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More reassurance for certain antiseizure drugs in pregnancy
Further evidence supporting the safety of two antiseizure medications in pregnancy has come from a new study. Most of the women with epilepsy in the study took either lamotrigine or levetiracetam, or a combination of the two, during their pregnancy.
However, a secondary analysis suggested a possible signal of exposure-dependent effects on child outcomes – worse outcomes with higher exposure levels – with levetiracetam.
The results were presented at the American Academy of Neurology’s 2021 annual meeting.
Additional reassurance
“Our new study adds confidence to the use of lamotrigine and levetiracetam during pregnancy, adding larger numbers with a new cohort. In addition, it provides some preliminary data on some of the other new antiseizure medications, and it is the first study to address the effects of clearance in pregnancy to better assess exposure,” said lead investigator, Kimford J. Meador, MD. “Overall, I am reassured by this data, but there is still a lot that is unknown,” he added.
“Our main results show no difference in verbal index or general conceptual ability scores in children born to women with epilepsy compared to children born to healthy women. This is a big positive message,” Dr. Meador said.
In terms of secondary analysis focusing on exposure levels (dose and blood levels of antiseizure medications), there was no overall signal of harm when looking at the whole group, but when the researchers analyzed the data on individual drugs, they found a “slight signal” toward reduced verbal index scores with increasing exposure levels with levetiracetam. No differences were seen on general conceptual ability.
“In the secondary analysis, there was a marginal signal for exposure levels with levetiracetam, with increased blood levels of the drug associated with reduced verbal index scores,” reported Dr. Meador, professor of neurology and neurological sciences at Stanford (Calif.) University. “We saw some signal in the children when they were 2 years old, and this was still there but not as striking at 3 years old.”
He said these secondary results should be interpreted with extreme caution. “We don’t want to overemphasize these secondary findings, as the primary outcome showed no difference, and there was no effect on exposure levels when looking at all the drugs together. I don’t want to oversimplify this, as I am still not sure whether this is a real association or not,” Dr. Meador commented.
He explained that conducting neurobehavioral tests on 2- and 3-year-olds was very difficult. “It is more of an art form than science, and as the children get older these signals often dissipate. We will know more by the time they are 6, when these tests become easier to conduct,” he said. He also noted that the results would need to be replicated in a different cohort.
“I don’t think these results would change how we manage women during pregnancy in terms of using levetiracetam. It is still a safe drug during pregnancy,” Dr. Meador said.
He pointed out that data on safety in pregnancy is only available for very few antiseizure drugs. “There are over 30 antiseizure medications, but we have adequate data in pregnancy on only a handful. We have data suggesting lamotrigine, levetiracetam, and carbamazepine appear to be relatively safe, and evidence showing phenobarbital and valproate are not safe.”
Antiseizure medications as a class are among the most commonly prescribed teratogenic drugs given to women of childbearing age, Dr. Meador noted. They are used not only for epilepsy but also for many other psychiatric and pain indications, so these results are applicable to quite a broad population, he added.
He pointed out that previous studies did not assess exposure using blood levels, which is important, as clearance of drug increases during pregnancy but varies across antiseizure medications and across individuals on the same drug. “Thus, it is unclear if these changes could obscure exposure-dependent effects. Our present studies assessed blood levels to better measure fetal exposure.”
Advice for pregnant patients with epilepsy
Dr. Meador explained that risk for adverse effects with antiseizure medication always needs to be balanced with risk for seizures if the medication was not used.
“In women planning a pregnancy, we recommend that they plan ahead with their physician to try and use the safest antiseizure medication and gain good control beforehand and then maintain the same blood levels of whichever drug is being used during pregnancy,” Dr. Meador said. “At present, lamotrigine and levetiracetam are the two safest drugs to use in pregnancy. They both look generally very safe compared with some other epilepsy drugs – such as valproate, which poses a serious risk to cognitive and behavioral development.”
He also advised that women should be taking folic acid regularly, as this has been shown to be related to improved cognitive and behavioral outcomes. “Since half of pregnancies are not planned, it is important to take these actions before pregnancy,” he added.
The current study involved 289 women with epilepsy and 89 women without epilepsy, all of whom enrolled in the study during pregnancy. Use of antiseizure medications was recorded. Of the women with epilepsy, 74% were on monotherapy, with 43% on lamotrigine and 37% on levetiracetam. There were 4% who took no drug and 22% took more than one drug. Of those who took more than one drug, close to half took a combination of lamotrigine and levetiracetam. Levels of medications in the blood of the women with epilepsy were measured in the third trimester.
Assessment of neurobehavioral development
For the current analysis, the children were evaluated at age 3 with a series of cognitive and developmental tests that measured vocabulary, listening comprehension, number recall, and pattern recognition, and results were adjusted for mother’s IQ, education level, age at enrollment, postbirth average BAI (Beck Anxiety Inventory score), and child’s ethnicity, sex, and breastfeeding status.
The primary outcome showed that verbal Index scores at age 3 did not differ for children of women with epilepsy versus those for children of women without epilepsy (LS mean 102.7 vs. 102.1).
Antiseizure medication exposure as evident by the maximum third trimester blood levels was not related to verbal index scores (n = 265; adjusted parameter estimate, -1.9; 95% confidence interval, -6.8 to 3.1).
General conceptual ability scores also did not differ between the two groups: 105.1 for children of women with epilepsy versus 103.5 for children of healthy women.
In terms of exposure levels, the third trimester maximum observed ratio of antiseizure medication blood levels was not significantly associated with adjusted general conceptual ability scores for children of women with epilepsy; neither were monotherapies or polytherapies evaluated separately, Dr. Meador reported.
However, when the verbal index scores for the main antiepileptic drug groups were analyzed separately, exposure level to levetiracetam was the only one that was significant, with a P value of .028. But Dr. Meador again stressed that this finding should be interpreted with caution given that it is a secondary exploratory analysis without control for multiple comparisons.
The researchers plan to assess these children at older ages where evaluations are more sensitive to ultimate outcomes.
“Information on use in pregnancy for most antiseizure medications is still unknown, so further studies to assess risks for the newer antiseizure medications are needed,” Dr. Meador added. “Further, additional research is needed on the underlying mechanisms including genetic predispositions, since teratogens act on a susceptible genotype.”
The study was supported by the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
A version of this article first appeared on Medscape.com.
Further evidence supporting the safety of two antiseizure medications in pregnancy has come from a new study. Most of the women with epilepsy in the study took either lamotrigine or levetiracetam, or a combination of the two, during their pregnancy.
However, a secondary analysis suggested a possible signal of exposure-dependent effects on child outcomes – worse outcomes with higher exposure levels – with levetiracetam.
The results were presented at the American Academy of Neurology’s 2021 annual meeting.
Additional reassurance
“Our new study adds confidence to the use of lamotrigine and levetiracetam during pregnancy, adding larger numbers with a new cohort. In addition, it provides some preliminary data on some of the other new antiseizure medications, and it is the first study to address the effects of clearance in pregnancy to better assess exposure,” said lead investigator, Kimford J. Meador, MD. “Overall, I am reassured by this data, but there is still a lot that is unknown,” he added.
“Our main results show no difference in verbal index or general conceptual ability scores in children born to women with epilepsy compared to children born to healthy women. This is a big positive message,” Dr. Meador said.
In terms of secondary analysis focusing on exposure levels (dose and blood levels of antiseizure medications), there was no overall signal of harm when looking at the whole group, but when the researchers analyzed the data on individual drugs, they found a “slight signal” toward reduced verbal index scores with increasing exposure levels with levetiracetam. No differences were seen on general conceptual ability.
“In the secondary analysis, there was a marginal signal for exposure levels with levetiracetam, with increased blood levels of the drug associated with reduced verbal index scores,” reported Dr. Meador, professor of neurology and neurological sciences at Stanford (Calif.) University. “We saw some signal in the children when they were 2 years old, and this was still there but not as striking at 3 years old.”
He said these secondary results should be interpreted with extreme caution. “We don’t want to overemphasize these secondary findings, as the primary outcome showed no difference, and there was no effect on exposure levels when looking at all the drugs together. I don’t want to oversimplify this, as I am still not sure whether this is a real association or not,” Dr. Meador commented.
He explained that conducting neurobehavioral tests on 2- and 3-year-olds was very difficult. “It is more of an art form than science, and as the children get older these signals often dissipate. We will know more by the time they are 6, when these tests become easier to conduct,” he said. He also noted that the results would need to be replicated in a different cohort.
“I don’t think these results would change how we manage women during pregnancy in terms of using levetiracetam. It is still a safe drug during pregnancy,” Dr. Meador said.
