Epilepsy Resource Center

BOSTON – Noninvasive tests performed in midlife may help identify people who are at risk of late-onset epilepsy, a new study suggests. New data from the Framingham Heart Study show those who scored better on a neurocognitive test that measures executive function were 75% less likely to develop late-onset epilepsy.

An analysis of MRI revealed that those with higher cortical volumes also had a lower risk of epilepsy later in life, while those with higher white matter hyperintensities had an increased risk.

The study could help identify at-risk individuals years before symptoms of epilepsy appear.

“We present possible markers that could potentially identify patients at risk for developing late-onset epilepsy, even in the preclinical phase and before the clinical manifestation of conditions like stroke and dementia that are known now to be linked with the condition,” said lead investigator Maria Stefanidou, MD, assistant professor of neurology at Boston University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Protection against late-onset epilepsy?

Hypertension and stroke are known risk factors for late-onset epilepsy. Dementia is also a known risk factor. But in about 30% of cases, the cause of epilepsy in older individuals is unknown.

For this study, investigators analyzed data from the offspring cohort of the Framingham Heart Study. Participants were at least 45 years old; underwent neuropsychological evaluation and brain MRI; and had no prior history of stroke, dementia, or epilepsy. Cognitive measures included Visual Reproductions Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making B-A (TrB-TrA), and the Hooper Visual Organization Test.

Participants also underwent an MRI to measure total cerebral brain volume, cortical gray matter volume, white matter hyperintensities, and hippocampal volume.

After a mean follow-up of 13.5 years, late-onset epilepsy was diagnosed in 31 of participants who underwent neuropsychological testing (n = 2,349) and in 27 of those who underwent MRI (n = 2,056).

Better performance on the TrB-TrA test (a measure of executive function, processing speed, and occult vascular injury) was associated with a reduced risk of late-onset epilepsy (adjusted hazard ratio, 0.25; P = .011).

The findings held even after adjusting for age, sex, educational level, and known risk factors for late-onset epilepsy, such as hypertension (aHR, 0.30; P = .0401).

Higher white matter hyperintensities, a measure of occult vascular injury, was associated with increased epilepsy risk (aHR, 1.5; P = .042) when adjusted only for age, sex, and education, but was no longer significant after adjusting for hypertension and other risk factors (aHR, 1.47; P = .065).

The analysis also revealed that participants with a higher cortical gray matter volume had a lower risk for late-onset epilepsy (aHR, 0.73; P = .001).

“There is increasing literature supporting that late-onset epilepsy may be secondary to accumulative occult cerebrovascular and neurodegenerative processes that occur during aging,” Dr. Stefanidou said. “Our findings likely reflect that a lesser degree of occult vascular brain injury in midlife may be protective against late-onset epilepsy.”

However, the epidemiological study points to association, not causation, Dr. Stefanidou cautions.

“Further studies will be needed to study our observations in the clinical setting,” she said.
 

‘Intriguing’ findings

Commenting on the findings, Joseph Sirven, MD, a neurologist at the Mayo Clinic in Jacksonville, Fla., said the findings are “intriguing,” but also raise some questions. “Late-onset epilepsy remains an issue for many and it’s common,” said Dr. Sirven, who has patients with late-onset epilepsy.

Dr. Sirven was particularly interested in the findings on white matter hyperintensities. “Hippocampal volumes have been used but not so much cortical volumes,” he said. “I would like to know more about how white matter changes suggest pathology that would explain epilepsy.”

Study funding was not disclosed. Dr. Stefanidou and Dr. Sirven report no relevant financial relationships.

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

BOSTON – Noninvasive tests performed in midlife may help identify people who are at risk of late-onset epilepsy, a new study suggests. New data from the Framingham Heart Study show those who scored better on a neurocognitive test that measures executive function were 75% less likely to develop late-onset epilepsy.

An analysis of MRI revealed that those with higher cortical volumes also had a lower risk of epilepsy later in life, while those with higher white matter hyperintensities had an increased risk.

The study could help identify at-risk individuals years before symptoms of epilepsy appear.

“We present possible markers that could potentially identify patients at risk for developing late-onset epilepsy, even in the preclinical phase and before the clinical manifestation of conditions like stroke and dementia that are known now to be linked with the condition,” said lead investigator Maria Stefanidou, MD, assistant professor of neurology at Boston University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Protection against late-onset epilepsy?

Hypertension and stroke are known risk factors for late-onset epilepsy. Dementia is also a known risk factor. But in about 30% of cases, the cause of epilepsy in older individuals is unknown.

For this study, investigators analyzed data from the offspring cohort of the Framingham Heart Study. Participants were at least 45 years old; underwent neuropsychological evaluation and brain MRI; and had no prior history of stroke, dementia, or epilepsy. Cognitive measures included Visual Reproductions Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making B-A (TrB-TrA), and the Hooper Visual Organization Test.

Participants also underwent an MRI to measure total cerebral brain volume, cortical gray matter volume, white matter hyperintensities, and hippocampal volume.

After a mean follow-up of 13.5 years, late-onset epilepsy was diagnosed in 31 of participants who underwent neuropsychological testing (n = 2,349) and in 27 of those who underwent MRI (n = 2,056).

Better performance on the TrB-TrA test (a measure of executive function, processing speed, and occult vascular injury) was associated with a reduced risk of late-onset epilepsy (adjusted hazard ratio, 0.25; P = .011).

The findings held even after adjusting for age, sex, educational level, and known risk factors for late-onset epilepsy, such as hypertension (aHR, 0.30; P = .0401).

Higher white matter hyperintensities, a measure of occult vascular injury, was associated with increased epilepsy risk (aHR, 1.5; P = .042) when adjusted only for age, sex, and education, but was no longer significant after adjusting for hypertension and other risk factors (aHR, 1.47; P = .065).

The analysis also revealed that participants with a higher cortical gray matter volume had a lower risk for late-onset epilepsy (aHR, 0.73; P = .001).

“There is increasing literature supporting that late-onset epilepsy may be secondary to accumulative occult cerebrovascular and neurodegenerative processes that occur during aging,” Dr. Stefanidou said. “Our findings likely reflect that a lesser degree of occult vascular brain injury in midlife may be protective against late-onset epilepsy.”

However, the epidemiological study points to association, not causation, Dr. Stefanidou cautions.

“Further studies will be needed to study our observations in the clinical setting,” she said.
 

‘Intriguing’ findings

Commenting on the findings, Joseph Sirven, MD, a neurologist at the Mayo Clinic in Jacksonville, Fla., said the findings are “intriguing,” but also raise some questions. “Late-onset epilepsy remains an issue for many and it’s common,” said Dr. Sirven, who has patients with late-onset epilepsy.

Dr. Sirven was particularly interested in the findings on white matter hyperintensities. “Hippocampal volumes have been used but not so much cortical volumes,” he said. “I would like to know more about how white matter changes suggest pathology that would explain epilepsy.”

Study funding was not disclosed. Dr. Stefanidou and Dr. Sirven report no relevant financial relationships.

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

BOSTON – Noninvasive tests performed in midlife may help identify people who are at risk of late-onset epilepsy, a new study suggests. New data from the Framingham Heart Study show those who scored better on a neurocognitive test that measures executive function were 75% less likely to develop late-onset epilepsy.

An analysis of MRI revealed that those with higher cortical volumes also had a lower risk of epilepsy later in life, while those with higher white matter hyperintensities had an increased risk.

The study could help identify at-risk individuals years before symptoms of epilepsy appear.

“We present possible markers that could potentially identify patients at risk for developing late-onset epilepsy, even in the preclinical phase and before the clinical manifestation of conditions like stroke and dementia that are known now to be linked with the condition,” said lead investigator Maria Stefanidou, MD, assistant professor of neurology at Boston University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Protection against late-onset epilepsy?

Hypertension and stroke are known risk factors for late-onset epilepsy. Dementia is also a known risk factor. But in about 30% of cases, the cause of epilepsy in older individuals is unknown.

For this study, investigators analyzed data from the offspring cohort of the Framingham Heart Study. Participants were at least 45 years old; underwent neuropsychological evaluation and brain MRI; and had no prior history of stroke, dementia, or epilepsy. Cognitive measures included Visual Reproductions Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making B-A (TrB-TrA), and the Hooper Visual Organization Test.

Participants also underwent an MRI to measure total cerebral brain volume, cortical gray matter volume, white matter hyperintensities, and hippocampal volume.

After a mean follow-up of 13.5 years, late-onset epilepsy was diagnosed in 31 of participants who underwent neuropsychological testing (n = 2,349) and in 27 of those who underwent MRI (n = 2,056).

Better performance on the TrB-TrA test (a measure of executive function, processing speed, and occult vascular injury) was associated with a reduced risk of late-onset epilepsy (adjusted hazard ratio, 0.25; P = .011).

The findings held even after adjusting for age, sex, educational level, and known risk factors for late-onset epilepsy, such as hypertension (aHR, 0.30; P = .0401).

Higher white matter hyperintensities, a measure of occult vascular injury, was associated with increased epilepsy risk (aHR, 1.5; P = .042) when adjusted only for age, sex, and education, but was no longer significant after adjusting for hypertension and other risk factors (aHR, 1.47; P = .065).

The analysis also revealed that participants with a higher cortical gray matter volume had a lower risk for late-onset epilepsy (aHR, 0.73; P = .001).

