Jake Remaly

CHICAGO—About half of staring spells referred to a new-onset seizure (NOS) clinic turn out to be epileptic seizures, according to a retrospective chart review presented at the 47th Annual Meeting of the Child Neurology Society.

Children with nonepileptic staring were younger and more likely to have developmental delay, compared with children with epileptic staring, said Seunghyo Kim, MD, Visiting Associate Professor of Pediatrics at Emory University School of Medicine in Atlanta, and his colleagues. In addition, children with nonepileptic staring were more likely to have been referred by a primary care physician than by an emergency department.

A Common Reason for Referral

Staring spells are common in children and a frequent reason for referral to NOS clinics, the investigators said. Staring spells may be generalized absence seizures, focal seizures, or nonepileptic events. Few studies, however, have examined patients who newly present to a neurology clinic with the chief complaint of staring spells.

To evaluate the clinical and demographic features of children who present with staring spells to a regional NOS clinic, the researchers reviewed charts from 2,818 patients who visited a children’s hospital between September 22, 2015, and March 19, 2018. The investigators identified 189 patients with staring spells.

They excluded 48 cases where staring was accompanied by or followed by generalized tonic-clonic seizures or other motor seizures. In addition, they excluded 16 cases of established epilepsy and four cases of provoked seizures, including febrile seizures.

The final study population included 121 cases. About 48% of these patients with staring spells were African American, and 38% were white. Patients’ mean age at first visit to the NOS clinic was 6, and mean age at staring spell onset was 5.2.

Fifty-nine patients (49%) had epileptic staring episodes, and 62 patients (51%) had nonepileptic events.

Continue to: Approximately 50% were referred by an emergency department...

MRI Findings in Patients With Focal Seizures

On average, patients with nonepileptic staring were younger at the initial clinic presentation and at staring spell onset. Patients with nonepileptic staring had an average age of 4.8 at their initial visit, whereas patients with focal seizures had an average age of 6.3. Patients with absence seizures had an average age of 8.3.

Patients with nonepileptic events were more likely to have developmental delay (approximately 35%) versus patients with focal seizures (23%) or absence seizures (8%).

Absence epilepsy was diagnosed in 24 patients (20%), and focal epilepsy in 35 patients (29%).

Of the 59 cases of epileptic staring, 46% (n = 27) were classified as syndromic; 36% (n = 21) had childhood absence epilepsy, and 5% (n = 3) had juvenile absence epilepsy. In addition, there was one case each of mesial temporal lobe epilepsy with hippocampal sclerosis, Panayiotopoulos syndrome, and generalized epilepsy with febrile seizures.

About one-third of patients received MRI, and seven patients had etiologically relevant findings (eg, brain tumor, malformation of cortical development, and periventricular leukomalacia). All of the patients with abnormal MRIs had focal seizures.

“An NOS clinic ... can provide rapid, accurate diagnoses for staring spells,” said Dr. Kim. “This is important, as children with nonepileptic events should not be given the diagnosis of epilepsy, and their events should not be treated with seizure medications. Similarly, children who have epileptic seizures require accurate diagnosis, as the treatment depends on the seizure type.”

CHICAGO—About half of staring spells referred to a new-onset seizure (NOS) clinic turn out to be epileptic seizures, according to a retrospective chart review presented at the 47th Annual Meeting of the Child Neurology Society.

Children with nonepileptic staring were younger and more likely to have developmental delay, compared with children with epileptic staring, said Seunghyo Kim, MD, Visiting Associate Professor of Pediatrics at Emory University School of Medicine in Atlanta, and his colleagues. In addition, children with nonepileptic staring were more likely to have been referred by a primary care physician than by an emergency department.

A Common Reason for Referral

Staring spells are common in children and a frequent reason for referral to NOS clinics, the investigators said. Staring spells may be generalized absence seizures, focal seizures, or nonepileptic events. Few studies, however, have examined patients who newly present to a neurology clinic with the chief complaint of staring spells.

To evaluate the clinical and demographic features of children who present with staring spells to a regional NOS clinic, the researchers reviewed charts from 2,818 patients who visited a children’s hospital between September 22, 2015, and March 19, 2018. The investigators identified 189 patients with staring spells.

They excluded 48 cases where staring was accompanied by or followed by generalized tonic-clonic seizures or other motor seizures. In addition, they excluded 16 cases of established epilepsy and four cases of provoked seizures, including febrile seizures.

The final study population included 121 cases. About 48% of these patients with staring spells were African American, and 38% were white. Patients’ mean age at first visit to the NOS clinic was 6, and mean age at staring spell onset was 5.2.

Fifty-nine patients (49%) had epileptic staring episodes, and 62 patients (51%) had nonepileptic events.

Continue to: Approximately 50% were referred by an emergency department...

MRI Findings in Patients With Focal Seizures

On average, patients with nonepileptic staring were younger at the initial clinic presentation and at staring spell onset. Patients with nonepileptic staring had an average age of 4.8 at their initial visit, whereas patients with focal seizures had an average age of 6.3. Patients with absence seizures had an average age of 8.3.

Patients with nonepileptic events were more likely to have developmental delay (approximately 35%) versus patients with focal seizures (23%) or absence seizures (8%).

Absence epilepsy was diagnosed in 24 patients (20%), and focal epilepsy in 35 patients (29%).

Of the 59 cases of epileptic staring, 46% (n = 27) were classified as syndromic; 36% (n = 21) had childhood absence epilepsy, and 5% (n = 3) had juvenile absence epilepsy. In addition, there was one case each of mesial temporal lobe epilepsy with hippocampal sclerosis, Panayiotopoulos syndrome, and generalized epilepsy with febrile seizures.

About one-third of patients received MRI, and seven patients had etiologically relevant findings (eg, brain tumor, malformation of cortical development, and periventricular leukomalacia). All of the patients with abnormal MRIs had focal seizures.

“An NOS clinic ... can provide rapid, accurate diagnoses for staring spells,” said Dr. Kim. “This is important, as children with nonepileptic events should not be given the diagnosis of epilepsy, and their events should not be treated with seizure medications. Similarly, children who have epileptic seizures require accurate diagnosis, as the treatment depends on the seizure type.”

CHICAGO—About half of staring spells referred to a new-onset seizure (NOS) clinic turn out to be epileptic seizures, according to a retrospective chart review presented at the 47th Annual Meeting of the Child Neurology Society.

Children with nonepileptic staring were younger and more likely to have developmental delay, compared with children with epileptic staring, said Seunghyo Kim, MD, Visiting Associate Professor of Pediatrics at Emory University School of Medicine in Atlanta, and his colleagues. In addition, children with nonepileptic staring were more likely to have been referred by a primary care physician than by an emergency department.

A Common Reason for Referral

Staring spells are common in children and a frequent reason for referral to NOS clinics, the investigators said. Staring spells may be generalized absence seizures, focal seizures, or nonepileptic events. Few studies, however, have examined patients who newly present to a neurology clinic with the chief complaint of staring spells.

To evaluate the clinical and demographic features of children who present with staring spells to a regional NOS clinic, the researchers reviewed charts from 2,818 patients who visited a children’s hospital between September 22, 2015, and March 19, 2018. The investigators identified 189 patients with staring spells.

They excluded 48 cases where staring was accompanied by or followed by generalized tonic-clonic seizures or other motor seizures. In addition, they excluded 16 cases of established epilepsy and four cases of provoked seizures, including febrile seizures.

The final study population included 121 cases. About 48% of these patients with staring spells were African American, and 38% were white. Patients’ mean age at first visit to the NOS clinic was 6, and mean age at staring spell onset was 5.2.

Fifty-nine patients (49%) had epileptic staring episodes, and 62 patients (51%) had nonepileptic events.

Continue to: Approximately 50% were referred by an emergency department...

MRI Findings in Patients With Focal Seizures

On average, patients with nonepileptic staring were younger at the initial clinic presentation and at staring spell onset. Patients with nonepileptic staring had an average age of 4.8 at their initial visit, whereas patients with focal seizures had an average age of 6.3. Patients with absence seizures had an average age of 8.3.