He pointed out that data on safety in pregnancy is only available for very few antiseizure drugs. “There are over 30 antiseizure medications, but we have adequate data in pregnancy on only a handful. We have data suggesting lamotrigine, levetiracetam, and carbamazepine appear to be relatively safe, and evidence showing phenobarbital and valproate are not safe.”
Antiseizure medications as a class are among the most commonly prescribed teratogenic drugs given to women of childbearing age, Dr. Meador noted. They are used not only for epilepsy but also for many other psychiatric and pain indications, so these results are applicable to quite a broad population, he added.
He pointed out that previous studies did not assess exposure using blood levels, which is important, as clearance of drug increases during pregnancy but varies across antiseizure medications and across individuals on the same drug. “Thus, it is unclear if these changes could obscure exposure-dependent effects. Our present studies assessed blood levels to better measure fetal exposure.”
Advice for pregnant patients with epilepsy
Dr. Meador explained that risk for adverse effects with antiseizure medication always needs to be balanced with risk for seizures if the medication was not used.
“In women planning a pregnancy, we recommend that they plan ahead with their physician to try and use the safest antiseizure medication and gain good control beforehand and then maintain the same blood levels of whichever drug is being used during pregnancy,” Dr. Meador said. “At present, lamotrigine and levetiracetam are the two safest drugs to use in pregnancy. They both look generally very safe compared with some other epilepsy drugs – such as valproate, which poses a serious risk to cognitive and behavioral development.”
He also advised that women should be taking folic acid regularly, as this has been shown to be related to improved cognitive and behavioral outcomes. “Since half of pregnancies are not planned, it is important to take these actions before pregnancy,” he added.
The current study involved 289 women with epilepsy and 89 women without epilepsy, all of whom enrolled in the study during pregnancy. Use of antiseizure medications was recorded. Of the women with epilepsy, 74% were on monotherapy, with 43% on lamotrigine and 37% on levetiracetam. There were 4% who took no drug and 22% took more than one drug. Of those who took more than one drug, close to half took a combination of lamotrigine and levetiracetam. Levels of medications in the blood of the women with epilepsy were measured in the third trimester.
Assessment of neurobehavioral development
For the current analysis, the children were evaluated at age 3 with a series of cognitive and developmental tests that measured vocabulary, listening comprehension, number recall, and pattern recognition, and results were adjusted for mother’s IQ, education level, age at enrollment, postbirth average BAI (Beck Anxiety Inventory score), and child’s ethnicity, sex, and breastfeeding status.
The primary outcome showed that verbal Index scores at age 3 did not differ for children of women with epilepsy versus those for children of women without epilepsy (LS mean 102.7 vs. 102.1).
Antiseizure medication exposure as evident by the maximum third trimester blood levels was not related to verbal index scores (n = 265; adjusted parameter estimate, -1.9; 95% confidence interval, -6.8 to 3.1).
General conceptual ability scores also did not differ between the two groups: 105.1 for children of women with epilepsy versus 103.5 for children of healthy women.
In terms of exposure levels, the third trimester maximum observed ratio of antiseizure medication blood levels was not significantly associated with adjusted general conceptual ability scores for children of women with epilepsy; neither were monotherapies or polytherapies evaluated separately, Dr. Meador reported.
However, when the verbal index scores for the main antiepileptic drug groups were analyzed separately, exposure level to levetiracetam was the only one that was significant, with a P value of .028. But Dr. Meador again stressed that this finding should be interpreted with caution given that it is a secondary exploratory analysis without control for multiple comparisons.
The researchers plan to assess these children at older ages where evaluations are more sensitive to ultimate outcomes.
“Information on use in pregnancy for most antiseizure medications is still unknown, so further studies to assess risks for the newer antiseizure medications are needed,” Dr. Meador added. “Further, additional research is needed on the underlying mechanisms including genetic predispositions, since teratogens act on a susceptible genotype.”
The study was supported by the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
A version of this article first appeared on Medscape.com.
Further evidence supporting the safety of two antiseizure medications in pregnancy has come from a new study. Most of the women with epilepsy in the study took either lamotrigine or levetiracetam, or a combination of the two, during their pregnancy.
However, a secondary analysis suggested a possible signal of exposure-dependent effects on child outcomes – worse outcomes with higher exposure levels – with levetiracetam.
The results were presented at the American Academy of Neurology’s 2021 annual meeting.
Additional reassurance
“Our new study adds confidence to the use of lamotrigine and levetiracetam during pregnancy, adding larger numbers with a new cohort. In addition, it provides some preliminary data on some of the other new antiseizure medications, and it is the first study to address the effects of clearance in pregnancy to better assess exposure,” said lead investigator, Kimford J. Meador, MD. “Overall, I am reassured by this data, but there is still a lot that is unknown,” he added.
“Our main results show no difference in verbal index or general conceptual ability scores in children born to women with epilepsy compared to children born to healthy women. This is a big positive message,” Dr. Meador said.
In terms of secondary analysis focusing on exposure levels (dose and blood levels of antiseizure medications), there was no overall signal of harm when looking at the whole group, but when the researchers analyzed the data on individual drugs, they found a “slight signal” toward reduced verbal index scores with increasing exposure levels with levetiracetam. No differences were seen on general conceptual ability.
“In the secondary analysis, there was a marginal signal for exposure levels with levetiracetam, with increased blood levels of the drug associated with reduced verbal index scores,” reported Dr. Meador, professor of neurology and neurological sciences at Stanford (Calif.) University. “We saw some signal in the children when they were 2 years old, and this was still there but not as striking at 3 years old.”
He said these secondary results should be interpreted with extreme caution. “We don’t want to overemphasize these secondary findings, as the primary outcome showed no difference, and there was no effect on exposure levels when looking at all the drugs together. I don’t want to oversimplify this, as I am still not sure whether this is a real association or not,” Dr. Meador commented.
He explained that conducting neurobehavioral tests on 2- and 3-year-olds was very difficult. “It is more of an art form than science, and as the children get older these signals often dissipate. We will know more by the time they are 6, when these tests become easier to conduct,” he said. He also noted that the results would need to be replicated in a different cohort.
“I don’t think these results would change how we manage women during pregnancy in terms of using levetiracetam. It is still a safe drug during pregnancy,” Dr. Meador said.
He pointed out that data on safety in pregnancy is only available for very few antiseizure drugs. “There are over 30 antiseizure medications, but we have adequate data in pregnancy on only a handful. We have data suggesting lamotrigine, levetiracetam, and carbamazepine appear to be relatively safe, and evidence showing phenobarbital and valproate are not safe.”
Antiseizure medications as a class are among the most commonly prescribed teratogenic drugs given to women of childbearing age, Dr. Meador noted. They are used not only for epilepsy but also for many other psychiatric and pain indications, so these results are applicable to quite a broad population, he added.
He pointed out that previous studies did not assess exposure using blood levels, which is important, as clearance of drug increases during pregnancy but varies across antiseizure medications and across individuals on the same drug. “Thus, it is unclear if these changes could obscure exposure-dependent effects. Our present studies assessed blood levels to better measure fetal exposure.”
Advice for pregnant patients with epilepsy
Dr. Meador explained that risk for adverse effects with antiseizure medication always needs to be balanced with risk for seizures if the medication was not used.
“In women planning a pregnancy, we recommend that they plan ahead with their physician to try and use the safest antiseizure medication and gain good control beforehand and then maintain the same blood levels of whichever drug is being used during pregnancy,” Dr. Meador said. “At present, lamotrigine and levetiracetam are the two safest drugs to use in pregnancy. They both look generally very safe compared with some other epilepsy drugs – such as valproate, which poses a serious risk to cognitive and behavioral development.”
He also advised that women should be taking folic acid regularly, as this has been shown to be related to improved cognitive and behavioral outcomes. “Since half of pregnancies are not planned, it is important to take these actions before pregnancy,” he added.
The current study involved 289 women with epilepsy and 89 women without epilepsy, all of whom enrolled in the study during pregnancy. Use of antiseizure medications was recorded. Of the women with epilepsy, 74% were on monotherapy, with 43% on lamotrigine and 37% on levetiracetam. There were 4% who took no drug and 22% took more than one drug. Of those who took more than one drug, close to half took a combination of lamotrigine and levetiracetam. Levels of medications in the blood of the women with epilepsy were measured in the third trimester.
Assessment of neurobehavioral development
For the current analysis, the children were evaluated at age 3 with a series of cognitive and developmental tests that measured vocabulary, listening comprehension, number recall, and pattern recognition, and results were adjusted for mother’s IQ, education level, age at enrollment, postbirth average BAI (Beck Anxiety Inventory score), and child’s ethnicity, sex, and breastfeeding status.
