preeclampsia and, in particular, eclampsia can cause irreversible subclinical cerebral infarcts found in areas of cerebral edema, she added. “These infarcts or scarring of brain tissue could potentially serve as foci for later epileptic activity.”

Researchers separated women with preeclampsia (with or without eclampsia) into those with preterm (less than 37 weeks; 21%) and term (79%) deliveries. As Friis explained, women with preterm preeclampsia have a higher risk for acute complications and long-term cardiovascular outcomes than those with term preeclampsia.

Compared with those with normotensive pregnancies, investigators found an increased risk for the composite neurologic outcome among women with preterm preeclampsia (aHR, 1.54; 95% CI, 1.34-1.79), but also for those with term preeclampsia (aHR, 1.27; 95% CI, 1.17-1.38).

 

Common Vascular Component

The study also showed gestational hypertension and preeclampsia were associated with a later diagnosis of migraine, suggesting a possible common underlying vascular component.

“The increased risk of migraine following preeclampsia could be linked to endothelial damage at the blood-brain barrier level and alterations in cerebral blood flow and arterial vasospasm found in eclampsia, but this is only speculation,” said Friis.

The analysis also found an association between preeclampsia and a later diagnosis of headache. But this result likely encompasses several headache diagnoses, including migraine, so “it’s challenging to draw conclusions about the underlying mechanisms,” Friis added.

The study didn’t consider diagnoses from primary healthcare, which resulted in relatively few outcomes. The authors explained they could only identify the most severe cases; for example, women referred to specialized care.

Another potential study limitation is that Swedish registers don’t include information on race or ethnicity. Evidence shows there are racial differences in the risk for cardiovascular outcomes after preeclampsia.

This area of research is important as most women will experience at least one pregnancy in their lifetime, and preeclampsia affects 3%-5% of pregnancies. Further research is needed to understand the underlying pathophysiological mechanisms and the long-term consequences of this disorder, said Friis.

She added she hopes more therapeutic options will be available in the future for neuroprotective treatment for women with gestational hypertensive disorders.

Asked to comment, Thomas Vidic, MD, clinical professor of neurology, Indiana University School of Medicine, South Bend, said in an interview that this is an important study that includes robust data.

In his opinion, the most significant study finding is the marked increase in epilepsy risk after gestational eclampsia.

“In women who have new-onset epilepsy of unknown cause, asking about having eclampsia or preeclampsia during pregnancy is definitely a worthwhile question,” he said.

Confirming an etiology paints “a better picture” for patients wondering why they’re experiencing seizures, he added.

As with any registry-based study, this one had some acknowledged limitations, “but at the same time, the authors were able to have such a large database that I think this study is very worthwhile,” said Vidic.

The study received support from the Swedish Research Council. Neither Friis nor Vidic had relevant conflicts of interest.

A version of this article appeared on Medscape.com.

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

LOS ANGELES — The median cost of brand-name anti-seizure medications (ASMs) in the United States almost doubled from 2013 to 2023, whereas generic ASM prices declined over the same period, results of a new study showed.

These findings highlight an “urgent need” to examine ASM pricing, said study investigator Pradeep Javarayee, MD, MBA, assistant professor, Department of Neurology, Medical College of Wisconsin, Milwaukee.

“The price disparity between generic and brand-name anti-seizure medications is growing,” said Javarayee. “Understanding these trends is essential for clinicians to make cost-conscious prescribing decisions and to advocate for policies that ensure equitable access to treatment for patients with epilepsy.” 

The findings were presented at American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Concerning Trends

Researchers analyzed prices of ASMs using National Average Drug Acquisition Cost (NADAC) data provided by the Centers for Medicare & Medicaid Services from November 2013 to July 2023.

A publicly available resource, NADAC is widely regarded as the most reliable benchmark for drug reimbursement in the United States, said Javarayee. It is based on the price/unit of Medicaid-covered outpatient drugs collected though monthly surveys of retail community pharmacies across the United States.

The database includes medication names, strengths, formulations, and National Drug Codes.

The study examined 23 US Food and Drug Administration–approved ASMs, encompassing 223 oral formulations, which included 112 brand-name and 111 generic products.

To account for inflation, researchers adjusted ASM prices using the Consumer Price Index for Medicinal Drugs–Seasonally Adjusted. They also explored the effects of the COVID-19 pandemic on drug pricing.

The study uncovered trends that Javarayee found concerning. For example, between 2013 and 2023, the average price of brand-name ASMs increased from $8.71 to $15.43, whereas the average price of generic ASMs decreased from $1.39 to $1.26.

Most generic ASMs remained in the low-cost range ($0-$0.25) during the study period, whereas the proportion of higher-priced brand-name ASMs ($10-$50) increased.

The number of brand-name ASMs with a mean price exceeding $15 rose from two (2013-2016) to six (2017-2019) and then to eight (2020-2023).

 

Unsustainable Price Increases

The study uncovered examples of what Javarayee called “extreme” price differences. For instance, matched brand-name and generic ASMs with price differences of 1000%-9999% increased from 32.88% in 2013-2016 to 41.43% in 2020-2023.

Among brand-name ASMs, cenobamate (Xcopri), which is approved in the United States for partial-onset seizures, had the highest mean price between 2020 and 2023 ($35.59). For generic ASMs, topiramate had the highest mean price in the same time period ($6.64).

Looking at formulation-based cost differences, the study found generic immediate-release formulations were significantly cheaper than extended-release or delayed-release counterparts, with cost differences reaching as high as 7751.20%.

The study also showed the COVID-19 pandemic led to a 24.4% increase in brand-name ASM prices and a 23.1% decrease in generic ASM prices.

The results underscore the need to raise awareness of drug pricing dynamics and call for targeted policy interventions to alleviate the rising cost burden on patients, said Javarayee.

He emphasized that such price increases are unsustainable. “Addressing these disparities is critical not only for improving patient adherence and outcomes but also for reducing the overall economic strain on the healthcare system.”

 

‘Tip of the Iceberg’

Reached for a comment, Tim Welty, a pharmacist in Des Moines, Iowa, who specializes in epilepsy drugs, agreed that the issue of medication costs needs to be addressed.

“I absolutely think physicians and others need to advocate for transparency in pricing,” he said. It’s not unusual for physician requests to have newer ASMs covered for their patients to be denied, he added.

Welty also noted Congress is currently considering bills that address the lack of transparency in the way medications are reimbursed.

This new study doesn’t reveal what patients are paying for their medications, he said. “These data tell me the national average of the cost to the pharmacy, but don’t tell me what the patient is actually paying, or what the insurance companies are actually paying for these medications.”

A “hot topic” in the industry is the role of pharmacy benefit managers, who are contracted by health insurance companies to manage medication portfolios, in influencing drug prices.