Patients with nonepileptic events were more likely to have developmental delay (approximately 35%) versus patients with focal seizures (23%) or absence seizures (8%).

Absence epilepsy was diagnosed in 24 patients (20%), and focal epilepsy in 35 patients (29%).

Of the 59 cases of epileptic staring, 46% (n = 27) were classified as syndromic; 36% (n = 21) had childhood absence epilepsy, and 5% (n = 3) had juvenile absence epilepsy. In addition, there was one case each of mesial temporal lobe epilepsy with hippocampal sclerosis, Panayiotopoulos syndrome, and generalized epilepsy with febrile seizures.

About one-third of patients received MRI, and seven patients had etiologically relevant findings (eg, brain tumor, malformation of cortical development, and periventricular leukomalacia). All of the patients with abnormal MRIs had focal seizures.

“An NOS clinic ... can provide rapid, accurate diagnoses for staring spells,” said Dr. Kim. “This is important, as children with nonepileptic events should not be given the diagnosis of epilepsy, and their events should not be treated with seizure medications. Similarly, children who have epileptic seizures require accurate diagnosis, as the treatment depends on the seizure type.”

The efficacy and side effects of cannabidiol (CBD) in severe pediatric epilepsies are similar to those of other antiepileptic drugs (AEDs), according to a review published in Developmental Medicine & Child Neurology. “Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD,” the authors said.

Although CBD’s antiepileptic mechanisms “are not fully elucidated, it is clear that administration of CBD as adjunct therapy decreases seizure frequency in patients with Dravet syndrome and Lennox-Gastaut syndrome,” wrote Shayma Ali, a doctoral student in the department of pediatrics and child health at the University of Otago in Wellington, New Zealand, and her colleagues. “Contrary to public expectation of miraculous results, CBD has a similar antiepileptic and side effect profile to other AEDs. Nevertheless, as individual children with these developmental and epileptic encephalopathies are often refractory to available AEDs, the addition of another potentially effective therapeutic medicine will be warmly welcomed by families and physicians.”

The FDA approved Epidiolex, a pharmaceutical-grade oral solution that is 98% CBD, in June of 2018. In September of 2018, the Drug Enforcement Administration classified it as a Schedule V controlled substance. Patients’ use of nonpharmaceutical grade CBD products, including those combined with tetrahydrocannabinol (THC), “raises concerns about the use of products with THC on the developing brain,” the review authors said.
 

Randomized trials

Three randomized, controlled, double-blind trials in patients with Dravet syndrome and Lennox-Gastaut syndrome found that CBD, compared with placebo, results in greater median seizure reductions (38%-41% vs. 13%-19%) and responder rates (i.e., the proportion of patients with 50% reductions in convulsive or drop seizures; 39%-46% vs. 14%-27%).

Common adverse effects include somnolence, diarrhea, decreased appetite, fatigue, lethargy, pyrexia, and vomiting. Hepatic transaminases became elevated in some patients, and this result occurred more often in patients taking valproate.

No phase 2 or phase 3 trials have assessed the efficacy of CBD without coadministration of other AEDs, and CBD’s efficacy may relate to its impact on the pharmacokinetics of coadministered AEDs. “The most important clinical interaction is between CBD and clobazam, as [the dose of] clobazam often needs to be lowered because of excessive sedation,” wrote Ms. Ali and her colleagues. CBD inhibits CYP2C19 and CYP3A4 – enzymes that are involved in clobazam metabolism – which results in high plasma concentrations of clobazam’s active metabolite, norclobazam. Plasma levels of topiramate, rufinamide, zonisamide, and eslicarbazepine also may increase when these drugs are taken with CBD.
 

Challenges and opportunities

Of the hundreds of compounds in the marijuana plant, CBD “has the most evidence of antiepileptic efficacy and does not have the psychoactive effects” of THC, the authors said. Little evidence supports the combination of THC and CBD for the treatment of epilepsy. In addition, research indicates that THC can have a proconvulsive effect in animal models and harm the development of the human brain.

Investigators are evaluating alternative routes of CBD delivery to avoid first-pass metabolism, such as oromucosal sprays, transdermal gels, eye drops, intranasal sprays, and rectal suppositories. “Alternative methods of administration ... deserve consideration, particularly for the developmental and epileptic encephalopathies population, as administration of oral medication can be challenging,” they said.

[email protected]

SOURCE: Ali S et al. Dev Med Child Neurol. 2018. doi: 10.1111/dmcn.14087.

The efficacy and side effects of cannabidiol (CBD) in severe pediatric epilepsies are similar to those of other antiepileptic drugs (AEDs), according to a review published in Developmental Medicine & Child Neurology. “Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD,” the authors said.

Although CBD’s antiepileptic mechanisms “are not fully elucidated, it is clear that administration of CBD as adjunct therapy decreases seizure frequency in patients with Dravet syndrome and Lennox-Gastaut syndrome,” wrote Shayma Ali, a doctoral student in the department of pediatrics and child health at the University of Otago in Wellington, New Zealand, and her colleagues. “Contrary to public expectation of miraculous results, CBD has a similar antiepileptic and side effect profile to other AEDs. Nevertheless, as individual children with these developmental and epileptic encephalopathies are often refractory to available AEDs, the addition of another potentially effective therapeutic medicine will be warmly welcomed by families and physicians.”

The FDA approved Epidiolex, a pharmaceutical-grade oral solution that is 98% CBD, in June of 2018. In September of 2018, the Drug Enforcement Administration classified it as a Schedule V controlled substance. Patients’ use of nonpharmaceutical grade CBD products, including those combined with tetrahydrocannabinol (THC), “raises concerns about the use of products with THC on the developing brain,” the review authors said.
 

Randomized trials

Three randomized, controlled, double-blind trials in patients with Dravet syndrome and Lennox-Gastaut syndrome found that CBD, compared with placebo, results in greater median seizure reductions (38%-41% vs. 13%-19%) and responder rates (i.e., the proportion of patients with 50% reductions in convulsive or drop seizures; 39%-46% vs. 14%-27%).

Common adverse effects include somnolence, diarrhea, decreased appetite, fatigue, lethargy, pyrexia, and vomiting. Hepatic transaminases became elevated in some patients, and this result occurred more often in patients taking valproate.

No phase 2 or phase 3 trials have assessed the efficacy of CBD without coadministration of other AEDs, and CBD’s efficacy may relate to its impact on the pharmacokinetics of coadministered AEDs. “The most important clinical interaction is between CBD and clobazam, as [the dose of] clobazam often needs to be lowered because of excessive sedation,” wrote Ms. Ali and her colleagues. CBD inhibits CYP2C19 and CYP3A4 – enzymes that are involved in clobazam metabolism – which results in high plasma concentrations of clobazam’s active metabolite, norclobazam. Plasma levels of topiramate, rufinamide, zonisamide, and eslicarbazepine also may increase when these drugs are taken with CBD.
 

Challenges and opportunities

Of the hundreds of compounds in the marijuana plant, CBD “has the most evidence of antiepileptic efficacy and does not have the psychoactive effects” of THC, the authors said. Little evidence supports the combination of THC and CBD for the treatment of epilepsy. In addition, research indicates that THC can have a proconvulsive effect in animal models and harm the development of the human brain.

Investigators are evaluating alternative routes of CBD delivery to avoid first-pass metabolism, such as oromucosal sprays, transdermal gels, eye drops, intranasal sprays, and rectal suppositories. “Alternative methods of administration ... deserve consideration, particularly for the developmental and epileptic encephalopathies population, as administration of oral medication can be challenging,” they said.

[email protected]

SOURCE: Ali S et al. Dev Med Child Neurol. 2018. doi: 10.1111/dmcn.14087.

The efficacy and side effects of cannabidiol (CBD) in severe pediatric epilepsies are similar to those of other antiepileptic drugs (AEDs), according to a review published in Developmental Medicine & Child Neurology. “Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD,” the authors said.