“There is increasing literature supporting that late-onset epilepsy may be secondary to accumulative occult cerebrovascular and neurodegenerative processes that occur during aging,” Dr. Stefanidou said. “Our findings likely reflect that a lesser degree of occult vascular brain injury in midlife may be protective against late-onset epilepsy.”

However, the epidemiological study points to association, not causation, Dr. Stefanidou cautions.

“Further studies will be needed to study our observations in the clinical setting,” she said.
 

‘Intriguing’ findings

Commenting on the findings, Joseph Sirven, MD, a neurologist at the Mayo Clinic in Jacksonville, Fla., said the findings are “intriguing,” but also raise some questions. “Late-onset epilepsy remains an issue for many and it’s common,” said Dr. Sirven, who has patients with late-onset epilepsy.

Dr. Sirven was particularly interested in the findings on white matter hyperintensities. “Hippocampal volumes have been used but not so much cortical volumes,” he said. “I would like to know more about how white matter changes suggest pathology that would explain epilepsy.”

Study funding was not disclosed. Dr. Stefanidou and Dr. Sirven report no relevant financial relationships.

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

BOSTON – An experimental neural cell therapy is safe and led to greater than 90% reduction in seizures in two patients with drug-resistant mesial temporal lobe epilepsy (MTLE) in the first-in-human test of the novel therapy.

“It is notable that the early significant seizure reduction observed in this study appears to be durable in these first two patients treated with a single administration of NRTX-1001,” principal investigator Robert Beach, MD, PhD, said in a news release.

“It is also encouraging that the first patient has been free from disabling seizures from the second month on and has shown improved memory performance on multiple cognitive tests, as memory problems can be an issue for individuals with drug-resistant MTLE,” said Dr. Beach, chief of epilepsy and professor of neurology at State University of New York, Syracuse.

The findings were presented at the annual meeting of the American Academy of Neurology.
 

Restorative not destructive

NRTX-1001 therapy (Neurona Therapeutics) is a one-time dose of an injectable suspension of high-purity inhibitory interneurons that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The interneurons are intended to integrate and innervate on-target, providing long-term GABAergic inhibition to repair hyperexcitable neural networks.

Preclinical work in animal models of epilepsy has provided strong support for both the safety and the efficacy of boosting inhibition in the seizure focus using implanted human inhibitory interneurons.

This therapy is “potentially restorative instead of just destructive, like epilepsy surgery,” study investigator David Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center, Oregon Health & Science University in Portland, said during a press briefing.

In the first two patients, the cells were implanted in the seizure focus using MRI guidance through a tiny opening in the back of the skull. The patients recovered overnight and went home the next day.

The first patient had a 9-year history of drug-resistant epilepsy and was averaging 30 seizures per month at baseline. Testing confirmed that the seizures were coming from a single focus on the right temporal lobe. The implant was uncomplicated, and the cells were delivered to the seizure focus on target.

To date, there have been no serious or unexpected adverse events from the implant. At 9 months of follow-up the patient has had a 93% reduction in seizures overall and is free of all seizures causing impairment of awareness, “which was the most debilitating seizure type for this patient,” Dr. Spencer noted.

Studies of brain metabolism in the area of the implant have shown favorable markers of increased inhibition and decreased inflammation. Cognitive testing at 6 months showed no worsening of memory function or cognition. And, in fact, there were some mild improvements, he said.

The second patient had an 8-year history of drug-resistant epilepsy, averaging 14 focal seizures per month at baseline. Testing also confirmed seizure onset in a single focus in the right temporal lobe and the cells were again implanted without complication on target. Five months after treatment, the patient has had a 94% reduction in seizures and no serious adverse events.
 

‘Hot off the press’

Epilepsy affects about 3.5 million people in the United States. About two-thirds of people with epilepsy get good control of their seizures using antiseizure medication.

For seizures that are uncontrolled with medication, identifying the seizure focus and removing it surgically can often result in seizure freedom in a high proportion of patients. But not all patients are candidates for epilepsy surgery, and for those who can have it the surgery itself carries some risks, including diminished cognition and memory.

“While these are still early days, we’re encouraged by the positive safety findings so far, and the early seizure responses” with neural cell therapy, Dr. Spencer told reporters.

Given the positive results in the first two patients, additional patients will be treated “with careful safety review all along the way. This is going to be rolling out over the next several years,” Dr. Spencer said. Patient recruitment is underway at epilepsy centers across the United States.

Briefing moderator Natalia Rost, MD, MPH, chair of the AAN science committee, said, “This is a true example of emerging science. It’s literally hot off the press,” and the preliminary results are “very promising.”

Dr. Rost, chief of the stroke division at Massachusetts General Hospital in Boston, noted that this type of cell therapy implant is “very novel and representative of where the field is moving, when no traditional solutions exist for common neurological problems.” 

The study was sponsored by Neurona Therapeutics and funded in part by the California Institute for Regenerative Medicine. Dr. Beach and Dr. Spencer report no relevant financial relationships. Several investigators are employees of Neurona Therapeutics. Dr. Rost reports no relevant financial relationships.

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

BOSTON – An experimental neural cell therapy is safe and led to greater than 90% reduction in seizures in two patients with drug-resistant mesial temporal lobe epilepsy (MTLE) in the first-in-human test of the novel therapy.

“It is notable that the early significant seizure reduction observed in this study appears to be durable in these first two patients treated with a single administration of NRTX-1001,” principal investigator Robert Beach, MD, PhD, said in a news release.

“It is also encouraging that the first patient has been free from disabling seizures from the second month on and has shown improved memory performance on multiple cognitive tests, as memory problems can be an issue for individuals with drug-resistant MTLE,” said Dr. Beach, chief of epilepsy and professor of neurology at State University of New York, Syracuse.

The findings were presented at the annual meeting of the American Academy of Neurology.
 

Restorative not destructive

NRTX-1001 therapy (Neurona Therapeutics) is a one-time dose of an injectable suspension of high-purity inhibitory interneurons that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The interneurons are intended to integrate and innervate on-target, providing long-term GABAergic inhibition to repair hyperexcitable neural networks.

Preclinical work in animal models of epilepsy has provided strong support for both the safety and the efficacy of boosting inhibition in the seizure focus using implanted human inhibitory interneurons.

This therapy is “potentially restorative instead of just destructive, like epilepsy surgery,” study investigator David Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center, Oregon Health & Science University in Portland, said during a press briefing.

In the first two patients, the cells were implanted in the seizure focus using MRI guidance through a tiny opening in the back of the skull. The patients recovered overnight and went home the next day.

The first patient had a 9-year history of drug-resistant epilepsy and was averaging 30 seizures per month at baseline. Testing confirmed that the seizures were coming from a single focus on the right temporal lobe. The implant was uncomplicated, and the cells were delivered to the seizure focus on target.

To date, there have been no serious or unexpected adverse events from the implant. At 9 months of follow-up the patient has had a 93% reduction in seizures overall and is free of all seizures causing impairment of awareness, “which was the most debilitating seizure type for this patient,” Dr. Spencer noted.

Studies of brain metabolism in the area of the implant have shown favorable markers of increased inhibition and decreased inflammation. Cognitive testing at 6 months showed no worsening of memory function or cognition. And, in fact, there were some mild improvements, he said.

The second patient had an 8-year history of drug-resistant epilepsy, averaging 14 focal seizures per month at baseline. Testing also confirmed seizure onset in a single focus in the right temporal lobe and the cells were again implanted without complication on target. Five months after treatment, the patient has had a 94% reduction in seizures and no serious adverse events.
 

‘Hot off the press’

Epilepsy affects about 3.5 million people in the United States. About two-thirds of people with epilepsy get good control of their seizures using antiseizure medication.

For seizures that are uncontrolled with medication, identifying the seizure focus and removing it surgically can often result in seizure freedom in a high proportion of patients. But not all patients are candidates for epilepsy surgery, and for those who can have it the surgery itself carries some risks, including diminished cognition and memory.

“While these are still early days, we’re encouraged by the positive safety findings so far, and the early seizure responses” with neural cell therapy, Dr. Spencer told reporters.

Given the positive results in the first two patients, additional patients will be treated “with careful safety review all along the way. This is going to be rolling out over the next several years,” Dr. Spencer said. Patient recruitment is underway at epilepsy centers across the United States.

Briefing moderator Natalia Rost, MD, MPH, chair of the AAN science committee, said, “This is a true example of emerging science. It’s literally hot off the press,” and the preliminary results are “very promising.”

Dr. Rost, chief of the stroke division at Massachusetts General Hospital in Boston, noted that this type of cell therapy implant is “very novel and representative of where the field is moving, when no traditional solutions exist for common neurological problems.” 

The study was sponsored by Neurona Therapeutics and funded in part by the California Institute for Regenerative Medicine. Dr. Beach and Dr. Spencer report no relevant financial relationships. Several investigators are employees of Neurona Therapeutics. Dr. Rost reports no relevant financial relationships.

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

BOSTON – An experimental neural cell therapy is safe and led to greater than 90% reduction in seizures in two patients with drug-resistant mesial temporal lobe epilepsy (MTLE) in the first-in-human test of the novel therapy.

“It is notable that the early significant seizure reduction observed in this study appears to be durable in these first two patients treated with a single administration of NRTX-1001,” principal investigator Robert Beach, MD, PhD, said in a news release.

