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FDA approves Epidiolex for Lennox-Gastaut syndrome and Dravet syndrome
The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.
“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.
However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”
The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.
“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.
After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.
Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.
A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.
In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.
The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.
“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.
However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”
The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.
“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.
After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.
Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.
A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.
In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.
The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.
“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.
However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”
The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.
“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.
After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.
Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.
A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.
In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.
The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
Cost of medical care for older adults with epilepsy steadily grows
An analysis of health care expenditures faced by elderly patients with epilepsy over a 12-year period in the United States found rising annual costs over time that approached a mean of $20,000, according to researchers from the Medical University of South Carolina, Charleston.
Alain Lekoubou, MD, and his colleagues estimated health care expenditures during 2003-2014 for patients aged 65 years and older with and without epilepsy by extrapolating data from the Medical Expenditure Panel Survey Household Component to more than 37 million elderly individuals in the United States. The investigators published their findings in Epilepsia.
The unadjusted mean direct health care expenditures for elderly people with epilepsy rose from $15,850 in 2003-2006 to $22,038 in 2007-2010 but dropped in 2011-2014 to $17,985. Figures for the same period for elderly people without epilepsy went from $10,214 to $10,358 to $9,965.
“The high prevalence of epilepsy and high health care expenditures in elderly patients should give priority to epilepsy in the elderly in the medical and public health communities’ agenda,” the authors wrote.
SOURCE: Lekoubou A et al. Epilepsia. 2018 June 19. doi: 10.1111/epi.14455.
An analysis of health care expenditures faced by elderly patients with epilepsy over a 12-year period in the United States found rising annual costs over time that approached a mean of $20,000, according to researchers from the Medical University of South Carolina, Charleston.
Alain Lekoubou, MD, and his colleagues estimated health care expenditures during 2003-2014 for patients aged 65 years and older with and without epilepsy by extrapolating data from the Medical Expenditure Panel Survey Household Component to more than 37 million elderly individuals in the United States. The investigators published their findings in Epilepsia.
The unadjusted mean direct health care expenditures for elderly people with epilepsy rose from $15,850 in 2003-2006 to $22,038 in 2007-2010 but dropped in 2011-2014 to $17,985. Figures for the same period for elderly people without epilepsy went from $10,214 to $10,358 to $9,965.
“The high prevalence of epilepsy and high health care expenditures in elderly patients should give priority to epilepsy in the elderly in the medical and public health communities’ agenda,” the authors wrote.
SOURCE: Lekoubou A et al. Epilepsia. 2018 June 19. doi: 10.1111/epi.14455.
An analysis of health care expenditures faced by elderly patients with epilepsy over a 12-year period in the United States found rising annual costs over time that approached a mean of $20,000, according to researchers from the Medical University of South Carolina, Charleston.
Alain Lekoubou, MD, and his colleagues estimated health care expenditures during 2003-2014 for patients aged 65 years and older with and without epilepsy by extrapolating data from the Medical Expenditure Panel Survey Household Component to more than 37 million elderly individuals in the United States. The investigators published their findings in Epilepsia.
The unadjusted mean direct health care expenditures for elderly people with epilepsy rose from $15,850 in 2003-2006 to $22,038 in 2007-2010 but dropped in 2011-2014 to $17,985. Figures for the same period for elderly people without epilepsy went from $10,214 to $10,358 to $9,965.
“The high prevalence of epilepsy and high health care expenditures in elderly patients should give priority to epilepsy in the elderly in the medical and public health communities’ agenda,” the authors wrote.
SOURCE: Lekoubou A et al. Epilepsia. 2018 June 19. doi: 10.1111/epi.14455.
FROM EPILEPSIA
Neurology Board Review: Epilepsy
Click here to read Neurology Board Review: Epilepsy
Neurology Board Review: Epilepsy is a resource developed by leading clinical educators for studying for board certification and maintenance of certification exams.
After reading the article, Click Here to Access the Board Review Questions
About the Authors
Shavonne L. Massey, MD
Clinical Instructor
Departments of Neurology and Pediatrics
Children’s Hospital of Philadelphia
University of Pennsylvania
Philadelphia, Pennsylvania
Hannah C. Glass, MDCM, MAS
Associate Professor
Departments of Neurology, Pediatrics, and
Epidemiology & Biostatistics
University of California, San Francisco
San Francisco, California
Click here to read Neurology Board Review: Epilepsy
After reading the article, Click Here to Access the Board Review Questions
Click here to read Neurology Board Review: Epilepsy
Neurology Board Review: Epilepsy is a resource developed by leading clinical educators for studying for board certification and maintenance of certification exams.