Drug pricing is a complicated topic. “There’s a lot more behind this; this is just like a tip of the iceberg,” said Welty.

Also commenting, Jacqueline French, MD, professor, NYU Comprehensive Epilepsy Center, New York City, said the much higher ASM prices are “very problematic,” particularly for drugs that don’t have a generic.

“I wonder how much the drugs for orphan indications, which are usually higher priced, influenced the numbers.”

The good news, though, is that many people “can safely take generics if they’re available,” said French.

The investigators and Welty reported no relevant disclosures.

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

LOS ANGELES — The median cost of brand-name anti-seizure medications (ASMs) in the United States almost doubled from 2013 to 2023, whereas generic ASM prices declined over the same period, results of a new study showed.

These findings highlight an “urgent need” to examine ASM pricing, said study investigator Pradeep Javarayee, MD, MBA, assistant professor, Department of Neurology, Medical College of Wisconsin, Milwaukee.

“The price disparity between generic and brand-name anti-seizure medications is growing,” said Javarayee. “Understanding these trends is essential for clinicians to make cost-conscious prescribing decisions and to advocate for policies that ensure equitable access to treatment for patients with epilepsy.” 

The findings were presented at American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Concerning Trends

Researchers analyzed prices of ASMs using National Average Drug Acquisition Cost (NADAC) data provided by the Centers for Medicare & Medicaid Services from November 2013 to July 2023.

A publicly available resource, NADAC is widely regarded as the most reliable benchmark for drug reimbursement in the United States, said Javarayee. It is based on the price/unit of Medicaid-covered outpatient drugs collected though monthly surveys of retail community pharmacies across the United States.

The database includes medication names, strengths, formulations, and National Drug Codes.

The study examined 23 US Food and Drug Administration–approved ASMs, encompassing 223 oral formulations, which included 112 brand-name and 111 generic products.

To account for inflation, researchers adjusted ASM prices using the Consumer Price Index for Medicinal Drugs–Seasonally Adjusted. They also explored the effects of the COVID-19 pandemic on drug pricing.

The study uncovered trends that Javarayee found concerning. For example, between 2013 and 2023, the average price of brand-name ASMs increased from $8.71 to $15.43, whereas the average price of generic ASMs decreased from $1.39 to $1.26.

Most generic ASMs remained in the low-cost range ($0-$0.25) during the study period, whereas the proportion of higher-priced brand-name ASMs ($10-$50) increased.

The number of brand-name ASMs with a mean price exceeding $15 rose from two (2013-2016) to six (2017-2019) and then to eight (2020-2023).

 

Unsustainable Price Increases

The study uncovered examples of what Javarayee called “extreme” price differences. For instance, matched brand-name and generic ASMs with price differences of 1000%-9999% increased from 32.88% in 2013-2016 to 41.43% in 2020-2023.

Among brand-name ASMs, cenobamate (Xcopri), which is approved in the United States for partial-onset seizures, had the highest mean price between 2020 and 2023 ($35.59). For generic ASMs, topiramate had the highest mean price in the same time period ($6.64).

Looking at formulation-based cost differences, the study found generic immediate-release formulations were significantly cheaper than extended-release or delayed-release counterparts, with cost differences reaching as high as 7751.20%.

The study also showed the COVID-19 pandemic led to a 24.4% increase in brand-name ASM prices and a 23.1% decrease in generic ASM prices.

The results underscore the need to raise awareness of drug pricing dynamics and call for targeted policy interventions to alleviate the rising cost burden on patients, said Javarayee.

He emphasized that such price increases are unsustainable. “Addressing these disparities is critical not only for improving patient adherence and outcomes but also for reducing the overall economic strain on the healthcare system.”

 

‘Tip of the Iceberg’

Reached for a comment, Tim Welty, a pharmacist in Des Moines, Iowa, who specializes in epilepsy drugs, agreed that the issue of medication costs needs to be addressed.

“I absolutely think physicians and others need to advocate for transparency in pricing,” he said. It’s not unusual for physician requests to have newer ASMs covered for their patients to be denied, he added.

Welty also noted Congress is currently considering bills that address the lack of transparency in the way medications are reimbursed.

This new study doesn’t reveal what patients are paying for their medications, he said. “These data tell me the national average of the cost to the pharmacy, but don’t tell me what the patient is actually paying, or what the insurance companies are actually paying for these medications.”

A “hot topic” in the industry is the role of pharmacy benefit managers, who are contracted by health insurance companies to manage medication portfolios, in influencing drug prices.

Drug pricing is a complicated topic. “There’s a lot more behind this; this is just like a tip of the iceberg,” said Welty.

Also commenting, Jacqueline French, MD, professor, NYU Comprehensive Epilepsy Center, New York City, said the much higher ASM prices are “very problematic,” particularly for drugs that don’t have a generic.

“I wonder how much the drugs for orphan indications, which are usually higher priced, influenced the numbers.”

The good news, though, is that many people “can safely take generics if they’re available,” said French.

The investigators and Welty reported no relevant disclosures.

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

LOS ANGELES — The median cost of brand-name anti-seizure medications (ASMs) in the United States almost doubled from 2013 to 2023, whereas generic ASM prices declined over the same period, results of a new study showed.

These findings highlight an “urgent need” to examine ASM pricing, said study investigator Pradeep Javarayee, MD, MBA, assistant professor, Department of Neurology, Medical College of Wisconsin, Milwaukee.

“The price disparity between generic and brand-name anti-seizure medications is growing,” said Javarayee. “Understanding these trends is essential for clinicians to make cost-conscious prescribing decisions and to advocate for policies that ensure equitable access to treatment for patients with epilepsy.” 

The findings were presented at American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Concerning Trends

Researchers analyzed prices of ASMs using National Average Drug Acquisition Cost (NADAC) data provided by the Centers for Medicare & Medicaid Services from November 2013 to July 2023.

A publicly available resource, NADAC is widely regarded as the most reliable benchmark for drug reimbursement in the United States, said Javarayee. It is based on the price/unit of Medicaid-covered outpatient drugs collected though monthly surveys of retail community pharmacies across the United States.

The database includes medication names, strengths, formulations, and National Drug Codes.

The study examined 23 US Food and Drug Administration–approved ASMs, encompassing 223 oral formulations, which included 112 brand-name and 111 generic products.

To account for inflation, researchers adjusted ASM prices using the Consumer Price Index for Medicinal Drugs–Seasonally Adjusted. They also explored the effects of the COVID-19 pandemic on drug pricing.

The study uncovered trends that Javarayee found concerning. For example, between 2013 and 2023, the average price of brand-name ASMs increased from $8.71 to $15.43, whereas the average price of generic ASMs decreased from $1.39 to $1.26.