Although CBD’s antiepileptic mechanisms “are not fully elucidated, it is clear that administration of CBD as adjunct therapy decreases seizure frequency in patients with Dravet syndrome and Lennox-Gastaut syndrome,” wrote Shayma Ali, a doctoral student in the department of pediatrics and child health at the University of Otago in Wellington, New Zealand, and her colleagues. “Contrary to public expectation of miraculous results, CBD has a similar antiepileptic and side effect profile to other AEDs. Nevertheless, as individual children with these developmental and epileptic encephalopathies are often refractory to available AEDs, the addition of another potentially effective therapeutic medicine will be warmly welcomed by families and physicians.”

The FDA approved Epidiolex, a pharmaceutical-grade oral solution that is 98% CBD, in June of 2018. In September of 2018, the Drug Enforcement Administration classified it as a Schedule V controlled substance. Patients’ use of nonpharmaceutical grade CBD products, including those combined with tetrahydrocannabinol (THC), “raises concerns about the use of products with THC on the developing brain,” the review authors said.
 

Randomized trials

Three randomized, controlled, double-blind trials in patients with Dravet syndrome and Lennox-Gastaut syndrome found that CBD, compared with placebo, results in greater median seizure reductions (38%-41% vs. 13%-19%) and responder rates (i.e., the proportion of patients with 50% reductions in convulsive or drop seizures; 39%-46% vs. 14%-27%).

Common adverse effects include somnolence, diarrhea, decreased appetite, fatigue, lethargy, pyrexia, and vomiting. Hepatic transaminases became elevated in some patients, and this result occurred more often in patients taking valproate.

No phase 2 or phase 3 trials have assessed the efficacy of CBD without coadministration of other AEDs, and CBD’s efficacy may relate to its impact on the pharmacokinetics of coadministered AEDs. “The most important clinical interaction is between CBD and clobazam, as [the dose of] clobazam often needs to be lowered because of excessive sedation,” wrote Ms. Ali and her colleagues. CBD inhibits CYP2C19 and CYP3A4 – enzymes that are involved in clobazam metabolism – which results in high plasma concentrations of clobazam’s active metabolite, norclobazam. Plasma levels of topiramate, rufinamide, zonisamide, and eslicarbazepine also may increase when these drugs are taken with CBD.
 

Challenges and opportunities

Of the hundreds of compounds in the marijuana plant, CBD “has the most evidence of antiepileptic efficacy and does not have the psychoactive effects” of THC, the authors said. Little evidence supports the combination of THC and CBD for the treatment of epilepsy. In addition, research indicates that THC can have a proconvulsive effect in animal models and harm the development of the human brain.

Investigators are evaluating alternative routes of CBD delivery to avoid first-pass metabolism, such as oromucosal sprays, transdermal gels, eye drops, intranasal sprays, and rectal suppositories. “Alternative methods of administration ... deserve consideration, particularly for the developmental and epileptic encephalopathies population, as administration of oral medication can be challenging,” they said.

[email protected]

SOURCE: Ali S et al. Dev Med Child Neurol. 2018. doi: 10.1111/dmcn.14087.

NEW ORLEANS – More than 30% of patients with newly diagnosed epilepsy do not initiate antiepileptic drug (AED) treatment at the time of diagnosis, according to an Australian study presented at the annual meeting of the American Epilepsy Society. Most untreated patients begin an AED after experiencing subsequent seizures, however.

“The decision to start or withhold treatment reflects the complex interplay between factors perceived to influence the predicted risk of seizure recurrence, which remain imprecise, and personal factors,” said lead study author Zhibin Chen, PhD, a biostatistician at the University of Melbourne and colleagues.

Many patients with epilepsy in resource-poor countries may not receive AED therapy for socioeconomic reasons, but little is known about untreated epilepsy in high-income countries. To assess the extent of and reasons for patients not receiving AEDs when treatment is accessible and affordable, Dr. Chen and colleagues prospectively recruited adult patients who attended the first-seizure clinics of publicly funded hospitals in Western Australia between May 1, 1999, and May 31, 2016. The patients had new-onset seizures and were referred by primary care or emergency department physicians. The health care system provided universal coverage for patients’ hospital admissions, outpatient visits, investigations, and treatment.

The researchers identified patients with newly diagnosed epilepsy and reviewed medical records to determine the proportion of untreated patients and the reasons for not starting treatment at each follow-up visit. The investigators compared the sociodemographic factors, neuroimaging, and EEG findings of treated and untreated patients.

In all, 1,317 people attended the clinics during the study period, and 610 patients (61% male; median age, 40) received a diagnosis of epilepsy and met 2014 International League Against Epilepsy (ILAE) diagnostic criteria for epilepsy. Patients were followed for a median of 5.7 years.

Of the 610 patients with epilepsy, 31% did not start AED treatment at the time of diagnosis – 16.4% because the neurologist did not recommend treatment and 14.6% because the patient declined treatment despite a neurologist’s recommendation to start therapy.

Patients’ reasons for not starting treatment included doubts about the need for treatment or about the epilepsy diagnosis, as well as concerns about medication side effects. Neurologists’ reasons for not beginning treatment included a patient having only one seizure and awaiting further results. The presence of seizure-precipitating factors (e.g., flashing lights, sleep deprivation, stress, or alcohol use) was another reason that patients and neurologists commonly cited for not initiating treatment.

Among the 189 initially untreated patients, 62.4% started treatment after a median delay of 95 days, “mainly after further seizures,” the investigators said. Patients with epilepsy who were older, from lower socioeconomic areas, had experienced more seizures, or had epileptogenic lesions on neuroimaging were more likely to initiate AED treatment at diagnosis.

“The percentage of people who were not initially prescribed AEDs was much higher than expected and suggests that untreated epilepsy exists not just in resource-poor, but also in wealthy countries,” said Dr. Chen.

More research is needed to assess the long-term outcomes of patient with seizure-precipitating factors who initiate AEDs immediately, compared with those who try avoidance of precipitating factors alone, said Dr. Chen.

This study was supported by a grant from UCB Pharma.

[email protected]

SOURCE: Chen Z et al. AES 2018, Abstract 3.421.

NEW ORLEANS – More than 30% of patients with newly diagnosed epilepsy do not initiate antiepileptic drug (AED) treatment at the time of diagnosis, according to an Australian study presented at the annual meeting of the American Epilepsy Society. Most untreated patients begin an AED after experiencing subsequent seizures, however.

“The decision to start or withhold treatment reflects the complex interplay between factors perceived to influence the predicted risk of seizure recurrence, which remain imprecise, and personal factors,” said lead study author Zhibin Chen, PhD, a biostatistician at the University of Melbourne and colleagues.

Many patients with epilepsy in resource-poor countries may not receive AED therapy for socioeconomic reasons, but little is known about untreated epilepsy in high-income countries. To assess the extent of and reasons for patients not receiving AEDs when treatment is accessible and affordable, Dr. Chen and colleagues prospectively recruited adult patients who attended the first-seizure clinics of publicly funded hospitals in Western Australia between May 1, 1999, and May 31, 2016. The patients had new-onset seizures and were referred by primary care or emergency department physicians. The health care system provided universal coverage for patients’ hospital admissions, outpatient visits, investigations, and treatment.

The researchers identified patients with newly diagnosed epilepsy and reviewed medical records to determine the proportion of untreated patients and the reasons for not starting treatment at each follow-up visit. The investigators compared the sociodemographic factors, neuroimaging, and EEG findings of treated and untreated patients.

In all, 1,317 people attended the clinics during the study period, and 610 patients (61% male; median age, 40) received a diagnosis of epilepsy and met 2014 International League Against Epilepsy (ILAE) diagnostic criteria for epilepsy. Patients were followed for a median of 5.7 years.

Of the 610 patients with epilepsy, 31% did not start AED treatment at the time of diagnosis – 16.4% because the neurologist did not recommend treatment and 14.6% because the patient declined treatment despite a neurologist’s recommendation to start therapy.