After reading the article, Click Here to Access the Board Review Questions
About the Authors
Shavonne L. Massey, MD
Clinical Instructor
Departments of Neurology and Pediatrics
Children’s Hospital of Philadelphia
University of Pennsylvania
Philadelphia, Pennsylvania
Hannah C. Glass, MDCM, MAS
Associate Professor
Departments of Neurology, Pediatrics, and
Epidemiology & Biostatistics
University of California, San Francisco
San Francisco, California
Click here to read Neurology Board Review: Epilepsy
After reading the article, Click Here to Access the Board Review Questions
Click here to read Neurology Board Review: Epilepsy
Neurology Board Review: Epilepsy is a resource developed by leading clinical educators for studying for board certification and maintenance of certification exams.
After reading the article, Click Here to Access the Board Review Questions
About the Authors
Shavonne L. Massey, MD
Clinical Instructor
Departments of Neurology and Pediatrics
Children’s Hospital of Philadelphia
University of Pennsylvania
Philadelphia, Pennsylvania
Hannah C. Glass, MDCM, MAS
Associate Professor
Departments of Neurology, Pediatrics, and
Epidemiology & Biostatistics
University of California, San Francisco
San Francisco, California
Click here to read Neurology Board Review: Epilepsy
After reading the article, Click Here to Access the Board Review Questions
Ketogenic Diet Found Effective and Well Tolerated in Children With RSE
A ketogenic diet appears to be effective for children with refractory status epilepticus (RSE) suggests a small trial that included 14 patients.
- A study conducted by the Status Epilepticus Research Group from January 2011 to December 2016 found that 71% of patients with refractory status epilepticus who received a ketogenic diet experienced seizure resolution, verified by EEG findings, within 7 days of starting the regimen.
- 79% of the children with RSE were weaned off enteral infusions of the diet within 14 days.
- Possible adverse effects from the ketogenic diet occurred in 3 of 14 patients, including gastrointestinal paresis and elevated triglyceride levels.
- The regimen produced ketosis within a median of 2 days after it was initiated.
- By 3 months, 4 patients were still seizure free and 3 had fewer seizures.
pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018;144:1-6.
A ketogenic diet appears to be effective for children with refractory status epilepticus (RSE) suggests a small trial that included 14 patients.
- A study conducted by the Status Epilepticus Research Group from January 2011 to December 2016 found that 71% of patients with refractory status epilepticus who received a ketogenic diet experienced seizure resolution, verified by EEG findings, within 7 days of starting the regimen.
- 79% of the children with RSE were weaned off enteral infusions of the diet within 14 days.
- Possible adverse effects from the ketogenic diet occurred in 3 of 14 patients, including gastrointestinal paresis and elevated triglyceride levels.
- The regimen produced ketosis within a median of 2 days after it was initiated.
- By 3 months, 4 patients were still seizure free and 3 had fewer seizures.
pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018;144:1-6.
A ketogenic diet appears to be effective for children with refractory status epilepticus (RSE) suggests a small trial that included 14 patients.
- A study conducted by the Status Epilepticus Research Group from January 2011 to December 2016 found that 71% of patients with refractory status epilepticus who received a ketogenic diet experienced seizure resolution, verified by EEG findings, within 7 days of starting the regimen.
- 79% of the children with RSE were weaned off enteral infusions of the diet within 14 days.
- Possible adverse effects from the ketogenic diet occurred in 3 of 14 patients, including gastrointestinal paresis and elevated triglyceride levels.
- The regimen produced ketosis within a median of 2 days after it was initiated.
- By 3 months, 4 patients were still seizure free and 3 had fewer seizures.
pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018;144:1-6.
Understanding Focal Cortical Dysplasia-Induced Epilepsy
The epilepsy associated with focal cortical dysplasia remains a major challenge, but early recognition of the disorder will allow clinicians to consider the possibility of resective surgery, which has been shown to eliminate seizures in some patients.
- A recent review of the medical literature found that most children with focal cortical dysplasia have intractable focal epilepsy.
- The epilepsy observed in patients with focal cortical dysplasia is related to activation of the mTOR pathway and altered receptor neurotransmission.
- The literature review discusses the epidemiology, natural history, and mechanisms that precipitate seizures in children with focal cortical dysplasia.
- Between 25% and 29% of children in a surgical series had focal cortical dysplasia.
Challenges in managing epilepsy associated with focal cortical dysplasia in children. Epilepsy Res. 2018;145:1-17.
The epilepsy associated with focal cortical dysplasia remains a major challenge, but early recognition of the disorder will allow clinicians to consider the possibility of resective surgery, which has been shown to eliminate seizures in some patients.
- A recent review of the medical literature found that most children with focal cortical dysplasia have intractable focal epilepsy.
- The epilepsy observed in patients with focal cortical dysplasia is related to activation of the mTOR pathway and altered receptor neurotransmission.