“It is also encouraging that the first patient has been free from disabling seizures from the second month on and has shown improved memory performance on multiple cognitive tests, as memory problems can be an issue for individuals with drug-resistant MTLE,” said Dr. Beach, chief of epilepsy and professor of neurology at State University of New York, Syracuse.

The findings were presented at the annual meeting of the American Academy of Neurology.
 

Restorative not destructive

NRTX-1001 therapy (Neurona Therapeutics) is a one-time dose of an injectable suspension of high-purity inhibitory interneurons that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The interneurons are intended to integrate and innervate on-target, providing long-term GABAergic inhibition to repair hyperexcitable neural networks.

Preclinical work in animal models of epilepsy has provided strong support for both the safety and the efficacy of boosting inhibition in the seizure focus using implanted human inhibitory interneurons.

This therapy is “potentially restorative instead of just destructive, like epilepsy surgery,” study investigator David Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center, Oregon Health & Science University in Portland, said during a press briefing.

In the first two patients, the cells were implanted in the seizure focus using MRI guidance through a tiny opening in the back of the skull. The patients recovered overnight and went home the next day.

The first patient had a 9-year history of drug-resistant epilepsy and was averaging 30 seizures per month at baseline. Testing confirmed that the seizures were coming from a single focus on the right temporal lobe. The implant was uncomplicated, and the cells were delivered to the seizure focus on target.

To date, there have been no serious or unexpected adverse events from the implant. At 9 months of follow-up the patient has had a 93% reduction in seizures overall and is free of all seizures causing impairment of awareness, “which was the most debilitating seizure type for this patient,” Dr. Spencer noted.

Studies of brain metabolism in the area of the implant have shown favorable markers of increased inhibition and decreased inflammation. Cognitive testing at 6 months showed no worsening of memory function or cognition. And, in fact, there were some mild improvements, he said.

The second patient had an 8-year history of drug-resistant epilepsy, averaging 14 focal seizures per month at baseline. Testing also confirmed seizure onset in a single focus in the right temporal lobe and the cells were again implanted without complication on target. Five months after treatment, the patient has had a 94% reduction in seizures and no serious adverse events.
 

‘Hot off the press’

Epilepsy affects about 3.5 million people in the United States. About two-thirds of people with epilepsy get good control of their seizures using antiseizure medication.

For seizures that are uncontrolled with medication, identifying the seizure focus and removing it surgically can often result in seizure freedom in a high proportion of patients. But not all patients are candidates for epilepsy surgery, and for those who can have it the surgery itself carries some risks, including diminished cognition and memory.

“While these are still early days, we’re encouraged by the positive safety findings so far, and the early seizure responses” with neural cell therapy, Dr. Spencer told reporters.

Given the positive results in the first two patients, additional patients will be treated “with careful safety review all along the way. This is going to be rolling out over the next several years,” Dr. Spencer said. Patient recruitment is underway at epilepsy centers across the United States.

Briefing moderator Natalia Rost, MD, MPH, chair of the AAN science committee, said, “This is a true example of emerging science. It’s literally hot off the press,” and the preliminary results are “very promising.”

Dr. Rost, chief of the stroke division at Massachusetts General Hospital in Boston, noted that this type of cell therapy implant is “very novel and representative of where the field is moving, when no traditional solutions exist for common neurological problems.” 

The study was sponsored by Neurona Therapeutics and funded in part by the California Institute for Regenerative Medicine. Dr. Beach and Dr. Spencer report no relevant financial relationships. Several investigators are employees of Neurona Therapeutics. Dr. Rost reports no relevant financial relationships.

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

Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, despite an explosion of third-generation drugs, an abundance of new surgical approaches, and a whole new category of treatment in the form of neurostimulation devices, response rates in epilepsy have not budged, with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.

But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
 

Simpler times

In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.

“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.

Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”

Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”

For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
 

More drug options

Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”

Disease-modifying therapies

Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”

Improving patients’ lives

While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.

Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”

Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, despite an explosion of third-generation drugs, an abundance of new surgical approaches, and a whole new category of treatment in the form of neurostimulation devices, response rates in epilepsy have not budged, with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.

But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
 

Simpler times

In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.

“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.

Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”

Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”

For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
 

More drug options

Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”

Disease-modifying therapies

Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”

Improving patients’ lives

While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.

Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”

Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, despite an explosion of third-generation drugs, an abundance of new surgical approaches, and a whole new category of treatment in the form of neurostimulation devices, response rates in epilepsy have not budged, with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.

But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
 

Simpler times

In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.

“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.

Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”

Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”

For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
 

More drug options

Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”

Disease-modifying therapies

Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”

Improving patients’ lives

While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.

Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”

People of color with epilepsy, including Black, Hispanic, and Native Hawaiian and other Pacific Islander patients, are significantly less likely to be prescribed the latest antiseizure medications (ASMs), compared with their White counterparts, new research shows.

Even after controlling for epilepsy severity, comorbid conditions, and other factors that might affect medication choice, researchers found that newer medication use was 29% less likely in Black patients, 23% less likely in Native Hawaiian and other Pacific Islander patients, and 7% less likely in Hispanic patients, compared with White individuals.

“I hope that clinicians will see from our findings that minoritized patients with epilepsy face a myriad of barriers in receiving the highest quality of care, including ASM use,” said lead investigator Wyatt P. Bensken, PhD, adjunct assistant professor of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland. “Considering your patients’ barriers, and how that influences their care – including ASM selection – will be critical to helping reduce these population-level inequities.”

A prompt for practice change

For the study, researchers used Medicaid claims for more than 78,000 people who had filled at least two prescriptions for an ASM between 2010 and 2014.

Most patients were White (53.4%); 22.6% were Black; 11.9% were Hispanic; 1.6% were Asian; 1.5% were Native Hawaiian or other Pacific Islander; 0.6% American Indian or Alaskan Native; and 8.3% were classified as “other.”

One-quarter of participants were taking an older ASM, such as carbamazepine, phenytoin, and valproate. About 65% were taking second-generation ASMs, including gabapentin, levetiracetam, and zonisamide. A little less than 10% were taking lacosamide, perampenel, or another third-generation ASM.

Compared with White patients, newer medication prescriptions were significantly less likely in Black individuals (adjusted odds ratio, 0.71; 95% confidence interval, 0.68-0.75), Native Hawaiian or other Pacific Islanders (aOR, 0.77; 95% CI, 0.67-0.88), and Hispanic patients (aOR, 0.93; 95% CI, 0.88-0.99).

Third-generation ASMs were used by 10.7% of White patients versus 6% of Black individuals and 5.1% of American Indian or Alaskan Native patients.

Researchers also found that taking a second-generation ASM was associated with better treatment adherence (aOR, 1.17; 95% CI, 1.11-1.23) and that patients on newer ASMs were more than three times as likely to be under the care of a neurologist (aOR, 3.26; 95% CI, 3.13-3.41).

The findings draw attention to racial inequities surrounding access to medication and specialists and subspecialists, Dr. Bensken said. Identifying specific barriers and developing solutions is the long-range goal, he added.

“In the interim, increasing the attention to these inequities will, we hope, prompt changes across practices,” Dr. Bensken said.
 

A ‘wake-up call’

Commenting on the findings, Joseph Sirven, MD, professor of neurology at the Mayo Clinic Florida, Jacksonville, said the results were “striking” because newer ASMs are generally the go-to for most physicians who treat epilepsy. 

“Use of first-generation ASMs is typically reserved [for] if one runs out of options,” Dr. Sirven said.

This study and others like it should serve as a “wake-up call” for clinicians, Dr. Sirven added.

“This study is important because it shows that whether we realize it or not, race and ethnicities are playing a role in ASM, and this is related to financial access to newer-generation drugs,” he said. “Similar findings are seen in impoverished countries where first-generation ASM drugs are routinely used because of drug pricing.”
 

More to explore

Also commenting on the study, Scott Mintzer, MD, a professor and director of the Epilepsy Monitoring Unit at Thomas Jefferson University, Philadelphia, said using first-generation ASMs as a proxy for quality of care is “a very innovative concept.”

“From that perspective, the finding that racial minority patients are more likely to be on a first-generation drug is not surprising. But after that it gets far more complicated to interpret,” he added.  

Neither adherence nor care by a neurologist was different in a consistent direction within the various minority populations, Dr. Mintzer noted. In addition, Black patients were as likely to see a neurologist as White patients but still more likely to be on a first-generation drug.

There are also a few caveats to the findings that should be considered, Dr. Mintzer added. First, the sample included only Medicaid recipients, nearly 35% of whom had a comorbid psychosis. Those and other characteristics of the study pool suggest participants aren’t representative of the United States population as a whole. Second, significant shifts in ASM use have occurred since the study data cutoff in 2014, none of which are reflected in these findings.

“So, I don’t think we can really say how to address this yet,” Dr. Mintzer said. “There’s a lot to explore about whether this is still occurring, how generalizable these findings are, and what they might be due to, as there are a host of potential explanations, which the authors themselves acknowledge.”

The study was funded by the U.S. Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities. Dr. Bensken has received support for this work from NIMHD and serves on the Editorial Board of the journal Neurology. Dr. Sirven and Mintzer report no relevant financial relationships.

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

People of color with epilepsy, including Black, Hispanic, and Native Hawaiian and other Pacific Islander patients, are significantly less likely to be prescribed the latest antiseizure medications (ASMs), compared with their White counterparts, new research shows.