Most generic ASMs remained in the low-cost range ($0-$0.25) during the study period, whereas the proportion of higher-priced brand-name ASMs ($10-$50) increased.

The number of brand-name ASMs with a mean price exceeding $15 rose from two (2013-2016) to six (2017-2019) and then to eight (2020-2023).

 

Unsustainable Price Increases

The study uncovered examples of what Javarayee called “extreme” price differences. For instance, matched brand-name and generic ASMs with price differences of 1000%-9999% increased from 32.88% in 2013-2016 to 41.43% in 2020-2023.

Among brand-name ASMs, cenobamate (Xcopri), which is approved in the United States for partial-onset seizures, had the highest mean price between 2020 and 2023 ($35.59). For generic ASMs, topiramate had the highest mean price in the same time period ($6.64).

Looking at formulation-based cost differences, the study found generic immediate-release formulations were significantly cheaper than extended-release or delayed-release counterparts, with cost differences reaching as high as 7751.20%.

The study also showed the COVID-19 pandemic led to a 24.4% increase in brand-name ASM prices and a 23.1% decrease in generic ASM prices.

The results underscore the need to raise awareness of drug pricing dynamics and call for targeted policy interventions to alleviate the rising cost burden on patients, said Javarayee.

He emphasized that such price increases are unsustainable. “Addressing these disparities is critical not only for improving patient adherence and outcomes but also for reducing the overall economic strain on the healthcare system.”

 

‘Tip of the Iceberg’

Reached for a comment, Tim Welty, a pharmacist in Des Moines, Iowa, who specializes in epilepsy drugs, agreed that the issue of medication costs needs to be addressed.

“I absolutely think physicians and others need to advocate for transparency in pricing,” he said. It’s not unusual for physician requests to have newer ASMs covered for their patients to be denied, he added.

Welty also noted Congress is currently considering bills that address the lack of transparency in the way medications are reimbursed.

This new study doesn’t reveal what patients are paying for their medications, he said. “These data tell me the national average of the cost to the pharmacy, but don’t tell me what the patient is actually paying, or what the insurance companies are actually paying for these medications.”

A “hot topic” in the industry is the role of pharmacy benefit managers, who are contracted by health insurance companies to manage medication portfolios, in influencing drug prices.

Drug pricing is a complicated topic. “There’s a lot more behind this; this is just like a tip of the iceberg,” said Welty.

Also commenting, Jacqueline French, MD, professor, NYU Comprehensive Epilepsy Center, New York City, said the much higher ASM prices are “very problematic,” particularly for drugs that don’t have a generic.

“I wonder how much the drugs for orphan indications, which are usually higher priced, influenced the numbers.”

The good news, though, is that many people “can safely take generics if they’re available,” said French.

The investigators and Welty reported no relevant disclosures.

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

LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.

In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.

“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.

She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.

The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Unique Survey

Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.

The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.

The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.

Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.

The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.

When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.

The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.

ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.

There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.

For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.

ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.

However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.

Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.

They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.

“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.

 

No Trickle-Down Effect

Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.

“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.

“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.

Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”

She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.

But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”

The investigators and Pack reported no relevant conflicts of interest.

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

LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.

In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.

“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.

She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.

The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Unique Survey

Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.

The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.

The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.

Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.

The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.

When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.

The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.

ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.

There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.

For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.

ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.

However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.

Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.

They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.

“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.

 

No Trickle-Down Effect

Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.

“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.

“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.

Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”

She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.

But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”

The investigators and Pack reported no relevant conflicts of interest.

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

LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.

In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.

“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.

She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.

The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Unique Survey

Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.

The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.

The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.

Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.

The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.

When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.

The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.

ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.

There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.

For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.

ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.

However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.

Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.

They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.

“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.

 

No Trickle-Down Effect

Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.

“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.

“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.

Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”

She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.

But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”

The investigators and Pack reported no relevant conflicts of interest.

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

LOS ANGELES — Only about 27% of patients newly diagnosed with focal epilepsy are seizure-free on initial anti-seizure medications (ASMs), new research suggested.

This is sobering information to pass on to patients with focal epilepsy who may have high expectations based on prior data. “Patients tend to expect things to happen quickly, said study investigator Sarah Barnard, MD, a research fellow at the School of Translational Medicine, Monash University, Melbourne, Australia.

The study was presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

An International Collaboration

The study is part of the International Human Epilepsy Project (HEP), which focuses on new-onset focal epilepsy, one of the most common forms of the disorder. The researchers are aiming to identify factors that influence treatment response in this population.

For example, they will investigate how specific medications and coexisting conditions affect treatment outcomes. Ultimately, the goal is to enable the development of individualized treatment plans for patients, leading to faster and more effective improvements or potential cures for the condition.

“The investigators wanted to focus in on focal epilepsy and exclude patients with more severe phenotypes, such as those with developmental delays or significant brain injury,” said Barnard. Individuals with focal epilepsy are generally healthy, she added.

In addition, previous studies may have used differing definitions of seizure freedom, said Barnard.

The study included 448 patients, median age about 33 years and 60% women, with focal epilepsy who were enrolled at 34 tertiary epilepsy centers in the United States, Europe, and Australia within 4 months of initiating ASM treatment.

Participants were followed for up to 6 years (the median was 3.13 years). The median age at seizure onset was 29 years, and the median age of treatment initiation was 32 years. The most common first-line ASMs were levetiracetam (56.9%) and lamotrigine (16.5%).

Researchers used updated International League Against Epilepsy definitions. Seizure freedom is defined as no seizures for 12 months or three times the longest pretreatment seizure-free interval, whichever is longer.

Results showed that only 27% of patients were seizure-free in the first year after diagnosis even accounting for a 2-month “medication adjustment” period.

 

Managing Expectations

Although the study excluded individuals with more severe types of epilepsy, “we still identified a substantial proportion of treatment-resistant cases, suggesting that much more complex factors are at play,” said Jacqueline French, MD, a study coinvestigator and professor at the NYU Langone’s Comprehensive Epilepsy Center in New York City.

“I don’t think we adequately prepare our patients for the challenges of the first year, which can be quite turbulent,” French said.

However, the seizure freedom rate in this study is lower than previous estimates. “It’s much less than what was predicted in other studies, some of which quote around 50%-55% seizure freedom on the first ASM,” said Barnard.

It’s not clear why there’s such a difference, although it may be related to a predominance in the HEP study of patients taking levetiracetam as the first-line ASM. “We didn’t directly look at the rate of treatment response or seizure freedom on levetiracetam,” which is something that will be addressed in a follow-up study, Barnard added.

The difference could be due to the study including only focal epilepsy patients, “who usually have a different treatment regime,” or it could be related to using updated definitions in this study, she said.

Results also showed that patients are at high risk during the first year of treatment, with two thirds experiencing ongoing or worsening seizures during this period. “People have ongoing seizures for the first year, even if they go on to become seizure-free,” Barnard noted.