Patients’ reasons for not starting treatment included doubts about the need for treatment or about the epilepsy diagnosis, as well as concerns about medication side effects. Neurologists’ reasons for not beginning treatment included a patient having only one seizure and awaiting further results. The presence of seizure-precipitating factors (e.g., flashing lights, sleep deprivation, stress, or alcohol use) was another reason that patients and neurologists commonly cited for not initiating treatment.

Among the 189 initially untreated patients, 62.4% started treatment after a median delay of 95 days, “mainly after further seizures,” the investigators said. Patients with epilepsy who were older, from lower socioeconomic areas, had experienced more seizures, or had epileptogenic lesions on neuroimaging were more likely to initiate AED treatment at diagnosis.

“The percentage of people who were not initially prescribed AEDs was much higher than expected and suggests that untreated epilepsy exists not just in resource-poor, but also in wealthy countries,” said Dr. Chen.

More research is needed to assess the long-term outcomes of patient with seizure-precipitating factors who initiate AEDs immediately, compared with those who try avoidance of precipitating factors alone, said Dr. Chen.

This study was supported by a grant from UCB Pharma.

[email protected]

SOURCE: Chen Z et al. AES 2018, Abstract 3.421.

NEW ORLEANS – More than 30% of patients with newly diagnosed epilepsy do not initiate antiepileptic drug (AED) treatment at the time of diagnosis, according to an Australian study presented at the annual meeting of the American Epilepsy Society. Most untreated patients begin an AED after experiencing subsequent seizures, however.

“The decision to start or withhold treatment reflects the complex interplay between factors perceived to influence the predicted risk of seizure recurrence, which remain imprecise, and personal factors,” said lead study author Zhibin Chen, PhD, a biostatistician at the University of Melbourne and colleagues.

Many patients with epilepsy in resource-poor countries may not receive AED therapy for socioeconomic reasons, but little is known about untreated epilepsy in high-income countries. To assess the extent of and reasons for patients not receiving AEDs when treatment is accessible and affordable, Dr. Chen and colleagues prospectively recruited adult patients who attended the first-seizure clinics of publicly funded hospitals in Western Australia between May 1, 1999, and May 31, 2016. The patients had new-onset seizures and were referred by primary care or emergency department physicians. The health care system provided universal coverage for patients’ hospital admissions, outpatient visits, investigations, and treatment.

The researchers identified patients with newly diagnosed epilepsy and reviewed medical records to determine the proportion of untreated patients and the reasons for not starting treatment at each follow-up visit. The investigators compared the sociodemographic factors, neuroimaging, and EEG findings of treated and untreated patients.

In all, 1,317 people attended the clinics during the study period, and 610 patients (61% male; median age, 40) received a diagnosis of epilepsy and met 2014 International League Against Epilepsy (ILAE) diagnostic criteria for epilepsy. Patients were followed for a median of 5.7 years.

Of the 610 patients with epilepsy, 31% did not start AED treatment at the time of diagnosis – 16.4% because the neurologist did not recommend treatment and 14.6% because the patient declined treatment despite a neurologist’s recommendation to start therapy.

Patients’ reasons for not starting treatment included doubts about the need for treatment or about the epilepsy diagnosis, as well as concerns about medication side effects. Neurologists’ reasons for not beginning treatment included a patient having only one seizure and awaiting further results. The presence of seizure-precipitating factors (e.g., flashing lights, sleep deprivation, stress, or alcohol use) was another reason that patients and neurologists commonly cited for not initiating treatment.

Among the 189 initially untreated patients, 62.4% started treatment after a median delay of 95 days, “mainly after further seizures,” the investigators said. Patients with epilepsy who were older, from lower socioeconomic areas, had experienced more seizures, or had epileptogenic lesions on neuroimaging were more likely to initiate AED treatment at diagnosis.

“The percentage of people who were not initially prescribed AEDs was much higher than expected and suggests that untreated epilepsy exists not just in resource-poor, but also in wealthy countries,” said Dr. Chen.

More research is needed to assess the long-term outcomes of patient with seizure-precipitating factors who initiate AEDs immediately, compared with those who try avoidance of precipitating factors alone, said Dr. Chen.

This study was supported by a grant from UCB Pharma.

[email protected]

SOURCE: Chen Z et al. AES 2018, Abstract 3.421.

NEW ORLEANS – Adults with focal epilepsy experience a range of disturbing symptoms and functional impacts of the disease, according to a study presented at the annual meeting of the American Epilepsy Society. The most prominent symptoms and effects on daily life may differ in the early, middle, and late stages of the disease, the results suggest.

Lead study author Jacqueline A. French, MD, professor of neurology at New York University, and her colleagues interviewed 62 patients with focal-onset epilepsy to examine patients’ experiences living with epilepsy. The investigators focused on salient symptoms and functional impacts – those that were reported by at least 50% of patients and were associated with a high degree of disturbance (patients rated them 5 or greater on a scale from 0 [no disturbance] to 10 [high disturbance]).

Of 51 symptoms that patients described during the interviews, the following 8 met the salience criteria for the total cohort: twitching or tremors, confusion, difficulty in talking, loss of awareness of others’ presence, stiffening, impaired consciousness or loss of consciousness, difficulty in remembering, and dizziness or lightheadedness. Patients reported salient functional impacts on driving and transportation, work and school, and leisure and social activities. Some symptoms met salience criteria among patients in certain stages of the disease (for example, tongue biting in patients with early-stage epilepsy and anxiety, fear, or panic in late-stage epilepsy) but not among patients in the other cohorts.

“These findings underscore the need to consider all these experiences when developing patient-reported outcome measures for use in clinical trials,” said Dr. French and her colleagues. “It may be useful to tailor measures of patient experiences to the patient’s stage of disease.”

Previous qualitative studies of epilepsy symptoms and burdens were based on small numbers of patients and interviews at a single center. For the present study, the researchers conducted qualitative, semistructured, in-person interviews with adults with focal epilepsy in different areas of the United States (such as California, Minnesota, New York, Ohio, and Pennsylvania). Patients were grouped by early, middle, or late disease stage. Patients in the early cohort (n = 19) had at least two seizures in the past year, a diagnosis of focal epilepsy in the past year, and had not yet received antiepileptic drug (AED) treatment or had received treatment with only one AED and had not failed treatment. Patients in the middle cohort (n = 17) had at least one seizure in the past year, a diagnosis of focal epilepsy within the past 5 years, and had failed one AED because of lack of efficacy or had received their first add-on AED. Patients in the late cohort (n = 26) had at least one seizure every 3 months during the past year, a diagnosis of focal epilepsy at age 12 years or older, and inadequate response to treatment of at least 3 months with two AEDs that were tolerated and appropriately chosen.

Patients’ mean age was 37 years (range, 19-60 years), 73% were female, 79% were white, 69% had a college degree as their highest level of education, and 65% were employed. Patients’ seizure types included simple partial without motor signs (52%), simple partial with motor signs (16%), complex partial (68%), or secondarily generalized (65%).

While driving or transportation was a salient impact for all three groups, memory loss was a salient impact in the early and middle cohorts only. Headaches and sadness or depression were salient impacts for the late cohort only.

This study was funded by Eisai and two of the authors are former or current employees of Eisai.

[email protected]

SOURCE: French JA et al. AES 2018, Abstract 1.196.

NEW ORLEANS – Adults with focal epilepsy experience a range of disturbing symptoms and functional impacts of the disease, according to a study presented at the annual meeting of the American Epilepsy Society. The most prominent symptoms and effects on daily life may differ in the early, middle, and late stages of the disease, the results suggest.

Lead study author Jacqueline A. French, MD, professor of neurology at New York University, and her colleagues interviewed 62 patients with focal-onset epilepsy to examine patients’ experiences living with epilepsy. The investigators focused on salient symptoms and functional impacts – those that were reported by at least 50% of patients and were associated with a high degree of disturbance (patients rated them 5 or greater on a scale from 0 [no disturbance] to 10 [high disturbance]).