Even after controlling for epilepsy severity, comorbid conditions, and other factors that might affect medication choice, researchers found that newer medication use was 29% less likely in Black patients, 23% less likely in Native Hawaiian and other Pacific Islander patients, and 7% less likely in Hispanic patients, compared with White individuals.

“I hope that clinicians will see from our findings that minoritized patients with epilepsy face a myriad of barriers in receiving the highest quality of care, including ASM use,” said lead investigator Wyatt P. Bensken, PhD, adjunct assistant professor of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland. “Considering your patients’ barriers, and how that influences their care – including ASM selection – will be critical to helping reduce these population-level inequities.”

A prompt for practice change

For the study, researchers used Medicaid claims for more than 78,000 people who had filled at least two prescriptions for an ASM between 2010 and 2014.

Most patients were White (53.4%); 22.6% were Black; 11.9% were Hispanic; 1.6% were Asian; 1.5% were Native Hawaiian or other Pacific Islander; 0.6% American Indian or Alaskan Native; and 8.3% were classified as “other.”

One-quarter of participants were taking an older ASM, such as carbamazepine, phenytoin, and valproate. About 65% were taking second-generation ASMs, including gabapentin, levetiracetam, and zonisamide. A little less than 10% were taking lacosamide, perampenel, or another third-generation ASM.

Compared with White patients, newer medication prescriptions were significantly less likely in Black individuals (adjusted odds ratio, 0.71; 95% confidence interval, 0.68-0.75), Native Hawaiian or other Pacific Islanders (aOR, 0.77; 95% CI, 0.67-0.88), and Hispanic patients (aOR, 0.93; 95% CI, 0.88-0.99).

Third-generation ASMs were used by 10.7% of White patients versus 6% of Black individuals and 5.1% of American Indian or Alaskan Native patients.

Researchers also found that taking a second-generation ASM was associated with better treatment adherence (aOR, 1.17; 95% CI, 1.11-1.23) and that patients on newer ASMs were more than three times as likely to be under the care of a neurologist (aOR, 3.26; 95% CI, 3.13-3.41).

The findings draw attention to racial inequities surrounding access to medication and specialists and subspecialists, Dr. Bensken said. Identifying specific barriers and developing solutions is the long-range goal, he added.

“In the interim, increasing the attention to these inequities will, we hope, prompt changes across practices,” Dr. Bensken said.
 

A ‘wake-up call’

Commenting on the findings, Joseph Sirven, MD, professor of neurology at the Mayo Clinic Florida, Jacksonville, said the results were “striking” because newer ASMs are generally the go-to for most physicians who treat epilepsy. 

“Use of first-generation ASMs is typically reserved [for] if one runs out of options,” Dr. Sirven said.

This study and others like it should serve as a “wake-up call” for clinicians, Dr. Sirven added.

“This study is important because it shows that whether we realize it or not, race and ethnicities are playing a role in ASM, and this is related to financial access to newer-generation drugs,” he said. “Similar findings are seen in impoverished countries where first-generation ASM drugs are routinely used because of drug pricing.”
 

More to explore

Also commenting on the study, Scott Mintzer, MD, a professor and director of the Epilepsy Monitoring Unit at Thomas Jefferson University, Philadelphia, said using first-generation ASMs as a proxy for quality of care is “a very innovative concept.”

“From that perspective, the finding that racial minority patients are more likely to be on a first-generation drug is not surprising. But after that it gets far more complicated to interpret,” he added.  

Neither adherence nor care by a neurologist was different in a consistent direction within the various minority populations, Dr. Mintzer noted. In addition, Black patients were as likely to see a neurologist as White patients but still more likely to be on a first-generation drug.

There are also a few caveats to the findings that should be considered, Dr. Mintzer added. First, the sample included only Medicaid recipients, nearly 35% of whom had a comorbid psychosis. Those and other characteristics of the study pool suggest participants aren’t representative of the United States population as a whole. Second, significant shifts in ASM use have occurred since the study data cutoff in 2014, none of which are reflected in these findings.

“So, I don’t think we can really say how to address this yet,” Dr. Mintzer said. “There’s a lot to explore about whether this is still occurring, how generalizable these findings are, and what they might be due to, as there are a host of potential explanations, which the authors themselves acknowledge.”

The study was funded by the U.S. Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities. Dr. Bensken has received support for this work from NIMHD and serves on the Editorial Board of the journal Neurology. Dr. Sirven and Mintzer report no relevant financial relationships.

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

People of color with epilepsy, including Black, Hispanic, and Native Hawaiian and other Pacific Islander patients, are significantly less likely to be prescribed the latest antiseizure medications (ASMs), compared with their White counterparts, new research shows.

Even after controlling for epilepsy severity, comorbid conditions, and other factors that might affect medication choice, researchers found that newer medication use was 29% less likely in Black patients, 23% less likely in Native Hawaiian and other Pacific Islander patients, and 7% less likely in Hispanic patients, compared with White individuals.

“I hope that clinicians will see from our findings that minoritized patients with epilepsy face a myriad of barriers in receiving the highest quality of care, including ASM use,” said lead investigator Wyatt P. Bensken, PhD, adjunct assistant professor of Population and Quantitative Health Sciences at Case Western Reserve University, Cleveland. “Considering your patients’ barriers, and how that influences their care – including ASM selection – will be critical to helping reduce these population-level inequities.”

A prompt for practice change

For the study, researchers used Medicaid claims for more than 78,000 people who had filled at least two prescriptions for an ASM between 2010 and 2014.

Most patients were White (53.4%); 22.6% were Black; 11.9% were Hispanic; 1.6% were Asian; 1.5% were Native Hawaiian or other Pacific Islander; 0.6% American Indian or Alaskan Native; and 8.3% were classified as “other.”

One-quarter of participants were taking an older ASM, such as carbamazepine, phenytoin, and valproate. About 65% were taking second-generation ASMs, including gabapentin, levetiracetam, and zonisamide. A little less than 10% were taking lacosamide, perampenel, or another third-generation ASM.

Compared with White patients, newer medication prescriptions were significantly less likely in Black individuals (adjusted odds ratio, 0.71; 95% confidence interval, 0.68-0.75), Native Hawaiian or other Pacific Islanders (aOR, 0.77; 95% CI, 0.67-0.88), and Hispanic patients (aOR, 0.93; 95% CI, 0.88-0.99).

Third-generation ASMs were used by 10.7% of White patients versus 6% of Black individuals and 5.1% of American Indian or Alaskan Native patients.

Researchers also found that taking a second-generation ASM was associated with better treatment adherence (aOR, 1.17; 95% CI, 1.11-1.23) and that patients on newer ASMs were more than three times as likely to be under the care of a neurologist (aOR, 3.26; 95% CI, 3.13-3.41).

The findings draw attention to racial inequities surrounding access to medication and specialists and subspecialists, Dr. Bensken said. Identifying specific barriers and developing solutions is the long-range goal, he added.

“In the interim, increasing the attention to these inequities will, we hope, prompt changes across practices,” Dr. Bensken said.
 

A ‘wake-up call’

Commenting on the findings, Joseph Sirven, MD, professor of neurology at the Mayo Clinic Florida, Jacksonville, said the results were “striking” because newer ASMs are generally the go-to for most physicians who treat epilepsy. 

“Use of first-generation ASMs is typically reserved [for] if one runs out of options,” Dr. Sirven said.

This study and others like it should serve as a “wake-up call” for clinicians, Dr. Sirven added.

“This study is important because it shows that whether we realize it or not, race and ethnicities are playing a role in ASM, and this is related to financial access to newer-generation drugs,” he said. “Similar findings are seen in impoverished countries where first-generation ASM drugs are routinely used because of drug pricing.”
 

More to explore

Also commenting on the study, Scott Mintzer, MD, a professor and director of the Epilepsy Monitoring Unit at Thomas Jefferson University, Philadelphia, said using first-generation ASMs as a proxy for quality of care is “a very innovative concept.”

“From that perspective, the finding that racial minority patients are more likely to be on a first-generation drug is not surprising. But after that it gets far more complicated to interpret,” he added.  

Neither adherence nor care by a neurologist was different in a consistent direction within the various minority populations, Dr. Mintzer noted. In addition, Black patients were as likely to see a neurologist as White patients but still more likely to be on a first-generation drug.

There are also a few caveats to the findings that should be considered, Dr. Mintzer added. First, the sample included only Medicaid recipients, nearly 35% of whom had a comorbid psychosis. Those and other characteristics of the study pool suggest participants aren’t representative of the United States population as a whole. Second, significant shifts in ASM use have occurred since the study data cutoff in 2014, none of which are reflected in these findings.

“So, I don’t think we can really say how to address this yet,” Dr. Mintzer said. “There’s a lot to explore about whether this is still occurring, how generalizable these findings are, and what they might be due to, as there are a host of potential explanations, which the authors themselves acknowledge.”

The study was funded by the U.S. Centers for Disease Control and Prevention and the National Institute on Minority Health and Health Disparities. Dr. Bensken has received support for this work from NIMHD and serves on the Editorial Board of the journal Neurology. Dr. Sirven and Mintzer report no relevant financial relationships.

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

Adding a modified Atkins diet to standard antiseizure treatments significantly reduces seizure frequency in patients with drug-resistant epilepsy compared with medication alone, new research shows.