Experiencing ongoing seizures has potential implications for driving and for employment, she added.

A self-reported history of a psychological disorder was a risk factor for increased treatment resistance. Upon enrollment, each participant completed the Mini International Neuropsychiatric Interview, which Barnard said is a diagnostic, rather than a screening, tool.

One of the team’s next research steps is to look more closely at the role of depression, anxiety, bipolar disorder, and suicidality on treatment response in this patient population, said Barnard.

 

Important for Patient Counseling

Commenting on the research, Patrick Kwan, MD, PhD, professor, Department of Neuroscience, Monash University, said the research is “very important” in terms of patient counseling.

“For someone newly diagnosed with epilepsy, starting the first medication can be both daunting and confusing, with many uncertainties,” said Kwan. “That’s why it’s valuable to know that nearly a third of patients may not respond to initial treatment.”

He noted that the patients in the study were recruited from major centers, which could attract a specific subset of individuals. “It’s possible that this patient population might represent more severe cases,” he explained.

Kwan also emphasized that the study did not examine the “patterns” of prescription drug choices, adding that he agreed this should be addressed in future analyses.

The researchers and Kwan reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

LOS ANGELES — Only about 27% of patients newly diagnosed with focal epilepsy are seizure-free on initial anti-seizure medications (ASMs), new research suggested.

This is sobering information to pass on to patients with focal epilepsy who may have high expectations based on prior data. “Patients tend to expect things to happen quickly, said study investigator Sarah Barnard, MD, a research fellow at the School of Translational Medicine, Monash University, Melbourne, Australia.

The study was presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

An International Collaboration

The study is part of the International Human Epilepsy Project (HEP), which focuses on new-onset focal epilepsy, one of the most common forms of the disorder. The researchers are aiming to identify factors that influence treatment response in this population.

For example, they will investigate how specific medications and coexisting conditions affect treatment outcomes. Ultimately, the goal is to enable the development of individualized treatment plans for patients, leading to faster and more effective improvements or potential cures for the condition.

“The investigators wanted to focus in on focal epilepsy and exclude patients with more severe phenotypes, such as those with developmental delays or significant brain injury,” said Barnard. Individuals with focal epilepsy are generally healthy, she added.

In addition, previous studies may have used differing definitions of seizure freedom, said Barnard.

The study included 448 patients, median age about 33 years and 60% women, with focal epilepsy who were enrolled at 34 tertiary epilepsy centers in the United States, Europe, and Australia within 4 months of initiating ASM treatment.

Participants were followed for up to 6 years (the median was 3.13 years). The median age at seizure onset was 29 years, and the median age of treatment initiation was 32 years. The most common first-line ASMs were levetiracetam (56.9%) and lamotrigine (16.5%).

Researchers used updated International League Against Epilepsy definitions. Seizure freedom is defined as no seizures for 12 months or three times the longest pretreatment seizure-free interval, whichever is longer.

Results showed that only 27% of patients were seizure-free in the first year after diagnosis even accounting for a 2-month “medication adjustment” period.

 

Managing Expectations

Although the study excluded individuals with more severe types of epilepsy, “we still identified a substantial proportion of treatment-resistant cases, suggesting that much more complex factors are at play,” said Jacqueline French, MD, a study coinvestigator and professor at the NYU Langone’s Comprehensive Epilepsy Center in New York City.

“I don’t think we adequately prepare our patients for the challenges of the first year, which can be quite turbulent,” French said.

However, the seizure freedom rate in this study is lower than previous estimates. “It’s much less than what was predicted in other studies, some of which quote around 50%-55% seizure freedom on the first ASM,” said Barnard.

It’s not clear why there’s such a difference, although it may be related to a predominance in the HEP study of patients taking levetiracetam as the first-line ASM. “We didn’t directly look at the rate of treatment response or seizure freedom on levetiracetam,” which is something that will be addressed in a follow-up study, Barnard added.

The difference could be due to the study including only focal epilepsy patients, “who usually have a different treatment regime,” or it could be related to using updated definitions in this study, she said.

Results also showed that patients are at high risk during the first year of treatment, with two thirds experiencing ongoing or worsening seizures during this period. “People have ongoing seizures for the first year, even if they go on to become seizure-free,” Barnard noted.

Experiencing ongoing seizures has potential implications for driving and for employment, she added.

A self-reported history of a psychological disorder was a risk factor for increased treatment resistance. Upon enrollment, each participant completed the Mini International Neuropsychiatric Interview, which Barnard said is a diagnostic, rather than a screening, tool.

One of the team’s next research steps is to look more closely at the role of depression, anxiety, bipolar disorder, and suicidality on treatment response in this patient population, said Barnard.

 

Important for Patient Counseling

Commenting on the research, Patrick Kwan, MD, PhD, professor, Department of Neuroscience, Monash University, said the research is “very important” in terms of patient counseling.

“For someone newly diagnosed with epilepsy, starting the first medication can be both daunting and confusing, with many uncertainties,” said Kwan. “That’s why it’s valuable to know that nearly a third of patients may not respond to initial treatment.”

He noted that the patients in the study were recruited from major centers, which could attract a specific subset of individuals. “It’s possible that this patient population might represent more severe cases,” he explained.

Kwan also emphasized that the study did not examine the “patterns” of prescription drug choices, adding that he agreed this should be addressed in future analyses.

The researchers and Kwan reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

LOS ANGELES — Only about 27% of patients newly diagnosed with focal epilepsy are seizure-free on initial anti-seizure medications (ASMs), new research suggested.

This is sobering information to pass on to patients with focal epilepsy who may have high expectations based on prior data. “Patients tend to expect things to happen quickly, said study investigator Sarah Barnard, MD, a research fellow at the School of Translational Medicine, Monash University, Melbourne, Australia.

The study was presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

An International Collaboration

The study is part of the International Human Epilepsy Project (HEP), which focuses on new-onset focal epilepsy, one of the most common forms of the disorder. The researchers are aiming to identify factors that influence treatment response in this population.

For example, they will investigate how specific medications and coexisting conditions affect treatment outcomes. Ultimately, the goal is to enable the development of individualized treatment plans for patients, leading to faster and more effective improvements or potential cures for the condition.

“The investigators wanted to focus in on focal epilepsy and exclude patients with more severe phenotypes, such as those with developmental delays or significant brain injury,” said Barnard. Individuals with focal epilepsy are generally healthy, she added.

In addition, previous studies may have used differing definitions of seizure freedom, said Barnard.

The study included 448 patients, median age about 33 years and 60% women, with focal epilepsy who were enrolled at 34 tertiary epilepsy centers in the United States, Europe, and Australia within 4 months of initiating ASM treatment.