The primary outcome showed that verbal Index scores at age 3 did not differ for children of women with epilepsy versus those for children of women without epilepsy (LS mean 102.7 vs. 102.1).
Antiseizure medication exposure as evident by the maximum third trimester blood levels was not related to verbal index scores (n = 265; adjusted parameter estimate, -1.9; 95% confidence interval, -6.8 to 3.1).
General conceptual ability scores also did not differ between the two groups: 105.1 for children of women with epilepsy versus 103.5 for children of healthy women.
In terms of exposure levels, the third trimester maximum observed ratio of antiseizure medication blood levels was not significantly associated with adjusted general conceptual ability scores for children of women with epilepsy; neither were monotherapies or polytherapies evaluated separately, Dr. Meador reported.
However, when the verbal index scores for the main antiepileptic drug groups were analyzed separately, exposure level to levetiracetam was the only one that was significant, with a P value of .028. But Dr. Meador again stressed that this finding should be interpreted with caution given that it is a secondary exploratory analysis without control for multiple comparisons.
The researchers plan to assess these children at older ages where evaluations are more sensitive to ultimate outcomes.
“Information on use in pregnancy for most antiseizure medications is still unknown, so further studies to assess risks for the newer antiseizure medications are needed,” Dr. Meador added. “Further, additional research is needed on the underlying mechanisms including genetic predispositions, since teratogens act on a susceptible genotype.”
The study was supported by the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
A version of this article first appeared on Medscape.com.
From AAN 2021
COVID-19 linked to novel epileptic seizures
, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.
In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.
“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.
Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”
“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.
Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
Largest sample to date
“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.
Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.
However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.
For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.
For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).
The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
Significant adverse outcomes
Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).
In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).
In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).
Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).
Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.
Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”
He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”
Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.
The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.
In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.
“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.
Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”
“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.
Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
Largest sample to date
“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.
Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.
However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.
For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.
For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).
The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
Significant adverse outcomes
Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).
In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).
In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).
Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).
Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.
Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”
He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”
Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.
The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.
In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.
“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.
Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”
“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.
Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
Largest sample to date
“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.
Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.
However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.
For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.
For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).
The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
Significant adverse outcomes
Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).
In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).
In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).
Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).
Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.
Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”
He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”
Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.
The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAN 2021
Prenatal dietary folate not enough to offset AEDs’ effect on kids’ cognition
New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).
Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.
“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.
“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.
The findings were published online Feb. 23 in Epilepsy and Behavior.
Cognitive boost
“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.
Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.
To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.
Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.
In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).
These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
Optimal dose unclear
The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.
Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.
The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.
“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.
For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
Proves a point?
Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.
“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.
He cautioned that the current analysis included only four medications, three of which are not used very often anymore.
“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.
The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).
Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.
“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.
“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.
The findings were published online Feb. 23 in Epilepsy and Behavior.
Cognitive boost
“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.
Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.
To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.
Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.
In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).
These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
Optimal dose unclear
The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.
Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.
The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.
“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.
For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
Proves a point?
Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.
“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.
He cautioned that the current analysis included only four medications, three of which are not used very often anymore.
“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.
The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).
Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.
“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.
“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.
The findings were published online Feb. 23 in Epilepsy and Behavior.
Cognitive boost
“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.
Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.
To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.
Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.
In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).
These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
Optimal dose unclear
The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.
Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.
The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.
“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.
For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
Proves a point?
Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.
“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.
He cautioned that the current analysis included only four medications, three of which are not used very often anymore.
“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.
The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Neurologic drug prices jump 50% in five years
, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).
“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.
“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.
The study findings were published online March 10 in the journal Neurology.
$26 billion in payments
Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.
To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.
In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.
To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.
The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.
Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.
From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.
However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
Treatment barrier
Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.
When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).
Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”
Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.
“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
‘Unfettered’ price-setting
Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.
Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.
Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.
He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.
Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.
The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.
A version of this article first appeared on Medscape.com.
, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).
“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.
“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.
The study findings were published online March 10 in the journal Neurology.
$26 billion in payments
Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.
To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.
In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.
To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.
The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.
Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.
From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.
However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
Treatment barrier
Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.
When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).
Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”
Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.
“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
‘Unfettered’ price-setting
Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.
Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.
Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.
He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.
Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.
The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.
A version of this article first appeared on Medscape.com.
, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).
“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.
“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.
The study findings were published online March 10 in the journal Neurology.
$26 billion in payments
Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.
To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.
In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.
To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.
The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.
Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.
From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.
However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
Treatment barrier
Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.
When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).
Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”
Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.
“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
‘Unfettered’ price-setting
Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.
Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.
Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.
He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.
Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.
The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Neurologic disorders ubiquitous and rising in the U.S.
, according to new findings derived from the 2017 Global Burden of Disease study.
The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
Tracking the burden of neurologic diseases
Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.
The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.
The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.
Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
Regional variations
The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”
Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.
Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”
The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
Time to adjust the stroke belt?
Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia.
“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”
Dr. Boehme disclosed no financial conflicts of interest.
, according to new findings derived from the 2017 Global Burden of Disease study.
The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
Tracking the burden of neurologic diseases
Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.
The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.
The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.
Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
Regional variations
The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”
Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.
Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”
The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
Time to adjust the stroke belt?
Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia.
“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”
Dr. Boehme disclosed no financial conflicts of interest.
, according to new findings derived from the 2017 Global Burden of Disease study.
The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
Tracking the burden of neurologic diseases
Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.
The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.
The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.
Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
Regional variations
The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”
Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.
Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”
The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
Time to adjust the stroke belt?
Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia.
“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”
Dr. Boehme disclosed no financial conflicts of interest.
FROM JAMA NEUROLOGY
EEG data may help aid diagnosis, treatment of focal epilepsy
, new research suggests. Findings from a large longitudinal study show that seizure onset in patients with focal epilepsy follows circadian, multiday, and annual cycles.
“Although daily and multiday rhythms have previously been identified, the extent to which these nonrandom rhythms exist in a larger cohort has been unclear,” said study investigator Joline Marie Fan, MD, a clinical fellow at the University of California, San Francisco. “This means that a patient with epilepsy may have a unique combination of seizure rhythms that can inform the days and timing of his or her highest seizure risk,” she added.
The study was published online Feb. 8 in JAMA Neurology.
Distinct chronotypes
Clinicians and patients alike have long observed cyclical patterns in the onset of epileptic seizures. However, such patterns have rarely been measured in a quantitative way.
Previous studies have examined seizure cycles using inpatient seizure monitoring and patients’ seizure diaries, but the duration of these recordings and their accuracy have been limited. Within the past decade, the advent of cEEG has allowed researchers to observe the cyclical pattern of interictal epileptiform activity, but the numbers of patients involved in such studies have been limited.
To investigate seizure chronotypes in greater detail, the researchers examined retrospective data for 222 adults with medically refractory focal epilepsy who took part in clinical trials of the NeuroPace responsive neurostimulation (RNS) system.
After implantation in the brain, this system monitors the seizure focus or foci continuously and delivers stimulation to stop seizures. Participants also kept seizure diaries and classified their seizures as simple motor, simple other, complex partial, and generalized tonic-clonic.
Dr. Fan’s group examined three subpopulations of patients to investigate three durations of seizure cycles. They examined self-reported disabling seizures, electrographic seizures, and interictal epileptiform activity. Because patients did not record the time of their disabling seizures, the investigators examined them only in multidien and circannual cycles.
To examine circannual seizure cycles, the investigators included 194 patients who kept continuous seizure diaries for 2 or more years and who reported 24 or more days in which disabling seizures occurred.
To examine multidien seizure cycles, they included 186 participants who reported 24 or more days with disabling seizures over a period of 6 or more months during which the RNS system collected cEEG data. They included 85 patients who had 48 hours or more in which electrographic seizure counts were above zero during 6 or more months of cEEG data collection to examine circadian seizure cycles.
Phase-locking value (PLV) was used to determine the strength of a cycle (i.e., the degree of consistency with which seizures occur during certain phases of a cycle). A PLV of 0 represents a uniform distribution of events during various phases of a cycle; a PLV of 1 indicates that all events occur exactly at the same phase of a cycle.
The population’s median age was 35 years, and the sample included approximately equal numbers of men and women. Patients’ focal epilepsies included mesiotemporal (57.2%), frontal (14.0%), neocortical-temporal (9.9%), parietal (4.1%), occipital (1.4%), and multifocal (13.5%). The data included 1,118 patient-years of cEEG, 754,108 electrographic seizures, and 313,995 self-reported seizures.
The prevalence of statistically significant circannual seizure cycles in this population was 12%. The prevalence of multidien seizure cycles was 60%, and the prevalence of circadian seizure cycles was 89%. Multidien cycles (mean PLV, 0.34) and circadian cycles (mean PLV, 0.34) were stronger than were circannual cycles (mean PLV, 0.17).