Of 51 symptoms that patients described during the interviews, the following 8 met the salience criteria for the total cohort: twitching or tremors, confusion, difficulty in talking, loss of awareness of others’ presence, stiffening, impaired consciousness or loss of consciousness, difficulty in remembering, and dizziness or lightheadedness. Patients reported salient functional impacts on driving and transportation, work and school, and leisure and social activities. Some symptoms met salience criteria among patients in certain stages of the disease (for example, tongue biting in patients with early-stage epilepsy and anxiety, fear, or panic in late-stage epilepsy) but not among patients in the other cohorts.

“These findings underscore the need to consider all these experiences when developing patient-reported outcome measures for use in clinical trials,” said Dr. French and her colleagues. “It may be useful to tailor measures of patient experiences to the patient’s stage of disease.”

Previous qualitative studies of epilepsy symptoms and burdens were based on small numbers of patients and interviews at a single center. For the present study, the researchers conducted qualitative, semistructured, in-person interviews with adults with focal epilepsy in different areas of the United States (such as California, Minnesota, New York, Ohio, and Pennsylvania). Patients were grouped by early, middle, or late disease stage. Patients in the early cohort (n = 19) had at least two seizures in the past year, a diagnosis of focal epilepsy in the past year, and had not yet received antiepileptic drug (AED) treatment or had received treatment with only one AED and had not failed treatment. Patients in the middle cohort (n = 17) had at least one seizure in the past year, a diagnosis of focal epilepsy within the past 5 years, and had failed one AED because of lack of efficacy or had received their first add-on AED. Patients in the late cohort (n = 26) had at least one seizure every 3 months during the past year, a diagnosis of focal epilepsy at age 12 years or older, and inadequate response to treatment of at least 3 months with two AEDs that were tolerated and appropriately chosen.

Patients’ mean age was 37 years (range, 19-60 years), 73% were female, 79% were white, 69% had a college degree as their highest level of education, and 65% were employed. Patients’ seizure types included simple partial without motor signs (52%), simple partial with motor signs (16%), complex partial (68%), or secondarily generalized (65%).

While driving or transportation was a salient impact for all three groups, memory loss was a salient impact in the early and middle cohorts only. Headaches and sadness or depression were salient impacts for the late cohort only.

This study was funded by Eisai and two of the authors are former or current employees of Eisai.

[email protected]

SOURCE: French JA et al. AES 2018, Abstract 1.196.

NEW ORLEANS – Adults with focal epilepsy experience a range of disturbing symptoms and functional impacts of the disease, according to a study presented at the annual meeting of the American Epilepsy Society. The most prominent symptoms and effects on daily life may differ in the early, middle, and late stages of the disease, the results suggest.

Lead study author Jacqueline A. French, MD, professor of neurology at New York University, and her colleagues interviewed 62 patients with focal-onset epilepsy to examine patients’ experiences living with epilepsy. The investigators focused on salient symptoms and functional impacts – those that were reported by at least 50% of patients and were associated with a high degree of disturbance (patients rated them 5 or greater on a scale from 0 [no disturbance] to 10 [high disturbance]).

Of 51 symptoms that patients described during the interviews, the following 8 met the salience criteria for the total cohort: twitching or tremors, confusion, difficulty in talking, loss of awareness of others’ presence, stiffening, impaired consciousness or loss of consciousness, difficulty in remembering, and dizziness or lightheadedness. Patients reported salient functional impacts on driving and transportation, work and school, and leisure and social activities. Some symptoms met salience criteria among patients in certain stages of the disease (for example, tongue biting in patients with early-stage epilepsy and anxiety, fear, or panic in late-stage epilepsy) but not among patients in the other cohorts.

“These findings underscore the need to consider all these experiences when developing patient-reported outcome measures for use in clinical trials,” said Dr. French and her colleagues. “It may be useful to tailor measures of patient experiences to the patient’s stage of disease.”

Previous qualitative studies of epilepsy symptoms and burdens were based on small numbers of patients and interviews at a single center. For the present study, the researchers conducted qualitative, semistructured, in-person interviews with adults with focal epilepsy in different areas of the United States (such as California, Minnesota, New York, Ohio, and Pennsylvania). Patients were grouped by early, middle, or late disease stage. Patients in the early cohort (n = 19) had at least two seizures in the past year, a diagnosis of focal epilepsy in the past year, and had not yet received antiepileptic drug (AED) treatment or had received treatment with only one AED and had not failed treatment. Patients in the middle cohort (n = 17) had at least one seizure in the past year, a diagnosis of focal epilepsy within the past 5 years, and had failed one AED because of lack of efficacy or had received their first add-on AED. Patients in the late cohort (n = 26) had at least one seizure every 3 months during the past year, a diagnosis of focal epilepsy at age 12 years or older, and inadequate response to treatment of at least 3 months with two AEDs that were tolerated and appropriately chosen.

Patients’ mean age was 37 years (range, 19-60 years), 73% were female, 79% were white, 69% had a college degree as their highest level of education, and 65% were employed. Patients’ seizure types included simple partial without motor signs (52%), simple partial with motor signs (16%), complex partial (68%), or secondarily generalized (65%).

While driving or transportation was a salient impact for all three groups, memory loss was a salient impact in the early and middle cohorts only. Headaches and sadness or depression were salient impacts for the late cohort only.

This study was funded by Eisai and two of the authors are former or current employees of Eisai.

[email protected]

SOURCE: French JA et al. AES 2018, Abstract 1.196.

NEW ORLEANS – Patients with epilepsy with gene variants in subunits of the neuronal nicotinic acetylcholine receptor (nAChR) may benefit from treatment with a nicotine patch, according to research presented at the annual meeting of the American Epilepsy Society. Of four epilepsy patients at one center who received nicotine-patch treatment, three had a good clinical response, one of whom became seizure free.

“We confirm that, in select patients, treatment with a nicotine patch ... can be an effective precision therapy for epilepsy. We propose consideration of nicotine-patch treatment in refractory patients with known cholinergic nicotine receptor subunit variants, especially those with a clinical history consistent with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE),” said Jordana Fox, DO, and Alison Dolce, MD, both with the University of Texas Southwestern Medical Center in Dallas.

Gene variants in CHRAn4,CHRNA2, and CHRNB2 can cause ADNFLE. Preclinical and n-of-1 studies have suggested that nicotine may be a precision treatment for ADNFLE.

Dr. Fox and Dr. Dolce reviewed next-generation sequencing epilepsy panels from patients seen at Children’s Medical Center, Dallas, during 2011-2015 to identify patients with nAChR gene variants (CHNRA4, CHRNA2, CHRNB2, and CHRNA7). They reviewed patients’ medical and laboratory records, including genetic variant details and treatment history, and focused on patients who underwent a trial of nicotine-patch treatment.

Of the 21 patients who had nAChR gene variants, 4 tried treatment with a nicotine patch, either 7 mg or 14 mg. The patients who received nicotine-patch treatment had genetic variants in CHRNA4, CHRNB2, and CHRNA2. Three of the patients who tried nicotine-patch treatment had a greater than 50% reduction in seizures, whereas one had no treatment response.

“One patient became seizure free and is now treated with the nicotine patch as monotherapy,” Dr. Fox said.

The patient with complete resolution of seizures had a heterozygous disease–causing mutation in CHRNB2. This patient had nocturnal focal seizures, normal neuroimaging, and had been receiving treatment with oxcarbazepine and zonisamide.

The review identified four patients with nAChR gene variants and the ADNFLE phenotype who have not been treated with nicotine. Further phenotype-genotype characterizations and preclinical studies will help neurologists understand the mechanisms of these complex gene variants.

The researchers received no funding for the study and had no relevant financial disclosures.
 

[email protected]

SOURCE: Fox J et al. AES 2018, Abstract 1.230.