Participants were followed for up to 6 years (the median was 3.13 years). The median age at seizure onset was 29 years, and the median age of treatment initiation was 32 years. The most common first-line ASMs were levetiracetam (56.9%) and lamotrigine (16.5%).

Researchers used updated International League Against Epilepsy definitions. Seizure freedom is defined as no seizures for 12 months or three times the longest pretreatment seizure-free interval, whichever is longer.

Results showed that only 27% of patients were seizure-free in the first year after diagnosis even accounting for a 2-month “medication adjustment” period.

 

Managing Expectations

Although the study excluded individuals with more severe types of epilepsy, “we still identified a substantial proportion of treatment-resistant cases, suggesting that much more complex factors are at play,” said Jacqueline French, MD, a study coinvestigator and professor at the NYU Langone’s Comprehensive Epilepsy Center in New York City.

“I don’t think we adequately prepare our patients for the challenges of the first year, which can be quite turbulent,” French said.

However, the seizure freedom rate in this study is lower than previous estimates. “It’s much less than what was predicted in other studies, some of which quote around 50%-55% seizure freedom on the first ASM,” said Barnard.

It’s not clear why there’s such a difference, although it may be related to a predominance in the HEP study of patients taking levetiracetam as the first-line ASM. “We didn’t directly look at the rate of treatment response or seizure freedom on levetiracetam,” which is something that will be addressed in a follow-up study, Barnard added.

The difference could be due to the study including only focal epilepsy patients, “who usually have a different treatment regime,” or it could be related to using updated definitions in this study, she said.

Results also showed that patients are at high risk during the first year of treatment, with two thirds experiencing ongoing or worsening seizures during this period. “People have ongoing seizures for the first year, even if they go on to become seizure-free,” Barnard noted.

Experiencing ongoing seizures has potential implications for driving and for employment, she added.

A self-reported history of a psychological disorder was a risk factor for increased treatment resistance. Upon enrollment, each participant completed the Mini International Neuropsychiatric Interview, which Barnard said is a diagnostic, rather than a screening, tool.

One of the team’s next research steps is to look more closely at the role of depression, anxiety, bipolar disorder, and suicidality on treatment response in this patient population, said Barnard.

 

Important for Patient Counseling

Commenting on the research, Patrick Kwan, MD, PhD, professor, Department of Neuroscience, Monash University, said the research is “very important” in terms of patient counseling.

“For someone newly diagnosed with epilepsy, starting the first medication can be both daunting and confusing, with many uncertainties,” said Kwan. “That’s why it’s valuable to know that nearly a third of patients may not respond to initial treatment.”

He noted that the patients in the study were recruited from major centers, which could attract a specific subset of individuals. “It’s possible that this patient population might represent more severe cases,” he explained.

Kwan also emphasized that the study did not examine the “patterns” of prescription drug choices, adding that he agreed this should be addressed in future analyses.

The researchers and Kwan reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

LOS ANGELES — A mattress designed to detect seizures in individuals with epilepsy who are lying face down and quickly reposition them onto their side could significantly reduce the risk for sudden unexpected death in epilepsy (SUDEP), says one of the experts involved in its development.

When used along with a seizure detection device, Jong Woo Lee, MD, PhD, associate professor of neurology, Harvard Medical School, and Brigham and Women’s Hospital, both in Boston, Massachusetts, estimates the smart mattress could cut SUDEP by more than 50%.

In addition, early results from an observational study are backing this up, he said.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Most SUDEP Cases Found Face Down

SUDEP is the leading cause of death in children with epilepsy and in otherwise healthy adult patients with epilepsy. When his fifth patient died of SUDEP, Lee decided it was time to try to tackle the high mortality rate associated with these unexpected deaths. “I desperately wanted to help, ” he said.

About 70% of SUDEP occurs during sleep, and victims are found face down, or in the prone position, 90% of the time, said Lee.

“Of course, the best way to prevent SUDEP is not to have a seizure, but once you have a seizure and once you’re face down, your risk for death goes up by somewhere between 30 and 100 times,” he explained.

Lee was convinced SUDEP could be prevented by simple interventions that stimulate the patient and turn them over. He noted the incidence of sudden infant death syndrome, “which has similar characteristics” to SUDEP, has been reduced by up to 75% through campaigns that simply advise placing babies on their backs.

“Most of SUDEP happens because your arousal system is knocked out and you just don’t take the breath that you’re supposed to. Just the act of turning people over and vibrating the bed will stimulate them,” he said.

However, it’s crucial that this be done quickly, said Lee. “When you look at patients who died on video and see the EEGs, everybody took their last breath within 3 minutes.”

Because the window of opportunity is so short, “we think that seizure detection devices alone are not going to really be effective because you just can’t get there or react within those 3 minutes.”

There are currently no products that detect the prone position or have the ability to reposition a patient quickly into the recovery sideways position.

Lee and his colleagues developed a smart system that can be embedded in a mattress that detects when someone is having a seizure, determines if that person is face down, and if so, safely stimulates and repositions them.

The mattress is made up of a series of programmable inflatable blocks or “cells” that have pressure, vibration, temperature, and humidity sensors embedded within. “Based on the pressure readings, we can figure out whether the patient is right side up, on their right side, on their left side, or face down,” said Lee.

If the person is face down, he or she can be repositioned within a matter of seconds. “Each of the cells can lift 1000 pounds,” he said. The mattress is “very comfortable,” said Lee, who has tried it out himself.

Eighteen normative control participants have been enrolled for development and training purposes. To date, 10 of these individuals, aged 18-53 years, weighing 100-182 lb, and with a height of 5 ft 2 in to 6 ft 1 in, underwent extensive formal testing on the prototype bed.

Researchers found the mattress responded quickly to different body positions and weights. “We were able to reposition everybody in around 20 seconds,” said Lee.

The overall accuracy of detecting the prone position was 96.8%. There were no cases of a supine or prone position being mistaken for each other.

Researchers are refining the algorithm to improve the accuracy for detecting the prone position and expect to have a completely functional prototype within a few years.

 

Big Step Forward

Commenting on the research, Daniel M. Goldenholz, MD, PhD, assistant professor, Division of Epilepsy, Harvard Beth Israel Deaconess Medical Center, Boston, said the study “is a big step forward in the race to provide an actionable tool to prevent SUDEP.”

The technology “appears to mostly be doing what it’s intended to do, with relatively minor technical errors being made,” he said.

However, it is not clear if this technology can truly save lives, said Goldenholz. “The data we have suggests that lying face down in bed after a seizure is correlated with SUDEP, but that does not mean that if we can simply flip people over, they for sure won’t die.”

Even if the new technology “works perfectly,” it’s still an open question, said Goldenholz. If it does save lives, “this will be a major breakthrough, and one that has been needed for a long time.”