Among patients with circannual seizure cycles, there was a weak to moderate tendency for seizures to occur during one of the four seasons. There was no overall trend toward seizure onset in one season among this group.
Among patients with multidien seizure cycles, investigators identified five patterns of interictal epileptiform activity fluctuations. One pattern had irregular periodicity, and the others reached peak periodicity at 7, 15, 20, and 30 days. For some patients, one or more periodicities occurred. For most patients, electrographic or self-reported seizures tended to occur on the rising phase of the interictal epileptiform activity cycle. Interictal epileptiform activity increased on days around seizures.
Results showed there were five main seizure peak times among patients with circadian seizure cycles: midnight, 3:00 a.m., 9:00 a.m., 2:00 p.m., and 6:00 p.m. These findings corroborate the observations of previous investigations, the researchers noted. Hourly interictal epileptiform activity peaked during the night, regardless of peak seizure time.
“Although the neurostimulation device offers us a unique opportunity to investigate electrographic seizure activity quantitatively, the generalizability of our study is limited to the patient cohort that we studied,” said Dr. Fan. “The study findings are limited to patients with neurostimulation devices used for intractable focal epilepsies.”
The results support patients’ impressions that their seizures occur in a cyclical pattern.
“Ultimately, these findings will be helpful for developing models to aid with seizure forecasting and prediction in order to help reduce the uncertainty of seizure timing for patients with epilepsy,” said Dr. Fan.
“Other implications include optimizing the timing for patients to be admitted into the hospital for seizure characterization based on their seizure chronotype, or possibly tailoring a medication regimen in accordance with a patient’s seizure cycles,” she added.
Need for more research
Commenting on the findings, Tobias Loddenkemper, MD, professor of neurology at Harvard Medical School, Boston, noted that the study is “one of the largest longitudinal seizure pattern analyses, based on the gold standard of intracranially recorded epileptic seizures.”
The research, he added, extends neurologists’ understanding of seizure patterns over time, expands knowledge about seizure chronotypes, and emphasizes a relationship between interictal epileptiform activity and seizures.
The strengths of the study include the recording of seizures with intracranial EEG, its large number of participants, and the long duration of recordings, Dr. Loddenkemper said.
However, he said, it is important to note that self-reports are not always reliable. The results may also reflect the influence of potential confounders of seizure patterns, such as seizure triggers, treatment, stimulation, or sleep-wake, circadian, or hormonal cycles, he added.
“In the short term, validation studies, as well as confirmatory studies with less invasive sensors, may be needed,” said Dr. Loddenkemper.
“This could potentially include a trial that confirms findings prospectively, utilizing results from video EEG monitoring admissions. In the long term, seizure detection and prediction, as well as interventional chronotherapeutic trials, may be enabled, predicting seizures in individual patients and treating at times of greatest seizure susceptibility.”
The study was supported by grants to some of the authors from the Wyss Center for Bio and Neuroengineering, the Ernest Gallo Foundation, the Swiss National Science Foundation, and the Velux Stiftung. Dr. Fan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Findings from a large longitudinal study show that seizure onset in patients with focal epilepsy follows circadian, multiday, and annual cycles.
“Although daily and multiday rhythms have previously been identified, the extent to which these nonrandom rhythms exist in a larger cohort has been unclear,” said study investigator Joline Marie Fan, MD, a clinical fellow at the University of California, San Francisco. “This means that a patient with epilepsy may have a unique combination of seizure rhythms that can inform the days and timing of his or her highest seizure risk,” she added.
The study was published online Feb. 8 in JAMA Neurology.
Distinct chronotypes
Clinicians and patients alike have long observed cyclical patterns in the onset of epileptic seizures. However, such patterns have rarely been measured in a quantitative way.
Previous studies have examined seizure cycles using inpatient seizure monitoring and patients’ seizure diaries, but the duration of these recordings and their accuracy have been limited. Within the past decade, the advent of cEEG has allowed researchers to observe the cyclical pattern of interictal epileptiform activity, but the numbers of patients involved in such studies have been limited.
To investigate seizure chronotypes in greater detail, the researchers examined retrospective data for 222 adults with medically refractory focal epilepsy who took part in clinical trials of the NeuroPace responsive neurostimulation (RNS) system.
After implantation in the brain, this system monitors the seizure focus or foci continuously and delivers stimulation to stop seizures. Participants also kept seizure diaries and classified their seizures as simple motor, simple other, complex partial, and generalized tonic-clonic.
Dr. Fan’s group examined three subpopulations of patients to investigate three durations of seizure cycles. They examined self-reported disabling seizures, electrographic seizures, and interictal epileptiform activity. Because patients did not record the time of their disabling seizures, the investigators examined them only in multidien and circannual cycles.
To examine circannual seizure cycles, the investigators included 194 patients who kept continuous seizure diaries for 2 or more years and who reported 24 or more days in which disabling seizures occurred.
To examine multidien seizure cycles, they included 186 participants who reported 24 or more days with disabling seizures over a period of 6 or more months during which the RNS system collected cEEG data. They included 85 patients who had 48 hours or more in which electrographic seizure counts were above zero during 6 or more months of cEEG data collection to examine circadian seizure cycles.
Phase-locking value (PLV) was used to determine the strength of a cycle (i.e., the degree of consistency with which seizures occur during certain phases of a cycle). A PLV of 0 represents a uniform distribution of events during various phases of a cycle; a PLV of 1 indicates that all events occur exactly at the same phase of a cycle.
The population’s median age was 35 years, and the sample included approximately equal numbers of men and women. Patients’ focal epilepsies included mesiotemporal (57.2%), frontal (14.0%), neocortical-temporal (9.9%), parietal (4.1%), occipital (1.4%), and multifocal (13.5%). The data included 1,118 patient-years of cEEG, 754,108 electrographic seizures, and 313,995 self-reported seizures.
The prevalence of statistically significant circannual seizure cycles in this population was 12%. The prevalence of multidien seizure cycles was 60%, and the prevalence of circadian seizure cycles was 89%. Multidien cycles (mean PLV, 0.34) and circadian cycles (mean PLV, 0.34) were stronger than were circannual cycles (mean PLV, 0.17).
Among patients with circannual seizure cycles, there was a weak to moderate tendency for seizures to occur during one of the four seasons. There was no overall trend toward seizure onset in one season among this group.
Among patients with multidien seizure cycles, investigators identified five patterns of interictal epileptiform activity fluctuations. One pattern had irregular periodicity, and the others reached peak periodicity at 7, 15, 20, and 30 days. For some patients, one or more periodicities occurred. For most patients, electrographic or self-reported seizures tended to occur on the rising phase of the interictal epileptiform activity cycle. Interictal epileptiform activity increased on days around seizures.
Results showed there were five main seizure peak times among patients with circadian seizure cycles: midnight, 3:00 a.m., 9:00 a.m., 2:00 p.m., and 6:00 p.m. These findings corroborate the observations of previous investigations, the researchers noted. Hourly interictal epileptiform activity peaked during the night, regardless of peak seizure time.
“Although the neurostimulation device offers us a unique opportunity to investigate electrographic seizure activity quantitatively, the generalizability of our study is limited to the patient cohort that we studied,” said Dr. Fan. “The study findings are limited to patients with neurostimulation devices used for intractable focal epilepsies.”
The results support patients’ impressions that their seizures occur in a cyclical pattern.
“Ultimately, these findings will be helpful for developing models to aid with seizure forecasting and prediction in order to help reduce the uncertainty of seizure timing for patients with epilepsy,” said Dr. Fan.
“Other implications include optimizing the timing for patients to be admitted into the hospital for seizure characterization based on their seizure chronotype, or possibly tailoring a medication regimen in accordance with a patient’s seizure cycles,” she added.
Need for more research
Commenting on the findings, Tobias Loddenkemper, MD, professor of neurology at Harvard Medical School, Boston, noted that the study is “one of the largest longitudinal seizure pattern analyses, based on the gold standard of intracranially recorded epileptic seizures.”
The research, he added, extends neurologists’ understanding of seizure patterns over time, expands knowledge about seizure chronotypes, and emphasizes a relationship between interictal epileptiform activity and seizures.
The strengths of the study include the recording of seizures with intracranial EEG, its large number of participants, and the long duration of recordings, Dr. Loddenkemper said.
However, he said, it is important to note that self-reports are not always reliable. The results may also reflect the influence of potential confounders of seizure patterns, such as seizure triggers, treatment, stimulation, or sleep-wake, circadian, or hormonal cycles, he added.
“In the short term, validation studies, as well as confirmatory studies with less invasive sensors, may be needed,” said Dr. Loddenkemper.