In a randomized prospective study, the number of seizures per month dropped by more than half in one-quarter of patients following the high-fat, low-carb diet; and 5% of the group were free from all seizure activity after 6 months.

Both adults and adolescents reported benefits from the diet, which is a less strict version of a traditional ketogenic diet that many patients find difficult to follow. The modified Atkins diet includes foods such as leafy green vegetables and eggs, chicken, fish, bacon, and other animal proteins.

“The use of an exchange list and recipe booklet with local recipes and spices helped in the initiation of modified Atkins diet with the flexibility of meal choices and ease of administration,” said coinvestigator Manjari Tripathi, MD, DM, department of neurology, All India Institute of Medical Science, New Delhi.

“As items were everyday household ingredients in proportion to the requirement of the modified Atkins diet, this diet is possible in low-income countries also,” Dr. Tripathi added.

The findings were published online in the journal Neurology.
 

Low carbs, high benefit

The modified Atkins diet includes around 65% fat, 25% protein, and 10% carbohydrates. Unlike a traditional ketogenic diet, the modified Atkins diet includes no restrictions on protein, calories, or fluids.

Researchers have long known that ketogenic and Atkins diets are associated with reduced seizure activity in adolescents with epilepsy. But previous studies were small, and many were retrospective analyses.

The current investigators enrolled 160 patients (80 adults, 80 adolescents) aged 10-55 years whose epilepsy was not controlled despite using at least three antiseizure medications at maximum tolerated doses.

The intervention group received training in the modified Atkins diet and were given a food exchange list, sample menu, and recipe booklet. Carbohydrate intake was restricted to 20 grams per day.

Participants took supplemental multivitamins and minerals, kept a food diary, logged seizure activity, and measured urine ketone levels three times a day. They also received weekly check-up phone calls to ensure diet adherence.

The control group received a normal diet with no carbohydrate restrictions. All participants continued their prescribed antiseizure therapy throughout the trial.
 

Primary outcome met

The primary study outcome was a reduction in seizures of more than 50%. At 6 months, 26.2% of the intervention group had reached that goal, compared with just 2.5% of the control group (P < .001).

When the median number of seizures in the modified Atkins diet group was analyzed, the frequency dropped in the intervention group from 37.5 per month at baseline to 27.5 per month after 3 months of the modified Atkins diet and to 21.5 per month after 6 months.

Adding the modified Atkins diet had a larger effect on seizure activity in adults than in adolescents. At the end of 6 months, 36% of adolescents on the modified Atkins diet had more than a 50% reduction in seizures, while 57.1% of adults on the diet reached that level.

Quality-of-life scores were also higher in the intervention group.

By the end of the trial, 5% of patients on the modified Atkins diet had no seizure activity at all versus none of the control group. In fact, the median number of seizures increased in the control group during the study.

The mean morning and evening levels of urine ketosis in the intervention group were 58.3 ± 8.0 mg/dL and 62.2 ± 22.6 mg/dL, respectively, suggesting satisfactory diet adherence. There was no significant difference between groups in weight loss.

Dr. Tripathi noted that 33% of participants did not complete the study because of poor tolerance of the diet, lack of benefit, or the inability to follow up – in part due to COVID-19. However, she said tolerance of the modified Atkins diet was better than what has been reported with the ketogenic diet.

“Though the exact mechanism by which such a diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influences the dynamics of the major inhibitory and excitatory neurotransmitter systems in the brain,” Dr. Tripathi said.
 

Benefits outweigh cost

Commenting on the research findings, Mackenzie Cervenka, MD, professor of neurology and director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore, noted that the study is the first randomized controlled trial of this size to demonstrate a benefit from adding the modified Atkins diet to standard antiseizure therapy in treatment-resistant epilepsy.

“Importantly, the study also showed improvement in quality of life and behavior over standard-of-care therapies without significant adverse effects,” said Dr. Cervenka, who was not part of the research.

The investigators noted that the flexibility of the modified Atkins diet allows more variation in menu options and a greater intake of protein, making it easier to follow than a traditional ketogenic diet.

One area of debate, however, is whether these diets are manageable for individuals with low income. Poultry, meat, and fish, all of which are staples of a modified Atkins diet, can be more expensive than other high-carb options such as pasta and rice.

“While some of the foods such as protein sources that patients purchase when they are on a ketogenic diet therapy can be more expensive, if you take into account the cost of antiseizure medications and other antiseizure treatments, hospital visits, and missed work related to seizures, et cetera, the overall financial benefits of seizure reduction with incorporating a ketogenic diet therapy may outweigh these costs,” Dr. Cervenka said.

“There are also low-cost foods that can be used since there is a great deal of flexibility with a modified Atkins diet,” she added.

The study was funded by the Centre of Excellence for Epilepsy, which is funded by the Department of Biotechnology, Government of India. Dr. Tripathi and Dr. Cervenka report no relevant financial relationships.

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

Adding a modified Atkins diet to standard antiseizure treatments significantly reduces seizure frequency in patients with drug-resistant epilepsy compared with medication alone, new research shows.

In a randomized prospective study, the number of seizures per month dropped by more than half in one-quarter of patients following the high-fat, low-carb diet; and 5% of the group were free from all seizure activity after 6 months.

Both adults and adolescents reported benefits from the diet, which is a less strict version of a traditional ketogenic diet that many patients find difficult to follow. The modified Atkins diet includes foods such as leafy green vegetables and eggs, chicken, fish, bacon, and other animal proteins.

“The use of an exchange list and recipe booklet with local recipes and spices helped in the initiation of modified Atkins diet with the flexibility of meal choices and ease of administration,” said coinvestigator Manjari Tripathi, MD, DM, department of neurology, All India Institute of Medical Science, New Delhi.

“As items were everyday household ingredients in proportion to the requirement of the modified Atkins diet, this diet is possible in low-income countries also,” Dr. Tripathi added.

The findings were published online in the journal Neurology.
 

Low carbs, high benefit

The modified Atkins diet includes around 65% fat, 25% protein, and 10% carbohydrates. Unlike a traditional ketogenic diet, the modified Atkins diet includes no restrictions on protein, calories, or fluids.

Researchers have long known that ketogenic and Atkins diets are associated with reduced seizure activity in adolescents with epilepsy. But previous studies were small, and many were retrospective analyses.

The current investigators enrolled 160 patients (80 adults, 80 adolescents) aged 10-55 years whose epilepsy was not controlled despite using at least three antiseizure medications at maximum tolerated doses.

The intervention group received training in the modified Atkins diet and were given a food exchange list, sample menu, and recipe booklet. Carbohydrate intake was restricted to 20 grams per day.

Participants took supplemental multivitamins and minerals, kept a food diary, logged seizure activity, and measured urine ketone levels three times a day. They also received weekly check-up phone calls to ensure diet adherence.

The control group received a normal diet with no carbohydrate restrictions. All participants continued their prescribed antiseizure therapy throughout the trial.
 

Primary outcome met

The primary study outcome was a reduction in seizures of more than 50%. At 6 months, 26.2% of the intervention group had reached that goal, compared with just 2.5% of the control group (P < .001).

When the median number of seizures in the modified Atkins diet group was analyzed, the frequency dropped in the intervention group from 37.5 per month at baseline to 27.5 per month after 3 months of the modified Atkins diet and to 21.5 per month after 6 months.

Adding the modified Atkins diet had a larger effect on seizure activity in adults than in adolescents. At the end of 6 months, 36% of adolescents on the modified Atkins diet had more than a 50% reduction in seizures, while 57.1% of adults on the diet reached that level.

Quality-of-life scores were also higher in the intervention group.

By the end of the trial, 5% of patients on the modified Atkins diet had no seizure activity at all versus none of the control group. In fact, the median number of seizures increased in the control group during the study.

The mean morning and evening levels of urine ketosis in the intervention group were 58.3 ± 8.0 mg/dL and 62.2 ± 22.6 mg/dL, respectively, suggesting satisfactory diet adherence. There was no significant difference between groups in weight loss.

Dr. Tripathi noted that 33% of participants did not complete the study because of poor tolerance of the diet, lack of benefit, or the inability to follow up – in part due to COVID-19. However, she said tolerance of the modified Atkins diet was better than what has been reported with the ketogenic diet.

“Though the exact mechanism by which such a diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influences the dynamics of the major inhibitory and excitatory neurotransmitter systems in the brain,” Dr. Tripathi said.
 

Benefits outweigh cost

Commenting on the research findings, Mackenzie Cervenka, MD, professor of neurology and director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore, noted that the study is the first randomized controlled trial of this size to demonstrate a benefit from adding the modified Atkins diet to standard antiseizure therapy in treatment-resistant epilepsy.

“Importantly, the study also showed improvement in quality of life and behavior over standard-of-care therapies without significant adverse effects,” said Dr. Cervenka, who was not part of the research.

The investigators noted that the flexibility of the modified Atkins diet allows more variation in menu options and a greater intake of protein, making it easier to follow than a traditional ketogenic diet.

One area of debate, however, is whether these diets are manageable for individuals with low income. Poultry, meat, and fish, all of which are staples of a modified Atkins diet, can be more expensive than other high-carb options such as pasta and rice.