However, even if it does not, he congratulates the team for trying to determine if reducing the prone position can help prevent SUDEP. He would like to see more “high-risk, high-reward” studies in the epilepsy field. “We are in so much need of new innovations.”

He said he was “personally very inspired” by this work. “People are dying from this terrible disease, and this team is building what they hope might save lives.”

The study was funded by the National Institutes of Health. The mattress is being developed by Soterya. Lee reported no equity in Soterya. Goldenholz reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

LOS ANGELES — A mattress designed to detect seizures in individuals with epilepsy who are lying face down and quickly reposition them onto their side could significantly reduce the risk for sudden unexpected death in epilepsy (SUDEP), says one of the experts involved in its development.

When used along with a seizure detection device, Jong Woo Lee, MD, PhD, associate professor of neurology, Harvard Medical School, and Brigham and Women’s Hospital, both in Boston, Massachusetts, estimates the smart mattress could cut SUDEP by more than 50%.

In addition, early results from an observational study are backing this up, he said.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Most SUDEP Cases Found Face Down

SUDEP is the leading cause of death in children with epilepsy and in otherwise healthy adult patients with epilepsy. When his fifth patient died of SUDEP, Lee decided it was time to try to tackle the high mortality rate associated with these unexpected deaths. “I desperately wanted to help, ” he said.

About 70% of SUDEP occurs during sleep, and victims are found face down, or in the prone position, 90% of the time, said Lee.

“Of course, the best way to prevent SUDEP is not to have a seizure, but once you have a seizure and once you’re face down, your risk for death goes up by somewhere between 30 and 100 times,” he explained.

Lee was convinced SUDEP could be prevented by simple interventions that stimulate the patient and turn them over. He noted the incidence of sudden infant death syndrome, “which has similar characteristics” to SUDEP, has been reduced by up to 75% through campaigns that simply advise placing babies on their backs.

“Most of SUDEP happens because your arousal system is knocked out and you just don’t take the breath that you’re supposed to. Just the act of turning people over and vibrating the bed will stimulate them,” he said.

However, it’s crucial that this be done quickly, said Lee. “When you look at patients who died on video and see the EEGs, everybody took their last breath within 3 minutes.”

Because the window of opportunity is so short, “we think that seizure detection devices alone are not going to really be effective because you just can’t get there or react within those 3 minutes.”

There are currently no products that detect the prone position or have the ability to reposition a patient quickly into the recovery sideways position.

Lee and his colleagues developed a smart system that can be embedded in a mattress that detects when someone is having a seizure, determines if that person is face down, and if so, safely stimulates and repositions them.

The mattress is made up of a series of programmable inflatable blocks or “cells” that have pressure, vibration, temperature, and humidity sensors embedded within. “Based on the pressure readings, we can figure out whether the patient is right side up, on their right side, on their left side, or face down,” said Lee.

If the person is face down, he or she can be repositioned within a matter of seconds. “Each of the cells can lift 1000 pounds,” he said. The mattress is “very comfortable,” said Lee, who has tried it out himself.

Eighteen normative control participants have been enrolled for development and training purposes. To date, 10 of these individuals, aged 18-53 years, weighing 100-182 lb, and with a height of 5 ft 2 in to 6 ft 1 in, underwent extensive formal testing on the prototype bed.

Researchers found the mattress responded quickly to different body positions and weights. “We were able to reposition everybody in around 20 seconds,” said Lee.

The overall accuracy of detecting the prone position was 96.8%. There were no cases of a supine or prone position being mistaken for each other.

Researchers are refining the algorithm to improve the accuracy for detecting the prone position and expect to have a completely functional prototype within a few years.

 

Big Step Forward

Commenting on the research, Daniel M. Goldenholz, MD, PhD, assistant professor, Division of Epilepsy, Harvard Beth Israel Deaconess Medical Center, Boston, said the study “is a big step forward in the race to provide an actionable tool to prevent SUDEP.”

The technology “appears to mostly be doing what it’s intended to do, with relatively minor technical errors being made,” he said.

However, it is not clear if this technology can truly save lives, said Goldenholz. “The data we have suggests that lying face down in bed after a seizure is correlated with SUDEP, but that does not mean that if we can simply flip people over, they for sure won’t die.”

Even if the new technology “works perfectly,” it’s still an open question, said Goldenholz. If it does save lives, “this will be a major breakthrough, and one that has been needed for a long time.”

However, even if it does not, he congratulates the team for trying to determine if reducing the prone position can help prevent SUDEP. He would like to see more “high-risk, high-reward” studies in the epilepsy field. “We are in so much need of new innovations.”

He said he was “personally very inspired” by this work. “People are dying from this terrible disease, and this team is building what they hope might save lives.”

The study was funded by the National Institutes of Health. The mattress is being developed by Soterya. Lee reported no equity in Soterya. Goldenholz reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

LOS ANGELES — A mattress designed to detect seizures in individuals with epilepsy who are lying face down and quickly reposition them onto their side could significantly reduce the risk for sudden unexpected death in epilepsy (SUDEP), says one of the experts involved in its development.

When used along with a seizure detection device, Jong Woo Lee, MD, PhD, associate professor of neurology, Harvard Medical School, and Brigham and Women’s Hospital, both in Boston, Massachusetts, estimates the smart mattress could cut SUDEP by more than 50%.

In addition, early results from an observational study are backing this up, he said.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Most SUDEP Cases Found Face Down

SUDEP is the leading cause of death in children with epilepsy and in otherwise healthy adult patients with epilepsy. When his fifth patient died of SUDEP, Lee decided it was time to try to tackle the high mortality rate associated with these unexpected deaths. “I desperately wanted to help, ” he said.

About 70% of SUDEP occurs during sleep, and victims are found face down, or in the prone position, 90% of the time, said Lee.

“Of course, the best way to prevent SUDEP is not to have a seizure, but once you have a seizure and once you’re face down, your risk for death goes up by somewhere between 30 and 100 times,” he explained.

Lee was convinced SUDEP could be prevented by simple interventions that stimulate the patient and turn them over. He noted the incidence of sudden infant death syndrome, “which has similar characteristics” to SUDEP, has been reduced by up to 75% through campaigns that simply advise placing babies on their backs.

“Most of SUDEP happens because your arousal system is knocked out and you just don’t take the breath that you’re supposed to. Just the act of turning people over and vibrating the bed will stimulate them,” he said.

However, it’s crucial that this be done quickly, said Lee. “When you look at patients who died on video and see the EEGs, everybody took their last breath within 3 minutes.”

Because the window of opportunity is so short, “we think that seizure detection devices alone are not going to really be effective because you just can’t get there or react within those 3 minutes.”

There are currently no products that detect the prone position or have the ability to reposition a patient quickly into the recovery sideways position.