“This could potentially include a trial that confirms findings prospectively, utilizing results from video EEG monitoring admissions. In the long term, seizure detection and prediction, as well as interventional chronotherapeutic trials, may be enabled, predicting seizures in individual patients and treating at times of greatest seizure susceptibility.”
The study was supported by grants to some of the authors from the Wyss Center for Bio and Neuroengineering, the Ernest Gallo Foundation, the Swiss National Science Foundation, and the Velux Stiftung. Dr. Fan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Findings from a large longitudinal study show that seizure onset in patients with focal epilepsy follows circadian, multiday, and annual cycles.
“Although daily and multiday rhythms have previously been identified, the extent to which these nonrandom rhythms exist in a larger cohort has been unclear,” said study investigator Joline Marie Fan, MD, a clinical fellow at the University of California, San Francisco. “This means that a patient with epilepsy may have a unique combination of seizure rhythms that can inform the days and timing of his or her highest seizure risk,” she added.
The study was published online Feb. 8 in JAMA Neurology.
Distinct chronotypes
Clinicians and patients alike have long observed cyclical patterns in the onset of epileptic seizures. However, such patterns have rarely been measured in a quantitative way.
Previous studies have examined seizure cycles using inpatient seizure monitoring and patients’ seizure diaries, but the duration of these recordings and their accuracy have been limited. Within the past decade, the advent of cEEG has allowed researchers to observe the cyclical pattern of interictal epileptiform activity, but the numbers of patients involved in such studies have been limited.
To investigate seizure chronotypes in greater detail, the researchers examined retrospective data for 222 adults with medically refractory focal epilepsy who took part in clinical trials of the NeuroPace responsive neurostimulation (RNS) system.
After implantation in the brain, this system monitors the seizure focus or foci continuously and delivers stimulation to stop seizures. Participants also kept seizure diaries and classified their seizures as simple motor, simple other, complex partial, and generalized tonic-clonic.
Dr. Fan’s group examined three subpopulations of patients to investigate three durations of seizure cycles. They examined self-reported disabling seizures, electrographic seizures, and interictal epileptiform activity. Because patients did not record the time of their disabling seizures, the investigators examined them only in multidien and circannual cycles.
To examine circannual seizure cycles, the investigators included 194 patients who kept continuous seizure diaries for 2 or more years and who reported 24 or more days in which disabling seizures occurred.
To examine multidien seizure cycles, they included 186 participants who reported 24 or more days with disabling seizures over a period of 6 or more months during which the RNS system collected cEEG data. They included 85 patients who had 48 hours or more in which electrographic seizure counts were above zero during 6 or more months of cEEG data collection to examine circadian seizure cycles.
Phase-locking value (PLV) was used to determine the strength of a cycle (i.e., the degree of consistency with which seizures occur during certain phases of a cycle). A PLV of 0 represents a uniform distribution of events during various phases of a cycle; a PLV of 1 indicates that all events occur exactly at the same phase of a cycle.
The population’s median age was 35 years, and the sample included approximately equal numbers of men and women. Patients’ focal epilepsies included mesiotemporal (57.2%), frontal (14.0%), neocortical-temporal (9.9%), parietal (4.1%), occipital (1.4%), and multifocal (13.5%). The data included 1,118 patient-years of cEEG, 754,108 electrographic seizures, and 313,995 self-reported seizures.
The prevalence of statistically significant circannual seizure cycles in this population was 12%. The prevalence of multidien seizure cycles was 60%, and the prevalence of circadian seizure cycles was 89%. Multidien cycles (mean PLV, 0.34) and circadian cycles (mean PLV, 0.34) were stronger than were circannual cycles (mean PLV, 0.17).
Among patients with circannual seizure cycles, there was a weak to moderate tendency for seizures to occur during one of the four seasons. There was no overall trend toward seizure onset in one season among this group.
Among patients with multidien seizure cycles, investigators identified five patterns of interictal epileptiform activity fluctuations. One pattern had irregular periodicity, and the others reached peak periodicity at 7, 15, 20, and 30 days. For some patients, one or more periodicities occurred. For most patients, electrographic or self-reported seizures tended to occur on the rising phase of the interictal epileptiform activity cycle. Interictal epileptiform activity increased on days around seizures.
Results showed there were five main seizure peak times among patients with circadian seizure cycles: midnight, 3:00 a.m., 9:00 a.m., 2:00 p.m., and 6:00 p.m. These findings corroborate the observations of previous investigations, the researchers noted. Hourly interictal epileptiform activity peaked during the night, regardless of peak seizure time.
“Although the neurostimulation device offers us a unique opportunity to investigate electrographic seizure activity quantitatively, the generalizability of our study is limited to the patient cohort that we studied,” said Dr. Fan. “The study findings are limited to patients with neurostimulation devices used for intractable focal epilepsies.”
The results support patients’ impressions that their seizures occur in a cyclical pattern.
“Ultimately, these findings will be helpful for developing models to aid with seizure forecasting and prediction in order to help reduce the uncertainty of seizure timing for patients with epilepsy,” said Dr. Fan.
“Other implications include optimizing the timing for patients to be admitted into the hospital for seizure characterization based on their seizure chronotype, or possibly tailoring a medication regimen in accordance with a patient’s seizure cycles,” she added.
Need for more research
Commenting on the findings, Tobias Loddenkemper, MD, professor of neurology at Harvard Medical School, Boston, noted that the study is “one of the largest longitudinal seizure pattern analyses, based on the gold standard of intracranially recorded epileptic seizures.”
The research, he added, extends neurologists’ understanding of seizure patterns over time, expands knowledge about seizure chronotypes, and emphasizes a relationship between interictal epileptiform activity and seizures.
The strengths of the study include the recording of seizures with intracranial EEG, its large number of participants, and the long duration of recordings, Dr. Loddenkemper said.
However, he said, it is important to note that self-reports are not always reliable. The results may also reflect the influence of potential confounders of seizure patterns, such as seizure triggers, treatment, stimulation, or sleep-wake, circadian, or hormonal cycles, he added.
“In the short term, validation studies, as well as confirmatory studies with less invasive sensors, may be needed,” said Dr. Loddenkemper.
“This could potentially include a trial that confirms findings prospectively, utilizing results from video EEG monitoring admissions. In the long term, seizure detection and prediction, as well as interventional chronotherapeutic trials, may be enabled, predicting seizures in individual patients and treating at times of greatest seizure susceptibility.”
The study was supported by grants to some of the authors from the Wyss Center for Bio and Neuroengineering, the Ernest Gallo Foundation, the Swiss National Science Foundation, and the Velux Stiftung. Dr. Fan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Physicians react: Doctors worry about patients reading their clinical notes
Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.
As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.
The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
Potentially more legal woes for physicians?
A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.
“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.
She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.
Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?
As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”
The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.
“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”
One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”
Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.
One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
Will Open Notes erode patient communication?
One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.
“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
Some physicians envision positive developments
Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.
A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.
“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.
“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”
One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.
Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”
Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”
“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”
“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”
A version of this article first appeared on Medscape.com.
Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.
As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.
The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
Potentially more legal woes for physicians?
A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.
“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.
She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.
Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?
As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”
The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.
“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”
One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”
Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.
One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
Will Open Notes erode patient communication?
One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.
“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
Some physicians envision positive developments
Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.
A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.
“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.
“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”
One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.
Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”
Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”
“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”
“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”
A version of this article first appeared on Medscape.com.
Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.
As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.
The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
Potentially more legal woes for physicians?
A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.
“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.
She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.
Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?
As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”
The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.
“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”
One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”
Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.
One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
Will Open Notes erode patient communication?
One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.
“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
Some physicians envision positive developments
Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.
A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.
“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.
“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”
One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.
Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”
Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”
“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”
“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”
A version of this article first appeared on Medscape.com.
Encouraging results for new epilepsy drug
Post hoc analyses from an open-label study showed that seizure frequency was significantly reduced and the seizure-freedom rate was significantly improved among 240 adult participants who received cenobamate. The patients’ use of concomitant antiseizure medications was also reduced, with no effect on efficacy.
These results are “fascinating” and “very, very exciting,” said lead author William E. Rosenfeld, MD, director, Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Mo. Although responder rates were impressive, at 50% or greater and 75% or greater, “what patients really want is to have seizure freedom, or at least a 90% reduction in seizures,” Dr. Rosenfeld said.
The findings were presented at the annual meeting of the American Epilepsy Society, held online this year.
Adverse events
Cenobamate reduces seizures by inhibiting sodium current or affecting the GABAA channel, or potentially through a combination of these two mechanisms, said Dr. Rosenfeld. The drug was approved by the U.S. Food and Drug Administration in November 2019 for the treatment of uncontrolled partial-onset seizures in adults, which represent about 60% of all epileptic seizures. It has been on the market since May 2020.