“While some of the foods such as protein sources that patients purchase when they are on a ketogenic diet therapy can be more expensive, if you take into account the cost of antiseizure medications and other antiseizure treatments, hospital visits, and missed work related to seizures, et cetera, the overall financial benefits of seizure reduction with incorporating a ketogenic diet therapy may outweigh these costs,” Dr. Cervenka said.

“There are also low-cost foods that can be used since there is a great deal of flexibility with a modified Atkins diet,” she added.

The study was funded by the Centre of Excellence for Epilepsy, which is funded by the Department of Biotechnology, Government of India. Dr. Tripathi and Dr. Cervenka report no relevant financial relationships.

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

Adding a modified Atkins diet to standard antiseizure treatments significantly reduces seizure frequency in patients with drug-resistant epilepsy compared with medication alone, new research shows.

In a randomized prospective study, the number of seizures per month dropped by more than half in one-quarter of patients following the high-fat, low-carb diet; and 5% of the group were free from all seizure activity after 6 months.

Both adults and adolescents reported benefits from the diet, which is a less strict version of a traditional ketogenic diet that many patients find difficult to follow. The modified Atkins diet includes foods such as leafy green vegetables and eggs, chicken, fish, bacon, and other animal proteins.

“The use of an exchange list and recipe booklet with local recipes and spices helped in the initiation of modified Atkins diet with the flexibility of meal choices and ease of administration,” said coinvestigator Manjari Tripathi, MD, DM, department of neurology, All India Institute of Medical Science, New Delhi.

“As items were everyday household ingredients in proportion to the requirement of the modified Atkins diet, this diet is possible in low-income countries also,” Dr. Tripathi added.

The findings were published online in the journal Neurology.
 

Low carbs, high benefit

The modified Atkins diet includes around 65% fat, 25% protein, and 10% carbohydrates. Unlike a traditional ketogenic diet, the modified Atkins diet includes no restrictions on protein, calories, or fluids.

Researchers have long known that ketogenic and Atkins diets are associated with reduced seizure activity in adolescents with epilepsy. But previous studies were small, and many were retrospective analyses.

The current investigators enrolled 160 patients (80 adults, 80 adolescents) aged 10-55 years whose epilepsy was not controlled despite using at least three antiseizure medications at maximum tolerated doses.

The intervention group received training in the modified Atkins diet and were given a food exchange list, sample menu, and recipe booklet. Carbohydrate intake was restricted to 20 grams per day.

Participants took supplemental multivitamins and minerals, kept a food diary, logged seizure activity, and measured urine ketone levels three times a day. They also received weekly check-up phone calls to ensure diet adherence.

The control group received a normal diet with no carbohydrate restrictions. All participants continued their prescribed antiseizure therapy throughout the trial.
 

Primary outcome met

The primary study outcome was a reduction in seizures of more than 50%. At 6 months, 26.2% of the intervention group had reached that goal, compared with just 2.5% of the control group (P < .001).

When the median number of seizures in the modified Atkins diet group was analyzed, the frequency dropped in the intervention group from 37.5 per month at baseline to 27.5 per month after 3 months of the modified Atkins diet and to 21.5 per month after 6 months.

Adding the modified Atkins diet had a larger effect on seizure activity in adults than in adolescents. At the end of 6 months, 36% of adolescents on the modified Atkins diet had more than a 50% reduction in seizures, while 57.1% of adults on the diet reached that level.

Quality-of-life scores were also higher in the intervention group.

By the end of the trial, 5% of patients on the modified Atkins diet had no seizure activity at all versus none of the control group. In fact, the median number of seizures increased in the control group during the study.

The mean morning and evening levels of urine ketosis in the intervention group were 58.3 ± 8.0 mg/dL and 62.2 ± 22.6 mg/dL, respectively, suggesting satisfactory diet adherence. There was no significant difference between groups in weight loss.

Dr. Tripathi noted that 33% of participants did not complete the study because of poor tolerance of the diet, lack of benefit, or the inability to follow up – in part due to COVID-19. However, she said tolerance of the modified Atkins diet was better than what has been reported with the ketogenic diet.

“Though the exact mechanism by which such a diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influences the dynamics of the major inhibitory and excitatory neurotransmitter systems in the brain,” Dr. Tripathi said.
 

Benefits outweigh cost

Commenting on the research findings, Mackenzie Cervenka, MD, professor of neurology and director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore, noted that the study is the first randomized controlled trial of this size to demonstrate a benefit from adding the modified Atkins diet to standard antiseizure therapy in treatment-resistant epilepsy.

“Importantly, the study also showed improvement in quality of life and behavior over standard-of-care therapies without significant adverse effects,” said Dr. Cervenka, who was not part of the research.

The investigators noted that the flexibility of the modified Atkins diet allows more variation in menu options and a greater intake of protein, making it easier to follow than a traditional ketogenic diet.

One area of debate, however, is whether these diets are manageable for individuals with low income. Poultry, meat, and fish, all of which are staples of a modified Atkins diet, can be more expensive than other high-carb options such as pasta and rice.

“While some of the foods such as protein sources that patients purchase when they are on a ketogenic diet therapy can be more expensive, if you take into account the cost of antiseizure medications and other antiseizure treatments, hospital visits, and missed work related to seizures, et cetera, the overall financial benefits of seizure reduction with incorporating a ketogenic diet therapy may outweigh these costs,” Dr. Cervenka said.

“There are also low-cost foods that can be used since there is a great deal of flexibility with a modified Atkins diet,” she added.

The study was funded by the Centre of Excellence for Epilepsy, which is funded by the Department of Biotechnology, Government of India. Dr. Tripathi and Dr. Cervenka report no relevant financial relationships.

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

Antiepileptic drugs (AEDs) are linked to an increased risk of Parkinson’s disease, new research suggests.

Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.

“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.

“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.

He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”

The study was published online in JAMA Neurology.
 

Plausible, but unclear link

Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.

It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.

“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
 

Are AEDs the culprit?

The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.

The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).

Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.

The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.

Alternative explanations

Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”

Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.

For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”

Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.

“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.

She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”

For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.

The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.

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

Antiepileptic drugs (AEDs) are linked to an increased risk of Parkinson’s disease, new research suggests.

Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.

“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.

“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.

He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”

The study was published online in JAMA Neurology.
 

Plausible, but unclear link

Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.

It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.

“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
 

Are AEDs the culprit?

The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.

The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).

Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.

The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.

Alternative explanations

Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”

Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.

For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”

Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.

“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.

She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”

For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.

The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.

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

Antiepileptic drugs (AEDs) are linked to an increased risk of Parkinson’s disease, new research suggests.

Drawing on data from the UK Biobank, investigators compared more than 1,400 individuals diagnosed with Parkinson’s disease with matched control persons and found a considerably higher risk of developing Parkinson’s disease among those who had taken AEDs in comparison with those who had not. There was a trend linking a greater number of AED prescriptions and multiple AEDs associated with a greater risk for Parkinson’s disease.

“We observed an association between the most commonly prescribed antiepileptic drugs in the U.K. and Parkinson’s disease using data from UK Biobank,” said senior author Alastair Noyce, PhD, professor of neurology and neuroepidemiology and honorary consultant neurologist, Queen Mary University of London.

“This is the first time that a comprehensive study of the link between AEDs and Parkinson’s disease has been undertaken,” said Dr. Noyce.

He added that the findings have no immediate clinical implications, “but further research is definitely needed, [as] this is an interesting observation made in a research setting.”

The study was published online in JAMA Neurology.
 

Plausible, but unclear link

Recent observational studies have found a “temporal association” between epilepsy and incident Parkinson’s disease, but the mechanism underlying this association is “unclear,” the authors wrote.

It is “plausible” that AEDs “may account for some or all of the apparent association between epilepsy and Parkinson’s disease” and that movement disorders are potential side effects of AEDs, but the association between AEDs and Parkinson’s disease has “not been well studied,” so it remains “unclear” whether AEDs play a role in the association.

“We have previously reported an association between epilepsy and Parkinson’s disease in several different datasets. Here, we wanted to see if it could be explained by an association with the drugs used to treat epilepsy rather than epilepsy per se,” Dr. Noyce explained.
 

Are AEDs the culprit?

The researchers used data from the UK Biobank, a longitudinal cohort study with more than 500,000 participants, as well as linked primary care medication data to conduct a nested case-control study to investigate this potential association. Participants ranged in age from 40 to 69 years and were recruited between 2006 and 2010.

The researchers compared 1,433 individuals diagnosed with Parkinson’s disease with 8,598 control persons who were matched in a 6:1 ratio for age, sex, race, ethnicity, and socioeconomic status (median [interquartile range] age, 71 [65-75] years; 60.9% men; 97.5% White).

Of those with Parkinson’s disease, 4.3% had been prescribed an AED prior to the date of their being diagnosed with Parkinson’s disease, compared with 2.5% in the control group; 4.4% had been diagnosed with epilepsy, compared with 1% of the control persons.

The strongest evidence was for the association between lamotrigine, levetiracetam, and sodium valproate and Parkinson’s disease. There was “weaker evidence” for carbamazepine, although all the AEDs were associated with a higher risk of Parkinson’s disease.

Alternative explanations

Commenting on the research, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, said, “It has been established in prior research that there is an association between epilepsy and Parkinson’s disease.” The current study “shows that having had a prescription written for one of four antiepileptic medications was associated with subsequently receiving a diagnosis of Parkinson’s disease.”