Lee and his colleagues developed a smart system that can be embedded in a mattress that detects when someone is having a seizure, determines if that person is face down, and if so, safely stimulates and repositions them.

The mattress is made up of a series of programmable inflatable blocks or “cells” that have pressure, vibration, temperature, and humidity sensors embedded within. “Based on the pressure readings, we can figure out whether the patient is right side up, on their right side, on their left side, or face down,” said Lee.

If the person is face down, he or she can be repositioned within a matter of seconds. “Each of the cells can lift 1000 pounds,” he said. The mattress is “very comfortable,” said Lee, who has tried it out himself.

Eighteen normative control participants have been enrolled for development and training purposes. To date, 10 of these individuals, aged 18-53 years, weighing 100-182 lb, and with a height of 5 ft 2 in to 6 ft 1 in, underwent extensive formal testing on the prototype bed.

Researchers found the mattress responded quickly to different body positions and weights. “We were able to reposition everybody in around 20 seconds,” said Lee.

The overall accuracy of detecting the prone position was 96.8%. There were no cases of a supine or prone position being mistaken for each other.

Researchers are refining the algorithm to improve the accuracy for detecting the prone position and expect to have a completely functional prototype within a few years.

 

Big Step Forward

Commenting on the research, Daniel M. Goldenholz, MD, PhD, assistant professor, Division of Epilepsy, Harvard Beth Israel Deaconess Medical Center, Boston, said the study “is a big step forward in the race to provide an actionable tool to prevent SUDEP.”

The technology “appears to mostly be doing what it’s intended to do, with relatively minor technical errors being made,” he said.

However, it is not clear if this technology can truly save lives, said Goldenholz. “The data we have suggests that lying face down in bed after a seizure is correlated with SUDEP, but that does not mean that if we can simply flip people over, they for sure won’t die.”

Even if the new technology “works perfectly,” it’s still an open question, said Goldenholz. If it does save lives, “this will be a major breakthrough, and one that has been needed for a long time.”

However, even if it does not, he congratulates the team for trying to determine if reducing the prone position can help prevent SUDEP. He would like to see more “high-risk, high-reward” studies in the epilepsy field. “We are in so much need of new innovations.”

He said he was “personally very inspired” by this work. “People are dying from this terrible disease, and this team is building what they hope might save lives.”

The study was funded by the National Institutes of Health. The mattress is being developed by Soterya. Lee reported no equity in Soterya. Goldenholz reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

LOS ANGELES — Individuals with both uncontrolled epilepsy and sleep apnea are at significantly higher risk for mortality than those with epilepsy alone, according to a new analysis of over 2 million patient-years drawn from the Komodo Health Claims Database.

“A 10-year-old with uncontrolled epilepsy and central sleep apnea is about 200 times more likely to die than a general population 10-year-old. That’s comparable to a 10-year-old with {epilepsy and} congestive heart failure. Noncentral sleep apnea is comparable to being paralyzed. It’s a huge risk factor,” said poster presenter Dan Lloyd, advanced analytics lead at UCB, which sponsored the research.

The ordering of sleep apnea tests for patients with epilepsy is widely variable, according to Stefanie Dedeurwaerdere, PhD, who is the innovation and value creation lead at UCB. “Some doctors do that as a general practice, and some don’t. There’s no coherency in the way these studies are requested for epilepsy patients. We want to create some awareness around this topic,” she said, and added that treatment of sleep apnea may improve epileptic seizures.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

The study included mortality rates between January 2018 and December 2022, with a total of 2,355,410 patient-years and 968,993 patients, with an age distribution of 19.1% age 1 to less than 18 years, 23.7% age 18-35 years, and 57.2% age 36 years or older. Sleep apnea prevalences were 0.7% for central sleep apnea (CSA), 14.0% for obstructive sleep apnea (OSA), and 85.3% with no sleep apnea.

Among those aged 1-18 years, the standardized mortality ratio (SMR) for those with uncontrolled epilepsy was 27.7. For those with comorbid OSA, the SMR was 74.2, and for comorbid CSA, the SMR was 135.9. The association was less pronounced in older groups, dipping to 7.0, 11.3, and 19.5 in those aged 18-35 years, and 3.3, 3.1, and 2.8 among those aged 36 years or older.

Among the 1-18 age group, SMRs for other comorbidities included 132.3 for heart failure, 74.9 for hemiplegia/paraplegia, 55.3 for cerebrovascular disease, and 44.6 for chronic pulmonary disease.

Asked for comment, Gordon Buchanan, MD, PhD, welcomed the new work. “The results did not surprise me. I study sleep, epilepsy, and [sudden unexplained death in epilepsy (SUDEP)] in particular ... and every time I speak on these topics, someone asks me about risk of SUDEP in patients with sleep apnea. It’s great to finally have some data,” said Buchanan, a professor of neurology at the University of Iowa, Iowa City.

The authors found that patients undergoing continuous positive airway pressure (CPAP)/bi-level positive airway pressure therapy had a higher mortality risk than those not undergoing CPAP therapy but cautioned that uncontrolled confounders may be contributing to the effect.

Buchanan wondered if treatment with CPAP would be associated with a decreased mortality risk. “I think that would be interesting, but I know that, especially in children, it can be difficult to get them to remain compliant with CPAP. I think that would be interesting to know, if pushing harder to get the kids to comply with CPAP would reduce mortality,” he said.

The specific finding of heightened mortality associated with CSA is interesting, according to Buchanan. “We think of seizures propagating through the brain, maybe through direct synaptic connections or through spreading depolarization. So I think it would make sense that it would hit central regions that would then lead to sleep apnea.” 

The relationship between OSA and epilepsy is likely complex. Epilepsy medications and special diets may influence body composition, which could in turn affect the risk for OSA, as could medications associated with psychiatric comorbidities, according to Buchanan.

The study is retrospective and based on claims data. It does not prove causation, and claims data do not fully capture mortality, which may lead to conservative SMR estimates. The researchers did not control for socioeconomic status, treatment status, and other comorbidities or conditions.

Lloyd and Dedeurwaerdere are employees of UCB, which sponsored the study. Buchanan had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

LOS ANGELES — Individuals with both uncontrolled epilepsy and sleep apnea are at significantly higher risk for mortality than those with epilepsy alone, according to a new analysis of over 2 million patient-years drawn from the Komodo Health Claims Database.

“A 10-year-old with uncontrolled epilepsy and central sleep apnea is about 200 times more likely to die than a general population 10-year-old. That’s comparable to a 10-year-old with {epilepsy and} congestive heart failure. Noncentral sleep apnea is comparable to being paralyzed. It’s a huge risk factor,” said poster presenter Dan Lloyd, advanced analytics lead at UCB, which sponsored the research.