During the drug’s development, three cases of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred. This condition typically involves a skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities, including a high level of eosinophils. However, an open-label study, published earlier this year in Epilepsia, that assessed safety and pharmacokinetics in 1,347 patients aged 18-70 years who received stable doses of one to three antiseizure medications showed that, with “slow and low titration” of cenobamate, there were no cases of DRESS, Dr. Rosenfeld said.
In that safety study, investigators administered increasing daily doses of cenobamate at 12.5, 25, 50, 100, 150, and 200 mg/day at 2-week intervals. If necessary, the dose could be increased to 400 mg/day via 50-mg/day increments every other week.
The researchers presented post hoc analyses regarding 240 patients from 10 U.S. sites who participated in the safety study. Dr. Rosenfeld noted, “These are all good epilepsy centers, and they all kept seizure records.” Of these participants, 177 continued taking the drug as they had at their last visit for a mean of more than 30 months; for some, it was up to 44 months.
“So we had a 73.8% retention rate over the course of the open label, which is the maintenance phase of the study,” Dr. Rosenfeld said.
Among the entire group of 240 patients, 25.8% had been seizure free for more than 12 months at their last visit. Of the 177 who continued to take cenobamate, 33.9% were seizure free for an average of 23.5 months.
“We have never seen those kinds of numbers in the past,” said Dr. Rosenfeld, adding, “it’s so important for patients to get seizure freedom.” These promising results may be related to the fact that the drug works on more than one mechanism of seizure, he speculated.
For some patients, the drug will “make a big difference” by providing them with the best quality of life and allow them to resume normal activities, Dr. Rosenfeld noted. In addition, the drug was well tolerated. The most common adverse events were dizziness/diplopia and sleepiness/drowsiness.
Concomitant drug reductions
Another post hoc analysis of the 240 patients showed that many patients were able to reduce use of other antiseizure medications. At study outset, about 41% were taking lacosamide, 35.7% were taking levetiracetam, and 27.7% were taking lamotrigine. Among patients who continued to take cenobamate, 22.7% of concomitant baseline antiseizure medications were discontinued. Carbamazepine was discontinued by 31.3%, oxcarbazepine by 26.7%, lacosamide by 23.4%, eslicarbazepine by 23.1%, clobazam by 26.7%, lamotrigine by 14.6%, and levetiracetam by 20.3%.
“We found that the patients who stayed in the study the longest had greater reductions in their concomitant antiepileptic mediation,” said Dr. Rosenfeld. Lowering concomitant medications did not reduce efficacy at a target dose of 200 mg/day.
The investigators hope to test the drug in children and in patients with different seizure types.
Promising, with caveats
Commenting on the research, Jong Woo Lee, MD, PhD, associate professor of neurology, the Edward B. Bromfield Epilepsy Program, Brigham and Women’s Hospital, Boston, said cenobamate “has certainly given new hope” to some of his patients. He noted that a few of these patients had been experiencing daily or nearly daily seizures and had been taking three or more medications for many years.
“The chances of another medication being effective for these patients is very low,” said Dr. Lee, who was not involved with the research. “But several of these patients responded to cenobamate, and some of them achieved complete seizure freedom.”
However, as with all new promising medications, there are some caveats. “The concern is for long-term efficacy for more than 5 years and, of course, unforeseen side effects,” Dr. Lee said.
The studies were funded by SK Life Science. Dr. Rosenfeld has been a consultant for SK Life Science. Dr. Lee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Post hoc analyses from an open-label study showed that seizure frequency was significantly reduced and the seizure-freedom rate was significantly improved among 240 adult participants who received cenobamate. The patients’ use of concomitant antiseizure medications was also reduced, with no effect on efficacy.
These results are “fascinating” and “very, very exciting,” said lead author William E. Rosenfeld, MD, director, Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Mo. Although responder rates were impressive, at 50% or greater and 75% or greater, “what patients really want is to have seizure freedom, or at least a 90% reduction in seizures,” Dr. Rosenfeld said.
The findings were presented at the annual meeting of the American Epilepsy Society, held online this year.
Adverse events
Cenobamate reduces seizures by inhibiting sodium current or affecting the GABAA channel, or potentially through a combination of these two mechanisms, said Dr. Rosenfeld. The drug was approved by the U.S. Food and Drug Administration in November 2019 for the treatment of uncontrolled partial-onset seizures in adults, which represent about 60% of all epileptic seizures. It has been on the market since May 2020.
During the drug’s development, three cases of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred. This condition typically involves a skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities, including a high level of eosinophils. However, an open-label study, published earlier this year in Epilepsia, that assessed safety and pharmacokinetics in 1,347 patients aged 18-70 years who received stable doses of one to three antiseizure medications showed that, with “slow and low titration” of cenobamate, there were no cases of DRESS, Dr. Rosenfeld said.
In that safety study, investigators administered increasing daily doses of cenobamate at 12.5, 25, 50, 100, 150, and 200 mg/day at 2-week intervals. If necessary, the dose could be increased to 400 mg/day via 50-mg/day increments every other week.
The researchers presented post hoc analyses regarding 240 patients from 10 U.S. sites who participated in the safety study. Dr. Rosenfeld noted, “These are all good epilepsy centers, and they all kept seizure records.” Of these participants, 177 continued taking the drug as they had at their last visit for a mean of more than 30 months; for some, it was up to 44 months.
“So we had a 73.8% retention rate over the course of the open label, which is the maintenance phase of the study,” Dr. Rosenfeld said.
Among the entire group of 240 patients, 25.8% had been seizure free for more than 12 months at their last visit. Of the 177 who continued to take cenobamate, 33.9% were seizure free for an average of 23.5 months.
“We have never seen those kinds of numbers in the past,” said Dr. Rosenfeld, adding, “it’s so important for patients to get seizure freedom.” These promising results may be related to the fact that the drug works on more than one mechanism of seizure, he speculated.
For some patients, the drug will “make a big difference” by providing them with the best quality of life and allow them to resume normal activities, Dr. Rosenfeld noted. In addition, the drug was well tolerated. The most common adverse events were dizziness/diplopia and sleepiness/drowsiness.
Concomitant drug reductions
Another post hoc analysis of the 240 patients showed that many patients were able to reduce use of other antiseizure medications. At study outset, about 41% were taking lacosamide, 35.7% were taking levetiracetam, and 27.7% were taking lamotrigine. Among patients who continued to take cenobamate, 22.7% of concomitant baseline antiseizure medications were discontinued. Carbamazepine was discontinued by 31.3%, oxcarbazepine by 26.7%, lacosamide by 23.4%, eslicarbazepine by 23.1%, clobazam by 26.7%, lamotrigine by 14.6%, and levetiracetam by 20.3%.
“We found that the patients who stayed in the study the longest had greater reductions in their concomitant antiepileptic mediation,” said Dr. Rosenfeld. Lowering concomitant medications did not reduce efficacy at a target dose of 200 mg/day.
The investigators hope to test the drug in children and in patients with different seizure types.
Promising, with caveats
Commenting on the research, Jong Woo Lee, MD, PhD, associate professor of neurology, the Edward B. Bromfield Epilepsy Program, Brigham and Women’s Hospital, Boston, said cenobamate “has certainly given new hope” to some of his patients. He noted that a few of these patients had been experiencing daily or nearly daily seizures and had been taking three or more medications for many years.
“The chances of another medication being effective for these patients is very low,” said Dr. Lee, who was not involved with the research. “But several of these patients responded to cenobamate, and some of them achieved complete seizure freedom.”
However, as with all new promising medications, there are some caveats. “The concern is for long-term efficacy for more than 5 years and, of course, unforeseen side effects,” Dr. Lee said.
The studies were funded by SK Life Science. Dr. Rosenfeld has been a consultant for SK Life Science. Dr. Lee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Post hoc analyses from an open-label study showed that seizure frequency was significantly reduced and the seizure-freedom rate was significantly improved among 240 adult participants who received cenobamate. The patients’ use of concomitant antiseizure medications was also reduced, with no effect on efficacy.
These results are “fascinating” and “very, very exciting,” said lead author William E. Rosenfeld, MD, director, Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Mo. Although responder rates were impressive, at 50% or greater and 75% or greater, “what patients really want is to have seizure freedom, or at least a 90% reduction in seizures,” Dr. Rosenfeld said.
The findings were presented at the annual meeting of the American Epilepsy Society, held online this year.
Adverse events
Cenobamate reduces seizures by inhibiting sodium current or affecting the GABAA channel, or potentially through a combination of these two mechanisms, said Dr. Rosenfeld. The drug was approved by the U.S. Food and Drug Administration in November 2019 for the treatment of uncontrolled partial-onset seizures in adults, which represent about 60% of all epileptic seizures. It has been on the market since May 2020.