NEW ORLEANS – Patients with epilepsy with gene variants in subunits of the neuronal nicotinic acetylcholine receptor (nAChR) may benefit from treatment with a nicotine patch, according to research presented at the annual meeting of the American Epilepsy Society. Of four epilepsy patients at one center who received nicotine-patch treatment, three had a good clinical response, one of whom became seizure free.

“We confirm that, in select patients, treatment with a nicotine patch ... can be an effective precision therapy for epilepsy. We propose consideration of nicotine-patch treatment in refractory patients with known cholinergic nicotine receptor subunit variants, especially those with a clinical history consistent with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE),” said Jordana Fox, DO, and Alison Dolce, MD, both with the University of Texas Southwestern Medical Center in Dallas.

Gene variants in CHRAn4,CHRNA2, and CHRNB2 can cause ADNFLE. Preclinical and n-of-1 studies have suggested that nicotine may be a precision treatment for ADNFLE.

Dr. Fox and Dr. Dolce reviewed next-generation sequencing epilepsy panels from patients seen at Children’s Medical Center, Dallas, during 2011-2015 to identify patients with nAChR gene variants (CHNRA4, CHRNA2, CHRNB2, and CHRNA7). They reviewed patients’ medical and laboratory records, including genetic variant details and treatment history, and focused on patients who underwent a trial of nicotine-patch treatment.

Of the 21 patients who had nAChR gene variants, 4 tried treatment with a nicotine patch, either 7 mg or 14 mg. The patients who received nicotine-patch treatment had genetic variants in CHRNA4, CHRNB2, and CHRNA2. Three of the patients who tried nicotine-patch treatment had a greater than 50% reduction in seizures, whereas one had no treatment response.

“One patient became seizure free and is now treated with the nicotine patch as monotherapy,” Dr. Fox said.

The patient with complete resolution of seizures had a heterozygous disease–causing mutation in CHRNB2. This patient had nocturnal focal seizures, normal neuroimaging, and had been receiving treatment with oxcarbazepine and zonisamide.

The review identified four patients with nAChR gene variants and the ADNFLE phenotype who have not been treated with nicotine. Further phenotype-genotype characterizations and preclinical studies will help neurologists understand the mechanisms of these complex gene variants.

The researchers received no funding for the study and had no relevant financial disclosures.
 

[email protected]

SOURCE: Fox J et al. AES 2018, Abstract 1.230.

NEW ORLEANS – Patients with epilepsy with gene variants in subunits of the neuronal nicotinic acetylcholine receptor (nAChR) may benefit from treatment with a nicotine patch, according to research presented at the annual meeting of the American Epilepsy Society. Of four epilepsy patients at one center who received nicotine-patch treatment, three had a good clinical response, one of whom became seizure free.

“We confirm that, in select patients, treatment with a nicotine patch ... can be an effective precision therapy for epilepsy. We propose consideration of nicotine-patch treatment in refractory patients with known cholinergic nicotine receptor subunit variants, especially those with a clinical history consistent with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE),” said Jordana Fox, DO, and Alison Dolce, MD, both with the University of Texas Southwestern Medical Center in Dallas.

Gene variants in CHRAn4,CHRNA2, and CHRNB2 can cause ADNFLE. Preclinical and n-of-1 studies have suggested that nicotine may be a precision treatment for ADNFLE.

Dr. Fox and Dr. Dolce reviewed next-generation sequencing epilepsy panels from patients seen at Children’s Medical Center, Dallas, during 2011-2015 to identify patients with nAChR gene variants (CHNRA4, CHRNA2, CHRNB2, and CHRNA7). They reviewed patients’ medical and laboratory records, including genetic variant details and treatment history, and focused on patients who underwent a trial of nicotine-patch treatment.

Of the 21 patients who had nAChR gene variants, 4 tried treatment with a nicotine patch, either 7 mg or 14 mg. The patients who received nicotine-patch treatment had genetic variants in CHRNA4, CHRNB2, and CHRNA2. Three of the patients who tried nicotine-patch treatment had a greater than 50% reduction in seizures, whereas one had no treatment response.

“One patient became seizure free and is now treated with the nicotine patch as monotherapy,” Dr. Fox said.

The patient with complete resolution of seizures had a heterozygous disease–causing mutation in CHRNB2. This patient had nocturnal focal seizures, normal neuroimaging, and had been receiving treatment with oxcarbazepine and zonisamide.

The review identified four patients with nAChR gene variants and the ADNFLE phenotype who have not been treated with nicotine. Further phenotype-genotype characterizations and preclinical studies will help neurologists understand the mechanisms of these complex gene variants.

The researchers received no funding for the study and had no relevant financial disclosures.
 

[email protected]

SOURCE: Fox J et al. AES 2018, Abstract 1.230.

NEW ORLEANS – Seizure frequency increased during pregnancy for 53% of women with frontal lobe epilepsy, based on a study reported by Paula E. Voinescu, MD, PhD, at the annual meeting of the American Epilepsy Society.

Jacob Remaly/MDedge News

The single center study included data on 76 pregnancies in women with focal epilepsy –17 of them in patients with frontal lobe epilepsy – and 38 pregnancies in women with generalized epilepsy. Seizures were more frequent during pregnancy, compared with baseline, in 5.5% of women with generalized epilepsy, 22.6% of women with focal epilepsies, and 53.0% of women with frontal lobe epilepsy, said Dr. Voinescu, lead author of the study and a neurologist at Brigham and Women’s Hospital in Boston.

“Frontal lobe epilepsy is known to be difficult to manage in general and often resistant to therapy, but it isn’t clear why the seizures got worse among pregnant women because the levels of medication in their blood was considered adequate. Until more research provides treatment guidance, doctors should carefully monitor their pregnant patients who have focal epilepsy to see if their seizures increase despite adequate blood levels and then adjust their medication if necessary,” she advised. “As we know from other research, seizures during pregnancy can increase the risk of distress and neurodevelopmental delays for the baby, as well as the risk of miscarriage.”

For the study, Dr. Voinescu and her colleagues analyzed prospectively collected clinical data from 99 pregnant women followed at Brigham and Women’s Hospital between 2013 and 2018.

The researchers excluded patients with abortions, seizure onset during pregnancy, poorly defined preconception seizure frequency, nonepileptic seizures, antiepileptic drug (AED) noncompliance, and pregnancies that were enrolled in other studies. The investigators documented patients’ seizure types and AED regimens and recorded seizure frequency during the 9 months before conception, during pregnancy, and 9 months postpartum. The researchers summed all seizures for each individual for each interval. They defined seizure frequency worsening as any increase above the preconception baseline, and evaluated differences between focal and generalized epilepsy and between frontal lobe and other focal epilepsies.

Increased seizure activity tended to occur in women on more than one AED, according to Dr. Voinescu. In women with frontal lobe epilepsy, seizure worsening during pregnancy was most likely to begin in the second trimester.

The gap in seizure frequency between the groups narrowed in the 9-month postpartum period. Seizures were more frequent during the postpartum period, compared with baseline, in 12.12% of women with generalized epilepsy, 20.14% of women with focal epilepsies, and 20.00% of women with frontal lobe epilepsy.

Future analyses will evaluate the influence of AED type and concentration and specific timing on seizure control during pregnancy and the postpartum period, Dr. Voinescu said. Future studies should also include measures of sleep, which may be a contributory mechanism to the differences found between these epilepsy types.

Dr. Voinescu reported receiving funding from the American Brain Foundation, the American Epilepsy Society, and the Epilepsy Foundation through the Susan Spencer Clinical Research Fellowship.

[email protected]

SOURCE: Voinescu PE et al. AES 2018, Abstract 3.236.

NEW ORLEANS – Seizure frequency increased during pregnancy for 53% of women with frontal lobe epilepsy, based on a study reported by Paula E. Voinescu, MD, PhD, at the annual meeting of the American Epilepsy Society.