Although one possible conclusion is that the AEDs themselves increase the risk of developing Parkinson’s disease, “there seem to be other alternative explanations as to why a person who had been prescribed AEDs has an increased risk of receiving a diagnosis of Parkinson’s disease,” said Dr. Gilbert, an associate professor of neurology at Bellevue Hospital Center, New York, who was not involved with the current study.

For example, pre-motor changes in the brain of persons with Parkinson’s disease “may increase the risk of requiring an AED by potentially increasing the risk of having a seizure,” and “changes in the brain caused by the seizures for which AEDs are prescribed may increase the risk of Parkinson’s disease.”

Moreover, psychiatric changes related to Parkinson’s disease may have led to the prescription for AEDs, because at least two of the AEDs are also prescribed for mood stabilization, Dr. Gilbert suggested.

“An unanswered question that the paper acknowledges is, what about people who receive AEDs for reasons other than seizures? Do they also have an increased risk of Parkinson’s disease? This would be an interesting population to focus on because it would remove the link between AEDs and seizure and focus on the association between AEDs and Parkinson’s disease,” Dr. Gilbert said.

She emphasized that people who take AEDs for seizures “should not jump to the conclusion that they must come off these medications so as not to increase their risk of developing Parkinson’s disease.” She noted that having seizures “can be dangerous – injuries can occur during a seizure, and if a seizure can’t be stopped or a number occur in rapid succession, brain injury may result.”

For these reasons, people with “a tendency to have seizures need to protect themselves with AEDs” and “should certainly reach out to their neurologists with any questions,” Dr. Gilbert said.

The Preventive Neurology Unit is funded by Barts Charity. The Apocrita High Performance Cluster facility, supported by Queen Mary University London Research–IT Services, was used for this research. Dr. Noyce has received grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. The other authors’ disclosures are listed on the original article. Dr. Gilbert reports no relevant financial relationships.

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

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.

In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that carbamazepine, oxcarbazepine, and topiramate were associated with low birth weight and increased risk of infants being born small for gestational age.

• Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
• Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
• Topiramate, 1.60 (95% CI, 1.15-2.24).
• Pregabalin, 1.23 (95% CI, 1.02-1.48).
• Clobazam, 4.36 (95% CI, 1.66-11.45).

The odds ratios for being born small for gestational age were:

• Carbamazepine, 1.25 (95% CI, 1.11-1.41).
• Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
• Topiramate, 1.52 (95% CI, 1.20-1.91).

“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.

He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
 

Use with caution

This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.

“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”

She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.

The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.

NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.

In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that carbamazepine, oxcarbazepine, and topiramate were associated with low birth weight and increased risk of infants being born small for gestational age.

• Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
• Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
• Topiramate, 1.60 (95% CI, 1.15-2.24).
• Pregabalin, 1.23 (95% CI, 1.02-1.48).
• Clobazam, 4.36 (95% CI, 1.66-11.45).

The odds ratios for being born small for gestational age were:

• Carbamazepine, 1.25 (95% CI, 1.11-1.41).
• Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
• Topiramate, 1.52 (95% CI, 1.20-1.91).

“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.

He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
 

Use with caution

This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.

“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”

She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.

The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.

NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.

In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that carbamazepine, oxcarbazepine, and topiramate were associated with low birth weight and increased risk of infants being born small for gestational age.

• Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
• Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
• Topiramate, 1.60 (95% CI, 1.15-2.24).
• Pregabalin, 1.23 (95% CI, 1.02-1.48).
• Clobazam, 4.36 (95% CI, 1.66-11.45).

The odds ratios for being born small for gestational age were:

• Carbamazepine, 1.25 (95% CI, 1.11-1.41).
• Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
• Topiramate, 1.52 (95% CI, 1.20-1.91).

“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.

He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
 

Use with caution

This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.

“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”

She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.

The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

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

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

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

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

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

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

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

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

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

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

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

NASHVILLE, Tenn. – New research shows stark racial and ethnic discrepancies in health care outcomes for patients with status epilepticus. Investigators found that among Black patients with status epilepticus, the hospitalization rate was twice that of their White counterparts. Other findings reveal age and income disparities.

“The results suggest that racial minorities, those with a lower income, and the elderly are an appropriate target to improve health outcomes and reduce health inequality,” said Gabriela Tantillo Sepúlveda, MD, assistant professor of neurology, Baylor College of Medicine, Houston.

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

An examination of outcomes

Status epilepticus is associated with high rates of morbidity and mortality. Disparities in epilepsy care have previously been described, but little attention has been paid to the contribution of disparities to status epilepticus care and associated outcomes.

Researchers used 2010-2019 data from the Nationwide Inpatient Sample, a database covering a cross-section of hospitalizations in 48 states and the District of Columbia. From relevant diagnostic codes, they calculated status epilepticus prevalence as the rate per 10,000 hospitalizations and stratified this by demographics.

Over the study period, investigators identified 486,861 status epilepticus hospitalizations, most (71.3%) at urban teaching hospitals.

Status epilepticus prevalence was highest for non-Hispanic Black patients, at 27.3, followed by non-Hispanic others, at 16.1, Hispanic patients, at 15.8, and non-Hispanic-White patients, at 13.7 (P < .01).

The finding that Black patients had double the rate as White patients was “definitely surprising,” said Dr. Tantillo Sepúlveda.

Research over the past 20 years revealed similar disparities related to status epilepticus, “so it’s upsetting that these disparities have persisted. Unfortunately, we still have a lot of work to do to reduce health inequalities,” she said.

The investigators found that the prevalence of status epilepticus was higher in the lowest-income quartile, compared with the highest (18.7 vs. 14; P < .01).
 

Need for physician advocacy

Unlike previous studies, this research assessed various interventions in different age groups and showed that the likelihood of intubation, tracheostomy, gastrostomy, and in-hospital mortality increased with age.

For example, compared with the reference group (patients aged 18-39 years), the odds of intubation were 1.22 (95% confidence interval, 1.16-1.27) for those aged 40-59 years and 1.48 (95% CI, 1.42-1.54) for those aged 60-79. Those aged 80 and older were most likely to be intubated, at an odds ratio of 1.5 (95% CI, 1.43-1.58).

Elderly patients were most likely to undergo tracheostomy (OR, 2.0; 95% CI, 1.75-2.27), gastrostomy (OR, 3.37; 95% CI, 2.97-3.83), and to experience in-hospital mortality (OR, 6.51; 95% CI, 5.95-7.13), compared with the youngest patients.

These intervention rates also varied by racial/ethnic groups. Minority populations, particularly Black people, had higher odds of tracheostomy and gastrostomy, compared with non-Hispanic White persons.

The odds of undergoing electroencephalography monitoring progressively rose as income level increased (OR, 1.47; 95% CI, 1.34-1.62) for the highest income quartile versus the lowest quartile. The odds of undergoing EEG monitoring were also higher at urban teaching hospitals than at rural hospitals.

Tackling these disparities in this patient population include increasing resources, personnel, and health education aimed at minorities, low-income patients, and the elderly, said Dr. Tantillo Sepúlveda. She added that more research is needed “to determine the most effective ways of accomplishing this goal.”

The medical community can help reduce disparities, said Dr. Tantillo Sepúlveda, by working to improve health literacy, to reduce stigma associated with seizures, and to increase awareness of seizure risk factors.

They can also work to expand access to outpatient neurology clinics, epilepsy monitoring units, and epilepsy surgery. “Ethnic and racial minorities are less likely to receive epilepsy surgery for temporal lobe epilepsy, which has been shown to improve quality of life and reduce seizure burden,” Dr. Tantillo Sepúlveda noted.
 

Across-the-board problem

Commenting on the research, Daniel Lowenstein, MD, professor of neurology, University of California, San Francisco, said the findings aren’t at all surprising. “It’s yet another piece of evidence on what has now become a rather voluminous literature that documents the very significant disparities that exist in our health care system,” said Dr. Lowenstein. “There’s just a huge literature on ‘name your disease and you’ll see the disparities.’ ”

Disparities exist, for example, in diagnosing breast cancer and prostate cancer, in the treatment of stroke and in related outcomes, and there is a well-documented “big disparity” in the approach to pain control among patients presenting at the emergency department, said Dr. Lowenstein.

However, he doesn’t know how disparities in epilepsy and specifically in status epilepticus, compared with disparities regarding other diseases and disorders. He noted that in the case of epilepsy, the situation is likely exacerbated by the stigma associated with that disease.

Dr. Lowenstein agreed that clinicians should play a role in reversing disparities. “We as physicians have a responsibility to be a voice for change in our health care system.”

The study was supported by the Center of Excellence for health equity, training, and research at the Baylor College of Medicine. Dr. Tantillo Sepúlveda and Dr. Lowenstein report no relevant financial relationships.

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

NASHVILLE, Tenn. – New research shows stark racial and ethnic discrepancies in health care outcomes for patients with status epilepticus. Investigators found that among Black patients with status epilepticus, the hospitalization rate was twice that of their White counterparts. Other findings reveal age and income disparities.

“The results suggest that racial minorities, those with a lower income, and the elderly are an appropriate target to improve health outcomes and reduce health inequality,” said Gabriela Tantillo Sepúlveda, MD, assistant professor of neurology, Baylor College of Medicine, Houston.