During the drug’s development, three cases of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred. This condition typically involves a skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities, including a high level of eosinophils. However, an open-label study, published earlier this year in Epilepsia, that assessed safety and pharmacokinetics in 1,347 patients aged 18-70 years who received stable doses of one to three antiseizure medications showed that, with “slow and low titration” of cenobamate, there were no cases of DRESS, Dr. Rosenfeld said.
In that safety study, investigators administered increasing daily doses of cenobamate at 12.5, 25, 50, 100, 150, and 200 mg/day at 2-week intervals. If necessary, the dose could be increased to 400 mg/day via 50-mg/day increments every other week.
The researchers presented post hoc analyses regarding 240 patients from 10 U.S. sites who participated in the safety study. Dr. Rosenfeld noted, “These are all good epilepsy centers, and they all kept seizure records.” Of these participants, 177 continued taking the drug as they had at their last visit for a mean of more than 30 months; for some, it was up to 44 months.
“So we had a 73.8% retention rate over the course of the open label, which is the maintenance phase of the study,” Dr. Rosenfeld said.
Among the entire group of 240 patients, 25.8% had been seizure free for more than 12 months at their last visit. Of the 177 who continued to take cenobamate, 33.9% were seizure free for an average of 23.5 months.
“We have never seen those kinds of numbers in the past,” said Dr. Rosenfeld, adding, “it’s so important for patients to get seizure freedom.” These promising results may be related to the fact that the drug works on more than one mechanism of seizure, he speculated.
For some patients, the drug will “make a big difference” by providing them with the best quality of life and allow them to resume normal activities, Dr. Rosenfeld noted. In addition, the drug was well tolerated. The most common adverse events were dizziness/diplopia and sleepiness/drowsiness.
Concomitant drug reductions
Another post hoc analysis of the 240 patients showed that many patients were able to reduce use of other antiseizure medications. At study outset, about 41% were taking lacosamide, 35.7% were taking levetiracetam, and 27.7% were taking lamotrigine. Among patients who continued to take cenobamate, 22.7% of concomitant baseline antiseizure medications were discontinued. Carbamazepine was discontinued by 31.3%, oxcarbazepine by 26.7%, lacosamide by 23.4%, eslicarbazepine by 23.1%, clobazam by 26.7%, lamotrigine by 14.6%, and levetiracetam by 20.3%.
“We found that the patients who stayed in the study the longest had greater reductions in their concomitant antiepileptic mediation,” said Dr. Rosenfeld. Lowering concomitant medications did not reduce efficacy at a target dose of 200 mg/day.
The investigators hope to test the drug in children and in patients with different seizure types.
Promising, with caveats
Commenting on the research, Jong Woo Lee, MD, PhD, associate professor of neurology, the Edward B. Bromfield Epilepsy Program, Brigham and Women’s Hospital, Boston, said cenobamate “has certainly given new hope” to some of his patients. He noted that a few of these patients had been experiencing daily or nearly daily seizures and had been taking three or more medications for many years.
“The chances of another medication being effective for these patients is very low,” said Dr. Lee, who was not involved with the research. “But several of these patients responded to cenobamate, and some of them achieved complete seizure freedom.”
However, as with all new promising medications, there are some caveats. “The concern is for long-term efficacy for more than 5 years and, of course, unforeseen side effects,” Dr. Lee said.
The studies were funded by SK Life Science. Dr. Rosenfeld has been a consultant for SK Life Science. Dr. Lee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AES 2020
Wearable device clears a first ‘milestone’ in seizure detection
The new findings have the potential to revolutionize the management of patients with epilepsy, according to the researchers. “We have set a first benchmark for automatic detection of a variety of epileptic seizures using wearable sensors and deep-learning algorithms. In other words, we have shown for the first time that it’s possible to do this,” said study investigator Jianbin Tang, MA, data science project lead, IBM Research Australia, Victoria.
The findings were presented at the American Epilepsy Society’s annual meeting, held online this year because of the COVID-19 pandemic.
Accurate monitoring of seizures is important for assessing risk, injury prevention, and treatment response evaluation. Currently, video EEG is the gold standard for seizure detection, but it requires a hospital stay, is often costly, and can be stigmatizing, said Mr. Tang.
An advance in detecting seizure types
Recent advances in non-EEG wearable devices show promise in detecting generalized onset tonic-clonic and focal to bilateral tonic-clonic seizures, but it’s not clear if they have the ability to detect other seizure types. “We hope to fill this gap by expanding wearable seizure detection to additional seizure types,” said Mr. Tang.
Seizure tracking outside the hospital setting largely “relies on manually annotated family and patient reports, which often can be unreliable due to missed seizures and problems recalling seizures,” he said.
The study included 75 children (44% were female; mean age was 11.1 years) admitted to a long-term EEG monitoring unit at a single center for a 24-hour stay. Patients wore the detector on the ankle or wrist. The device continuously collected data on functions such as sweating, heart rate, movement, and temperature.
With part of the dataset, researchers trained deep-learning algorithms to automatically detect seizure segments. They then validated the performance of the detection algorithms on the remainder of the dataset.
The analysis was based on data from 722 epileptic seizures of all types including focal and generalized, motor and nonmotor. Seizures occurred throughout the day and during the night while patients were awake or asleep.
When a seizure is detected, the system triggers a real-time alert and will store the information about the detected seizure in a repository, said Mr. Tang.
The signals were initially stored in the wristband and then securely uploaded to the Cloud. From there, the signal files were downloaded by the investigators for analysis and interpretation. All data were entirely anonymized and de-identified. Researchers used Area Under Curve–Receiver Operating Characteristic (AUC-ROC) to assess performance.
“Our best performing detection models reach an AUC-ROC of 67.59%, which represents a decent performance level,” said Mr. Tang. “There certainly is room for performance improvement and we are already working on this,” he added.
The device performed “better than chance,” which is a “standard technical term” in the field of machine learning and is “the first hurdle any machine-learning model needs to take to be considered useful.” The investigators noted that such automatic seizure detection “is feasible across a broad spectrum of epileptic seizure types,” said Mr. Tang. “This is a first and has not been shown before.”
The study suggests that the noninvasive wearable device could be used at home, at school, and in other everyday settings outside the clinic. “This could one day provide patients, caregivers, and clinicians with reliable seizure reports,” said Mr. Tang.
He said he believes the device might be especially useful in detecting frequent or subtle seizures, which are easy to miss. Patients requiring medication evaluation and rescue medication and those at risk of status epilepticus may be good candidates.
The researchers don’t expect wearable technology to totally replace EEG but see it as “a useful complementary tool to track seizures continuously at times or in settings where EEG monitoring is not available,” said Mr. Tang.
‘Important milestone’
Commenting on the research, Benjamin H. Brinkmann, PhD, associate professor of neurology at the Mayo Clinic in Rochester, Minn., said the investigators “have done very good work applying state of the art machine learning techniques” to the “important problem” of accurately detecting seizures.
Dr. Brinkmann is part of the Epilepsy Foundation–sponsored “My Seizure Gauge” project that’s evaluating various wearable devices, including the Empatica E4 wristband and the Fitbit Charge 3, to determine what measurements are needed for reliable seizure forecasting.
“Previously, no one knew whether seizure prediction was possible with these devices, and the fact that this group was able to achieve ‘better-than-chance’ prediction accuracy is an important milestone.”
However, he emphasized that there is still a great deal of work to be done to determine, for example, if seizure prediction with these devices can be accurate enough to be clinically useful. “For example, if the system generates too many false-positive predictions, patients won’t use it.”
In addition, the findings need to be replicated and recordings extended to 6 months or more to determine whether they are helpful to patients long term and in the home environment, said Dr. Brinkmann.
The investigators and Dr. Brinkmann have disclosed having no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The new findings have the potential to revolutionize the management of patients with epilepsy, according to the researchers. “We have set a first benchmark for automatic detection of a variety of epileptic seizures using wearable sensors and deep-learning algorithms. In other words, we have shown for the first time that it’s possible to do this,” said study investigator Jianbin Tang, MA, data science project lead, IBM Research Australia, Victoria.
The findings were presented at the American Epilepsy Society’s annual meeting, held online this year because of the COVID-19 pandemic.
Accurate monitoring of seizures is important for assessing risk, injury prevention, and treatment response evaluation. Currently, video EEG is the gold standard for seizure detection, but it requires a hospital stay, is often costly, and can be stigmatizing, said Mr. Tang.