Jacob Remaly/MDedge News

The single center study included data on 76 pregnancies in women with focal epilepsy –17 of them in patients with frontal lobe epilepsy – and 38 pregnancies in women with generalized epilepsy. Seizures were more frequent during pregnancy, compared with baseline, in 5.5% of women with generalized epilepsy, 22.6% of women with focal epilepsies, and 53.0% of women with frontal lobe epilepsy, said Dr. Voinescu, lead author of the study and a neurologist at Brigham and Women’s Hospital in Boston.

“Frontal lobe epilepsy is known to be difficult to manage in general and often resistant to therapy, but it isn’t clear why the seizures got worse among pregnant women because the levels of medication in their blood was considered adequate. Until more research provides treatment guidance, doctors should carefully monitor their pregnant patients who have focal epilepsy to see if their seizures increase despite adequate blood levels and then adjust their medication if necessary,” she advised. “As we know from other research, seizures during pregnancy can increase the risk of distress and neurodevelopmental delays for the baby, as well as the risk of miscarriage.”

For the study, Dr. Voinescu and her colleagues analyzed prospectively collected clinical data from 99 pregnant women followed at Brigham and Women’s Hospital between 2013 and 2018.

The researchers excluded patients with abortions, seizure onset during pregnancy, poorly defined preconception seizure frequency, nonepileptic seizures, antiepileptic drug (AED) noncompliance, and pregnancies that were enrolled in other studies. The investigators documented patients’ seizure types and AED regimens and recorded seizure frequency during the 9 months before conception, during pregnancy, and 9 months postpartum. The researchers summed all seizures for each individual for each interval. They defined seizure frequency worsening as any increase above the preconception baseline, and evaluated differences between focal and generalized epilepsy and between frontal lobe and other focal epilepsies.

Increased seizure activity tended to occur in women on more than one AED, according to Dr. Voinescu. In women with frontal lobe epilepsy, seizure worsening during pregnancy was most likely to begin in the second trimester.

The gap in seizure frequency between the groups narrowed in the 9-month postpartum period. Seizures were more frequent during the postpartum period, compared with baseline, in 12.12% of women with generalized epilepsy, 20.14% of women with focal epilepsies, and 20.00% of women with frontal lobe epilepsy.

Future analyses will evaluate the influence of AED type and concentration and specific timing on seizure control during pregnancy and the postpartum period, Dr. Voinescu said. Future studies should also include measures of sleep, which may be a contributory mechanism to the differences found between these epilepsy types.

Dr. Voinescu reported receiving funding from the American Brain Foundation, the American Epilepsy Society, and the Epilepsy Foundation through the Susan Spencer Clinical Research Fellowship.

[email protected]

SOURCE: Voinescu PE et al. AES 2018, Abstract 3.236.

NEW ORLEANS – Seizure frequency increased during pregnancy for 53% of women with frontal lobe epilepsy, based on a study reported by Paula E. Voinescu, MD, PhD, at the annual meeting of the American Epilepsy Society.

Jacob Remaly/MDedge News

The single center study included data on 76 pregnancies in women with focal epilepsy –17 of them in patients with frontal lobe epilepsy – and 38 pregnancies in women with generalized epilepsy. Seizures were more frequent during pregnancy, compared with baseline, in 5.5% of women with generalized epilepsy, 22.6% of women with focal epilepsies, and 53.0% of women with frontal lobe epilepsy, said Dr. Voinescu, lead author of the study and a neurologist at Brigham and Women’s Hospital in Boston.

“Frontal lobe epilepsy is known to be difficult to manage in general and often resistant to therapy, but it isn’t clear why the seizures got worse among pregnant women because the levels of medication in their blood was considered adequate. Until more research provides treatment guidance, doctors should carefully monitor their pregnant patients who have focal epilepsy to see if their seizures increase despite adequate blood levels and then adjust their medication if necessary,” she advised. “As we know from other research, seizures during pregnancy can increase the risk of distress and neurodevelopmental delays for the baby, as well as the risk of miscarriage.”

For the study, Dr. Voinescu and her colleagues analyzed prospectively collected clinical data from 99 pregnant women followed at Brigham and Women’s Hospital between 2013 and 2018.

The researchers excluded patients with abortions, seizure onset during pregnancy, poorly defined preconception seizure frequency, nonepileptic seizures, antiepileptic drug (AED) noncompliance, and pregnancies that were enrolled in other studies. The investigators documented patients’ seizure types and AED regimens and recorded seizure frequency during the 9 months before conception, during pregnancy, and 9 months postpartum. The researchers summed all seizures for each individual for each interval. They defined seizure frequency worsening as any increase above the preconception baseline, and evaluated differences between focal and generalized epilepsy and between frontal lobe and other focal epilepsies.

Increased seizure activity tended to occur in women on more than one AED, according to Dr. Voinescu. In women with frontal lobe epilepsy, seizure worsening during pregnancy was most likely to begin in the second trimester.

The gap in seizure frequency between the groups narrowed in the 9-month postpartum period. Seizures were more frequent during the postpartum period, compared with baseline, in 12.12% of women with generalized epilepsy, 20.14% of women with focal epilepsies, and 20.00% of women with frontal lobe epilepsy.

Future analyses will evaluate the influence of AED type and concentration and specific timing on seizure control during pregnancy and the postpartum period, Dr. Voinescu said. Future studies should also include measures of sleep, which may be a contributory mechanism to the differences found between these epilepsy types.

Dr. Voinescu reported receiving funding from the American Brain Foundation, the American Epilepsy Society, and the Epilepsy Foundation through the Susan Spencer Clinical Research Fellowship.

[email protected]

SOURCE: Voinescu PE et al. AES 2018, Abstract 3.236.

NEW ORLEANS – Cannabis oil extract with a 20:1 ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) may reduce seizures in children and adults with treatment-resistant epilepsy, but about a quarter of patients develop tolerance, according to a study presented at the annual meeting of the American Epilepsy Society.

“CBD is a good option for children and adults with certain kinds of epilepsy, but as with antiepileptic drugs, it can become less effective over time, and the dose may need to be increased to manage the seizures,” said Shimrit Uliel-Sibony, MD, lead author of the study and head of the pediatric epilepsy service at Tel Aviv Sourasky Medical Center’s Dana-Dwek Children’s Hospital.

Prior studies have found that the efficacy of cannabinoids may wane when used for pain management. Efficacy also declines in animals with seizures.

To assess the tolerance rate of cannabinoids in the treatment of children and adults with epilepsy, researchers in Israel conducted a prospective review of 92 consecutive patients with treatment-resistant epilepsy. Patients were aged 1-37 years (mean age, 11.8 years) and were treated with cannabis oil extract during March 1, 2014–Dec. 31, 2017. The researchers defined tolerance as the need to increase the dose by at least 30% following a reduction in efficacy, or a more than 30% reduction in treatment response.

The patients had various forms of epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, and epilepsy caused by stroke) and used cannabis oil extract for an average of 19.8 months. Of the 84 patients included in the tolerance analysis, 21 patients (25%) developed tolerance after an average of 7.3 months (range, 1-24 months) at an average dose of 12.6 mg/kg per day. After patients with tolerance received an increased dose, 4 patients returned to their previous response levels, and 10 patients had a response that was “satisfying but less than [the] prior response level,” Dr. Uliel-Sibony and colleagues said.

About a third of patients discontinued treatment because of side effects or lack of efficacy. Side effects included sleepiness, nausea, decreased appetite, and vomiting. In addition, seizures worsened in two patients, and one patient had signs of psychosis; treatment was stopped immediately in those three patients.

The investigators had no disclosures and received no funding for this study.

[email protected]

SOURCE: Uliel-Sibony S et al., AES 2018, Abstract 2.233.

NEW ORLEANS – Cannabis oil extract with a 20:1 ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) may reduce seizures in children and adults with treatment-resistant epilepsy, but about a quarter of patients develop tolerance, according to a study presented at the annual meeting of the American Epilepsy Society.