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

An examination of outcomes

Status epilepticus is associated with high rates of morbidity and mortality. Disparities in epilepsy care have previously been described, but little attention has been paid to the contribution of disparities to status epilepticus care and associated outcomes.

Researchers used 2010-2019 data from the Nationwide Inpatient Sample, a database covering a cross-section of hospitalizations in 48 states and the District of Columbia. From relevant diagnostic codes, they calculated status epilepticus prevalence as the rate per 10,000 hospitalizations and stratified this by demographics.

Over the study period, investigators identified 486,861 status epilepticus hospitalizations, most (71.3%) at urban teaching hospitals.

Status epilepticus prevalence was highest for non-Hispanic Black patients, at 27.3, followed by non-Hispanic others, at 16.1, Hispanic patients, at 15.8, and non-Hispanic-White patients, at 13.7 (P < .01).

The finding that Black patients had double the rate as White patients was “definitely surprising,” said Dr. Tantillo Sepúlveda.

Research over the past 20 years revealed similar disparities related to status epilepticus, “so it’s upsetting that these disparities have persisted. Unfortunately, we still have a lot of work to do to reduce health inequalities,” she said.

The investigators found that the prevalence of status epilepticus was higher in the lowest-income quartile, compared with the highest (18.7 vs. 14; P < .01).
 

Need for physician advocacy

Unlike previous studies, this research assessed various interventions in different age groups and showed that the likelihood of intubation, tracheostomy, gastrostomy, and in-hospital mortality increased with age.

For example, compared with the reference group (patients aged 18-39 years), the odds of intubation were 1.22 (95% confidence interval, 1.16-1.27) for those aged 40-59 years and 1.48 (95% CI, 1.42-1.54) for those aged 60-79. Those aged 80 and older were most likely to be intubated, at an odds ratio of 1.5 (95% CI, 1.43-1.58).

Elderly patients were most likely to undergo tracheostomy (OR, 2.0; 95% CI, 1.75-2.27), gastrostomy (OR, 3.37; 95% CI, 2.97-3.83), and to experience in-hospital mortality (OR, 6.51; 95% CI, 5.95-7.13), compared with the youngest patients.

These intervention rates also varied by racial/ethnic groups. Minority populations, particularly Black people, had higher odds of tracheostomy and gastrostomy, compared with non-Hispanic White persons.

The odds of undergoing electroencephalography monitoring progressively rose as income level increased (OR, 1.47; 95% CI, 1.34-1.62) for the highest income quartile versus the lowest quartile. The odds of undergoing EEG monitoring were also higher at urban teaching hospitals than at rural hospitals.

Tackling these disparities in this patient population include increasing resources, personnel, and health education aimed at minorities, low-income patients, and the elderly, said Dr. Tantillo Sepúlveda. She added that more research is needed “to determine the most effective ways of accomplishing this goal.”

The medical community can help reduce disparities, said Dr. Tantillo Sepúlveda, by working to improve health literacy, to reduce stigma associated with seizures, and to increase awareness of seizure risk factors.

They can also work to expand access to outpatient neurology clinics, epilepsy monitoring units, and epilepsy surgery. “Ethnic and racial minorities are less likely to receive epilepsy surgery for temporal lobe epilepsy, which has been shown to improve quality of life and reduce seizure burden,” Dr. Tantillo Sepúlveda noted.
 

Across-the-board problem

Commenting on the research, Daniel Lowenstein, MD, professor of neurology, University of California, San Francisco, said the findings aren’t at all surprising. “It’s yet another piece of evidence on what has now become a rather voluminous literature that documents the very significant disparities that exist in our health care system,” said Dr. Lowenstein. “There’s just a huge literature on ‘name your disease and you’ll see the disparities.’ ”

Disparities exist, for example, in diagnosing breast cancer and prostate cancer, in the treatment of stroke and in related outcomes, and there is a well-documented “big disparity” in the approach to pain control among patients presenting at the emergency department, said Dr. Lowenstein.

However, he doesn’t know how disparities in epilepsy and specifically in status epilepticus, compared with disparities regarding other diseases and disorders. He noted that in the case of epilepsy, the situation is likely exacerbated by the stigma associated with that disease.

Dr. Lowenstein agreed that clinicians should play a role in reversing disparities. “We as physicians have a responsibility to be a voice for change in our health care system.”

The study was supported by the Center of Excellence for health equity, training, and research at the Baylor College of Medicine. Dr. Tantillo Sepúlveda and Dr. Lowenstein report no relevant financial relationships.

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

NASHVILLE, Tenn. – New research shows stark racial and ethnic discrepancies in health care outcomes for patients with status epilepticus. Investigators found that among Black patients with status epilepticus, the hospitalization rate was twice that of their White counterparts. Other findings reveal age and income disparities.

“The results suggest that racial minorities, those with a lower income, and the elderly are an appropriate target to improve health outcomes and reduce health inequality,” said Gabriela Tantillo Sepúlveda, MD, assistant professor of neurology, Baylor College of Medicine, Houston.

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

An examination of outcomes

Status epilepticus is associated with high rates of morbidity and mortality. Disparities in epilepsy care have previously been described, but little attention has been paid to the contribution of disparities to status epilepticus care and associated outcomes.

Researchers used 2010-2019 data from the Nationwide Inpatient Sample, a database covering a cross-section of hospitalizations in 48 states and the District of Columbia. From relevant diagnostic codes, they calculated status epilepticus prevalence as the rate per 10,000 hospitalizations and stratified this by demographics.

Over the study period, investigators identified 486,861 status epilepticus hospitalizations, most (71.3%) at urban teaching hospitals.

Status epilepticus prevalence was highest for non-Hispanic Black patients, at 27.3, followed by non-Hispanic others, at 16.1, Hispanic patients, at 15.8, and non-Hispanic-White patients, at 13.7 (P < .01).

The finding that Black patients had double the rate as White patients was “definitely surprising,” said Dr. Tantillo Sepúlveda.

Research over the past 20 years revealed similar disparities related to status epilepticus, “so it’s upsetting that these disparities have persisted. Unfortunately, we still have a lot of work to do to reduce health inequalities,” she said.

The investigators found that the prevalence of status epilepticus was higher in the lowest-income quartile, compared with the highest (18.7 vs. 14; P < .01).
 

Need for physician advocacy

Unlike previous studies, this research assessed various interventions in different age groups and showed that the likelihood of intubation, tracheostomy, gastrostomy, and in-hospital mortality increased with age.

For example, compared with the reference group (patients aged 18-39 years), the odds of intubation were 1.22 (95% confidence interval, 1.16-1.27) for those aged 40-59 years and 1.48 (95% CI, 1.42-1.54) for those aged 60-79. Those aged 80 and older were most likely to be intubated, at an odds ratio of 1.5 (95% CI, 1.43-1.58).

Elderly patients were most likely to undergo tracheostomy (OR, 2.0; 95% CI, 1.75-2.27), gastrostomy (OR, 3.37; 95% CI, 2.97-3.83), and to experience in-hospital mortality (OR, 6.51; 95% CI, 5.95-7.13), compared with the youngest patients.

These intervention rates also varied by racial/ethnic groups. Minority populations, particularly Black people, had higher odds of tracheostomy and gastrostomy, compared with non-Hispanic White persons.

The odds of undergoing electroencephalography monitoring progressively rose as income level increased (OR, 1.47; 95% CI, 1.34-1.62) for the highest income quartile versus the lowest quartile. The odds of undergoing EEG monitoring were also higher at urban teaching hospitals than at rural hospitals.

Tackling these disparities in this patient population include increasing resources, personnel, and health education aimed at minorities, low-income patients, and the elderly, said Dr. Tantillo Sepúlveda. She added that more research is needed “to determine the most effective ways of accomplishing this goal.”

The medical community can help reduce disparities, said Dr. Tantillo Sepúlveda, by working to improve health literacy, to reduce stigma associated with seizures, and to increase awareness of seizure risk factors.

They can also work to expand access to outpatient neurology clinics, epilepsy monitoring units, and epilepsy surgery. “Ethnic and racial minorities are less likely to receive epilepsy surgery for temporal lobe epilepsy, which has been shown to improve quality of life and reduce seizure burden,” Dr. Tantillo Sepúlveda noted.
 

Across-the-board problem

Commenting on the research, Daniel Lowenstein, MD, professor of neurology, University of California, San Francisco, said the findings aren’t at all surprising. “It’s yet another piece of evidence on what has now become a rather voluminous literature that documents the very significant disparities that exist in our health care system,” said Dr. Lowenstein. “There’s just a huge literature on ‘name your disease and you’ll see the disparities.’ ”

Disparities exist, for example, in diagnosing breast cancer and prostate cancer, in the treatment of stroke and in related outcomes, and there is a well-documented “big disparity” in the approach to pain control among patients presenting at the emergency department, said Dr. Lowenstein.

However, he doesn’t know how disparities in epilepsy and specifically in status epilepticus, compared with disparities regarding other diseases and disorders. He noted that in the case of epilepsy, the situation is likely exacerbated by the stigma associated with that disease.

Dr. Lowenstein agreed that clinicians should play a role in reversing disparities. “We as physicians have a responsibility to be a voice for change in our health care system.”

The study was supported by the Center of Excellence for health equity, training, and research at the Baylor College of Medicine. Dr. Tantillo Sepúlveda and Dr. Lowenstein report no relevant financial relationships.

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