An advance in detecting seizure types
Recent advances in non-EEG wearable devices show promise in detecting generalized onset tonic-clonic and focal to bilateral tonic-clonic seizures, but it’s not clear if they have the ability to detect other seizure types. “We hope to fill this gap by expanding wearable seizure detection to additional seizure types,” said Mr. Tang.
Seizure tracking outside the hospital setting largely “relies on manually annotated family and patient reports, which often can be unreliable due to missed seizures and problems recalling seizures,” he said.
The study included 75 children (44% were female; mean age was 11.1 years) admitted to a long-term EEG monitoring unit at a single center for a 24-hour stay. Patients wore the detector on the ankle or wrist. The device continuously collected data on functions such as sweating, heart rate, movement, and temperature.
With part of the dataset, researchers trained deep-learning algorithms to automatically detect seizure segments. They then validated the performance of the detection algorithms on the remainder of the dataset.
The analysis was based on data from 722 epileptic seizures of all types including focal and generalized, motor and nonmotor. Seizures occurred throughout the day and during the night while patients were awake or asleep.
When a seizure is detected, the system triggers a real-time alert and will store the information about the detected seizure in a repository, said Mr. Tang.
The signals were initially stored in the wristband and then securely uploaded to the Cloud. From there, the signal files were downloaded by the investigators for analysis and interpretation. All data were entirely anonymized and de-identified. Researchers used Area Under Curve–Receiver Operating Characteristic (AUC-ROC) to assess performance.
“Our best performing detection models reach an AUC-ROC of 67.59%, which represents a decent performance level,” said Mr. Tang. “There certainly is room for performance improvement and we are already working on this,” he added.
The device performed “better than chance,” which is a “standard technical term” in the field of machine learning and is “the first hurdle any machine-learning model needs to take to be considered useful.” The investigators noted that such automatic seizure detection “is feasible across a broad spectrum of epileptic seizure types,” said Mr. Tang. “This is a first and has not been shown before.”
The study suggests that the noninvasive wearable device could be used at home, at school, and in other everyday settings outside the clinic. “This could one day provide patients, caregivers, and clinicians with reliable seizure reports,” said Mr. Tang.
He said he believes the device might be especially useful in detecting frequent or subtle seizures, which are easy to miss. Patients requiring medication evaluation and rescue medication and those at risk of status epilepticus may be good candidates.
The researchers don’t expect wearable technology to totally replace EEG but see it as “a useful complementary tool to track seizures continuously at times or in settings where EEG monitoring is not available,” said Mr. Tang.
‘Important milestone’
Commenting on the research, Benjamin H. Brinkmann, PhD, associate professor of neurology at the Mayo Clinic in Rochester, Minn., said the investigators “have done very good work applying state of the art machine learning techniques” to the “important problem” of accurately detecting seizures.
Dr. Brinkmann is part of the Epilepsy Foundation–sponsored “My Seizure Gauge” project that’s evaluating various wearable devices, including the Empatica E4 wristband and the Fitbit Charge 3, to determine what measurements are needed for reliable seizure forecasting.
“Previously, no one knew whether seizure prediction was possible with these devices, and the fact that this group was able to achieve ‘better-than-chance’ prediction accuracy is an important milestone.”
However, he emphasized that there is still a great deal of work to be done to determine, for example, if seizure prediction with these devices can be accurate enough to be clinically useful. “For example, if the system generates too many false-positive predictions, patients won’t use it.”
In addition, the findings need to be replicated and recordings extended to 6 months or more to determine whether they are helpful to patients long term and in the home environment, said Dr. Brinkmann.
The investigators and Dr. Brinkmann have disclosed having no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The new findings have the potential to revolutionize the management of patients with epilepsy, according to the researchers. “We have set a first benchmark for automatic detection of a variety of epileptic seizures using wearable sensors and deep-learning algorithms. In other words, we have shown for the first time that it’s possible to do this,” said study investigator Jianbin Tang, MA, data science project lead, IBM Research Australia, Victoria.
The findings were presented at the American Epilepsy Society’s annual meeting, held online this year because of the COVID-19 pandemic.
Accurate monitoring of seizures is important for assessing risk, injury prevention, and treatment response evaluation. Currently, video EEG is the gold standard for seizure detection, but it requires a hospital stay, is often costly, and can be stigmatizing, said Mr. Tang.
An advance in detecting seizure types
Recent advances in non-EEG wearable devices show promise in detecting generalized onset tonic-clonic and focal to bilateral tonic-clonic seizures, but it’s not clear if they have the ability to detect other seizure types. “We hope to fill this gap by expanding wearable seizure detection to additional seizure types,” said Mr. Tang.
Seizure tracking outside the hospital setting largely “relies on manually annotated family and patient reports, which often can be unreliable due to missed seizures and problems recalling seizures,” he said.
The study included 75 children (44% were female; mean age was 11.1 years) admitted to a long-term EEG monitoring unit at a single center for a 24-hour stay. Patients wore the detector on the ankle or wrist. The device continuously collected data on functions such as sweating, heart rate, movement, and temperature.
With part of the dataset, researchers trained deep-learning algorithms to automatically detect seizure segments. They then validated the performance of the detection algorithms on the remainder of the dataset.
The analysis was based on data from 722 epileptic seizures of all types including focal and generalized, motor and nonmotor. Seizures occurred throughout the day and during the night while patients were awake or asleep.
When a seizure is detected, the system triggers a real-time alert and will store the information about the detected seizure in a repository, said Mr. Tang.
The signals were initially stored in the wristband and then securely uploaded to the Cloud. From there, the signal files were downloaded by the investigators for analysis and interpretation. All data were entirely anonymized and de-identified. Researchers used Area Under Curve–Receiver Operating Characteristic (AUC-ROC) to assess performance.
“Our best performing detection models reach an AUC-ROC of 67.59%, which represents a decent performance level,” said Mr. Tang. “There certainly is room for performance improvement and we are already working on this,” he added.
The device performed “better than chance,” which is a “standard technical term” in the field of machine learning and is “the first hurdle any machine-learning model needs to take to be considered useful.” The investigators noted that such automatic seizure detection “is feasible across a broad spectrum of epileptic seizure types,” said Mr. Tang. “This is a first and has not been shown before.”
The study suggests that the noninvasive wearable device could be used at home, at school, and in other everyday settings outside the clinic. “This could one day provide patients, caregivers, and clinicians with reliable seizure reports,” said Mr. Tang.
He said he believes the device might be especially useful in detecting frequent or subtle seizures, which are easy to miss. Patients requiring medication evaluation and rescue medication and those at risk of status epilepticus may be good candidates.
The researchers don’t expect wearable technology to totally replace EEG but see it as “a useful complementary tool to track seizures continuously at times or in settings where EEG monitoring is not available,” said Mr. Tang.
‘Important milestone’
Commenting on the research, Benjamin H. Brinkmann, PhD, associate professor of neurology at the Mayo Clinic in Rochester, Minn., said the investigators “have done very good work applying state of the art machine learning techniques” to the “important problem” of accurately detecting seizures.
Dr. Brinkmann is part of the Epilepsy Foundation–sponsored “My Seizure Gauge” project that’s evaluating various wearable devices, including the Empatica E4 wristband and the Fitbit Charge 3, to determine what measurements are needed for reliable seizure forecasting.
“Previously, no one knew whether seizure prediction was possible with these devices, and the fact that this group was able to achieve ‘better-than-chance’ prediction accuracy is an important milestone.”
However, he emphasized that there is still a great deal of work to be done to determine, for example, if seizure prediction with these devices can be accurate enough to be clinically useful. “For example, if the system generates too many false-positive predictions, patients won’t use it.”
In addition, the findings need to be replicated and recordings extended to 6 months or more to determine whether they are helpful to patients long term and in the home environment, said Dr. Brinkmann.
The investigators and Dr. Brinkmann have disclosed having no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AES 2020
New laser therapy shows promise in children with treatment-resistant epilepsy
A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests.
Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.
In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.
The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
Registry study
To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.
In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.
From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.
All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.
The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.
Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.
The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
Seizure freedom
Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.
Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.
Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.
Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.
There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.
Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.
Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.
Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
‘Very important’ research
Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”
Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.
He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.
“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.
He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.
Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.
The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests.
Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.
In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.
The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
Registry study
To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.
In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.
From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.
All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.
The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.
Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.
The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
Seizure freedom
Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.
Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.
Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.
Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.
There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.
Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.
Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.
Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
‘Very important’ research
Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”
Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.
He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.
“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.
He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.
Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.
The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests.
Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.
In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.
The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
Registry study
To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.
In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.
From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.
All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.
The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.
Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.
The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
Seizure freedom
Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.
Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.
Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.
Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.
There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.
Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.
Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.
Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
‘Very important’ research
Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”
Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.
He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.
“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.
He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.
Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.
The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
From AES 2020