“CBD is a good option for children and adults with certain kinds of epilepsy, but as with antiepileptic drugs, it can become less effective over time, and the dose may need to be increased to manage the seizures,” said Shimrit Uliel-Sibony, MD, lead author of the study and head of the pediatric epilepsy service at Tel Aviv Sourasky Medical Center’s Dana-Dwek Children’s Hospital.

Prior studies have found that the efficacy of cannabinoids may wane when used for pain management. Efficacy also declines in animals with seizures.

To assess the tolerance rate of cannabinoids in the treatment of children and adults with epilepsy, researchers in Israel conducted a prospective review of 92 consecutive patients with treatment-resistant epilepsy. Patients were aged 1-37 years (mean age, 11.8 years) and were treated with cannabis oil extract during March 1, 2014–Dec. 31, 2017. The researchers defined tolerance as the need to increase the dose by at least 30% following a reduction in efficacy, or a more than 30% reduction in treatment response.

The patients had various forms of epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, and epilepsy caused by stroke) and used cannabis oil extract for an average of 19.8 months. Of the 84 patients included in the tolerance analysis, 21 patients (25%) developed tolerance after an average of 7.3 months (range, 1-24 months) at an average dose of 12.6 mg/kg per day. After patients with tolerance received an increased dose, 4 patients returned to their previous response levels, and 10 patients had a response that was “satisfying but less than [the] prior response level,” Dr. Uliel-Sibony and colleagues said.

About a third of patients discontinued treatment because of side effects or lack of efficacy. Side effects included sleepiness, nausea, decreased appetite, and vomiting. In addition, seizures worsened in two patients, and one patient had signs of psychosis; treatment was stopped immediately in those three patients.

The investigators had no disclosures and received no funding for this study.

[email protected]

SOURCE: Uliel-Sibony S et al., AES 2018, Abstract 2.233.

NEW ORLEANS – Cannabis oil extract with a 20:1 ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) may reduce seizures in children and adults with treatment-resistant epilepsy, but about a quarter of patients develop tolerance, according to a study presented at the annual meeting of the American Epilepsy Society.

“CBD is a good option for children and adults with certain kinds of epilepsy, but as with antiepileptic drugs, it can become less effective over time, and the dose may need to be increased to manage the seizures,” said Shimrit Uliel-Sibony, MD, lead author of the study and head of the pediatric epilepsy service at Tel Aviv Sourasky Medical Center’s Dana-Dwek Children’s Hospital.

Prior studies have found that the efficacy of cannabinoids may wane when used for pain management. Efficacy also declines in animals with seizures.

To assess the tolerance rate of cannabinoids in the treatment of children and adults with epilepsy, researchers in Israel conducted a prospective review of 92 consecutive patients with treatment-resistant epilepsy. Patients were aged 1-37 years (mean age, 11.8 years) and were treated with cannabis oil extract during March 1, 2014–Dec. 31, 2017. The researchers defined tolerance as the need to increase the dose by at least 30% following a reduction in efficacy, or a more than 30% reduction in treatment response.

The patients had various forms of epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, and epilepsy caused by stroke) and used cannabis oil extract for an average of 19.8 months. Of the 84 patients included in the tolerance analysis, 21 patients (25%) developed tolerance after an average of 7.3 months (range, 1-24 months) at an average dose of 12.6 mg/kg per day. After patients with tolerance received an increased dose, 4 patients returned to their previous response levels, and 10 patients had a response that was “satisfying but less than [the] prior response level,” Dr. Uliel-Sibony and colleagues said.

About a third of patients discontinued treatment because of side effects or lack of efficacy. Side effects included sleepiness, nausea, decreased appetite, and vomiting. In addition, seizures worsened in two patients, and one patient had signs of psychosis; treatment was stopped immediately in those three patients.

The investigators had no disclosures and received no funding for this study.

[email protected]

SOURCE: Uliel-Sibony S et al., AES 2018, Abstract 2.233.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

[email protected]

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

[email protected]

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

NEW ORLEANS – Patients taking enzyme-inducing antiepileptic drugs (AEDs) may require a clinically meaningful increase in their vitamin D doses to achieve the same 25-hydroxyvitamin D (25[OH]D) plasma levels as patients taking nonenzyme-inducing AEDs, based on a retrospective chart review presented at the annual meeting of the American Epilepsy Society.

While patients receiving either type of AED had similar average 25(OH)D levels in the study (32.0 ng/mL in the enzyme-inducing AED group and 33.2 ng/mL in the noninducing AED group), those in the enzyme-inducing group required 1,587 U/day to meet the goal – a 409-unit increase in dose, compared with the 1,108 U/day dose taken by patients in the nonenzyme-inducing group.

“Patients taking enzyme-inducing AEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction,” said Barry E. Gidal, PharmD, professor of pharmacy and neurology at the University of Wisconsin–Madison, and his colleagues.

Researchers have suggested that enzyme-inducing AEDs may affect CYP450 isoenzymes, increase vitamin D metabolism, and reduce 25(OH)D plasma levels. “It follows … that a potential pharmacokinetic interaction could exist between enzyme-inducing AEDs and oral formulations of vitamin D used for supplementation,” the investigators said.

To test the hypothesis, Dr. Gidal and his colleagues reviewed the charts of patients with epilepsy who were on any AED regimen and were prescribed vitamin D at William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin, between January 2013 and September 2017.

The researchers grouped patients by those using enzyme-inducing AEDs and those taking noninducing AEDs. Patients who were taking AEDs in both categories were placed in the enzyme-inducing AED group. Patients with malabsorptive conditions and patients using calcitriol were excluded from the analysis.

Data included AEDs used, prescription and over-the-counter vitamin D use, 25(OH)D plasma concentration, renal function, age, gender, and ethnicity. Patients’ 25(OH)D levels were measured using a chemiluminescence immunoassay, and a minimum 25(OH)D plasma level of 30 ng/mL was the therapeutic goal.

The multivariant analysis was adjusted for potentially confounding variables including 25(OH)D concentration, over-the-counter vitamin D use, chronic kidney disease, age, gender, and ethnicity.

The analysis included 1,113 observations from 315 patients, and 263 of the observations (23.6%) were in the enzyme-inducing AED group. The enzyme-inducing group and noninducing groups were mostly male (90.5% and 91.8%, respectively) and similar in average age (65.9 and 61.4 years, respectively). Variables were evenly distributed between the groups, with the exceptions of chronic kidney disease, which was less common in the enzyme-inducing group (6.1% vs. 13.8%), and ethnicity (78.7% Caucasian in the enzyme-inducing group vs. 87.7% Caucasian in the noninducing group). The most common enzyme-inducing AED was phenytoin (50.6%), followed by carbamazepine (31.9%), phenobarbital (14.1%), oxcarbazepine (6.8%), primidone (1.9%), and eslicarbazepine (0.8%).

Dr. Gidal reported honoraria from Eisai, Sunovion, Lundbeck, and GW Pharmaceuticals.
 

[email protected]

SOURCE: Gidal BE et al. AES 2018, Abstract 1.315.

Patients with multiple sclerosis (MS) who stop taking the MS medication Gilenya (fingolimod) may experience severe disease worsening, according to a safety announcement from the Food and Drug Administration. The disease may become worse than it was before patients started the medication or while patients were taking the drug. Severe worsening is rare but can result in permanent disability, according to the FDA statement.

[email protected]

Patients with multiple sclerosis (MS) who stop taking the MS medication Gilenya (fingolimod) may experience severe disease worsening, according to a safety announcement from the Food and Drug Administration. The disease may become worse than it was before patients started the medication or while patients were taking the drug. Severe worsening is rare but can result in permanent disability, according to the FDA statement.

[email protected]

Patients with multiple sclerosis (MS) who stop taking the MS medication Gilenya (fingolimod) may experience severe disease worsening, according to a safety announcement from the Food and Drug Administration. The disease may become worse than it was before patients started the medication or while patients were taking the drug. Severe worsening is rare but can result in permanent disability, according to the FDA statement.

[email protected]