The ordering of sleep apnea tests for patients with epilepsy is widely variable, according to Stefanie Dedeurwaerdere, PhD, who is the innovation and value creation lead at UCB. “Some doctors do that as a general practice, and some don’t. There’s no coherency in the way these studies are requested for epilepsy patients. We want to create some awareness around this topic,” she said, and added that treatment of sleep apnea may improve epileptic seizures.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

The study included mortality rates between January 2018 and December 2022, with a total of 2,355,410 patient-years and 968,993 patients, with an age distribution of 19.1% age 1 to less than 18 years, 23.7% age 18-35 years, and 57.2% age 36 years or older. Sleep apnea prevalences were 0.7% for central sleep apnea (CSA), 14.0% for obstructive sleep apnea (OSA), and 85.3% with no sleep apnea.

Among those aged 1-18 years, the standardized mortality ratio (SMR) for those with uncontrolled epilepsy was 27.7. For those with comorbid OSA, the SMR was 74.2, and for comorbid CSA, the SMR was 135.9. The association was less pronounced in older groups, dipping to 7.0, 11.3, and 19.5 in those aged 18-35 years, and 3.3, 3.1, and 2.8 among those aged 36 years or older.

Among the 1-18 age group, SMRs for other comorbidities included 132.3 for heart failure, 74.9 for hemiplegia/paraplegia, 55.3 for cerebrovascular disease, and 44.6 for chronic pulmonary disease.

Asked for comment, Gordon Buchanan, MD, PhD, welcomed the new work. “The results did not surprise me. I study sleep, epilepsy, and [sudden unexplained death in epilepsy (SUDEP)] in particular ... and every time I speak on these topics, someone asks me about risk of SUDEP in patients with sleep apnea. It’s great to finally have some data,” said Buchanan, a professor of neurology at the University of Iowa, Iowa City.

The authors found that patients undergoing continuous positive airway pressure (CPAP)/bi-level positive airway pressure therapy had a higher mortality risk than those not undergoing CPAP therapy but cautioned that uncontrolled confounders may be contributing to the effect.

Buchanan wondered if treatment with CPAP would be associated with a decreased mortality risk. “I think that would be interesting, but I know that, especially in children, it can be difficult to get them to remain compliant with CPAP. I think that would be interesting to know, if pushing harder to get the kids to comply with CPAP would reduce mortality,” he said.

The specific finding of heightened mortality associated with CSA is interesting, according to Buchanan. “We think of seizures propagating through the brain, maybe through direct synaptic connections or through spreading depolarization. So I think it would make sense that it would hit central regions that would then lead to sleep apnea.” 

The relationship between OSA and epilepsy is likely complex. Epilepsy medications and special diets may influence body composition, which could in turn affect the risk for OSA, as could medications associated with psychiatric comorbidities, according to Buchanan.

The study is retrospective and based on claims data. It does not prove causation, and claims data do not fully capture mortality, which may lead to conservative SMR estimates. The researchers did not control for socioeconomic status, treatment status, and other comorbidities or conditions.

Lloyd and Dedeurwaerdere are employees of UCB, which sponsored the study. Buchanan had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

LOS ANGELES — Individuals with both uncontrolled epilepsy and sleep apnea are at significantly higher risk for mortality than those with epilepsy alone, according to a new analysis of over 2 million patient-years drawn from the Komodo Health Claims Database.

“A 10-year-old with uncontrolled epilepsy and central sleep apnea is about 200 times more likely to die than a general population 10-year-old. That’s comparable to a 10-year-old with {epilepsy and} congestive heart failure. Noncentral sleep apnea is comparable to being paralyzed. It’s a huge risk factor,” said poster presenter Dan Lloyd, advanced analytics lead at UCB, which sponsored the research.

The ordering of sleep apnea tests for patients with epilepsy is widely variable, according to Stefanie Dedeurwaerdere, PhD, who is the innovation and value creation lead at UCB. “Some doctors do that as a general practice, and some don’t. There’s no coherency in the way these studies are requested for epilepsy patients. We want to create some awareness around this topic,” she said, and added that treatment of sleep apnea may improve epileptic seizures.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

The study included mortality rates between January 2018 and December 2022, with a total of 2,355,410 patient-years and 968,993 patients, with an age distribution of 19.1% age 1 to less than 18 years, 23.7% age 18-35 years, and 57.2% age 36 years or older. Sleep apnea prevalences were 0.7% for central sleep apnea (CSA), 14.0% for obstructive sleep apnea (OSA), and 85.3% with no sleep apnea.

Among those aged 1-18 years, the standardized mortality ratio (SMR) for those with uncontrolled epilepsy was 27.7. For those with comorbid OSA, the SMR was 74.2, and for comorbid CSA, the SMR was 135.9. The association was less pronounced in older groups, dipping to 7.0, 11.3, and 19.5 in those aged 18-35 years, and 3.3, 3.1, and 2.8 among those aged 36 years or older.

Among the 1-18 age group, SMRs for other comorbidities included 132.3 for heart failure, 74.9 for hemiplegia/paraplegia, 55.3 for cerebrovascular disease, and 44.6 for chronic pulmonary disease.

Asked for comment, Gordon Buchanan, MD, PhD, welcomed the new work. “The results did not surprise me. I study sleep, epilepsy, and [sudden unexplained death in epilepsy (SUDEP)] in particular ... and every time I speak on these topics, someone asks me about risk of SUDEP in patients with sleep apnea. It’s great to finally have some data,” said Buchanan, a professor of neurology at the University of Iowa, Iowa City.

The authors found that patients undergoing continuous positive airway pressure (CPAP)/bi-level positive airway pressure therapy had a higher mortality risk than those not undergoing CPAP therapy but cautioned that uncontrolled confounders may be contributing to the effect.

Buchanan wondered if treatment with CPAP would be associated with a decreased mortality risk. “I think that would be interesting, but I know that, especially in children, it can be difficult to get them to remain compliant with CPAP. I think that would be interesting to know, if pushing harder to get the kids to comply with CPAP would reduce mortality,” he said.

The specific finding of heightened mortality associated with CSA is interesting, according to Buchanan. “We think of seizures propagating through the brain, maybe through direct synaptic connections or through spreading depolarization. So I think it would make sense that it would hit central regions that would then lead to sleep apnea.” 

The relationship between OSA and epilepsy is likely complex. Epilepsy medications and special diets may influence body composition, which could in turn affect the risk for OSA, as could medications associated with psychiatric comorbidities, according to Buchanan.

The study is retrospective and based on claims data. It does not prove causation, and claims data do not fully capture mortality, which may lead to conservative SMR estimates. The researchers did not control for socioeconomic status, treatment status, and other comorbidities or conditions.

Lloyd and Dedeurwaerdere are employees of UCB, which sponsored the study. Buchanan had no relevant financial disclosures.

A version of this article appeared on Medscape.com.