- The literature review discusses the epidemiology, natural history, and mechanisms that precipitate seizures in children with focal cortical dysplasia.
- Between 25% and 29% of children in a surgical series had focal cortical dysplasia.
Challenges in managing epilepsy associated with focal cortical dysplasia in children. Epilepsy Res. 2018;145:1-17.
The epilepsy associated with focal cortical dysplasia remains a major challenge, but early recognition of the disorder will allow clinicians to consider the possibility of resective surgery, which has been shown to eliminate seizures in some patients.
- A recent review of the medical literature found that most children with focal cortical dysplasia have intractable focal epilepsy.
- The epilepsy observed in patients with focal cortical dysplasia is related to activation of the mTOR pathway and altered receptor neurotransmission.
- The literature review discusses the epidemiology, natural history, and mechanisms that precipitate seizures in children with focal cortical dysplasia.
- Between 25% and 29% of children in a surgical series had focal cortical dysplasia.
Challenges in managing epilepsy associated with focal cortical dysplasia in children. Epilepsy Res. 2018;145:1-17.
Medication Patterns Changing for Pregnant Women with Epilepsy
Drug therapy for pregnant women with epilepsy has changed markedly in recent years according to analysis of data from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.
- MONEAD, an NIH-funded, observational, multicenter study that looked at pregnancy outcomes in mothers and their children, included women ages 14-45 years and up to 20 weeks pregnant.
- Among 351 pregnant women with epilepsy enrolled in the study, 73.8% (259) were on monotherapy and 21.9% (77) on polytherapy; 4% were not taking an antiepileptic drug.
- Lamotrigine was the most popular drug in women on monotherapy, followed by levetiracetam, carbamazepine, zonisamide, oxcarbazepine, and topiramate.
- The most common polypharmacy regimen included lamotrigine and levetiracetam.
The researchers point out that these percentages only reflect drug usage in US tertiary epilepsy centers and may not indicate usage in community practice.
MONEAD Investigator Group. Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy. Epilepsy Behav. 2018;84:10-14.
Drug therapy for pregnant women with epilepsy has changed markedly in recent years according to analysis of data from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.
- MONEAD, an NIH-funded, observational, multicenter study that looked at pregnancy outcomes in mothers and their children, included women ages 14-45 years and up to 20 weeks pregnant.
- Among 351 pregnant women with epilepsy enrolled in the study, 73.8% (259) were on monotherapy and 21.9% (77) on polytherapy; 4% were not taking an antiepileptic drug.
- Lamotrigine was the most popular drug in women on monotherapy, followed by levetiracetam, carbamazepine, zonisamide, oxcarbazepine, and topiramate.
- The most common polypharmacy regimen included lamotrigine and levetiracetam.
The researchers point out that these percentages only reflect drug usage in US tertiary epilepsy centers and may not indicate usage in community practice.
MONEAD Investigator Group. Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy. Epilepsy Behav. 2018;84:10-14.
Drug therapy for pregnant women with epilepsy has changed markedly in recent years according to analysis of data from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.
- MONEAD, an NIH-funded, observational, multicenter study that looked at pregnancy outcomes in mothers and their children, included women ages 14-45 years and up to 20 weeks pregnant.
- Among 351 pregnant women with epilepsy enrolled in the study, 73.8% (259) were on monotherapy and 21.9% (77) on polytherapy; 4% were not taking an antiepileptic drug.
- Lamotrigine was the most popular drug in women on monotherapy, followed by levetiracetam, carbamazepine, zonisamide, oxcarbazepine, and topiramate.
- The most common polypharmacy regimen included lamotrigine and levetiracetam.
The researchers point out that these percentages only reflect drug usage in US tertiary epilepsy centers and may not indicate usage in community practice.
MONEAD Investigator Group. Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy. Epilepsy Behav. 2018;84:10-14.
Vaccine-related febrile seizures have zero developmental impact
MALMO, SWEDEN – Children who experience a febrile seizure in conjunction with a vaccination have developmental outcomes comparable with those of children who have non–vaccine-related febrile seizures and healthy controls who’ve never had a febrile seizure, according to the first prospective case-control cohort study to examine the issue.
This finding has important implications for clinical practice, Lucy Deng, MD, observed at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Febrile seizures associated with a vaccine can decrease parent and provider confidence in vaccine safety,” the pediatrician noted. Based upon her study results, however, physicians now can offer a truly evidence-based message of reassurance.
“If you have a child with a vaccine-related febrile seizure, you can give the same advice to those parents as for anyone else who’s had a febrile seizure, in that there is no difference in the clinical outcomes of vaccine-proximate and non–vaccine-proximate febrile seizures. Vaccine-proximate febrile seizures are usually brief, they don’t require any antiepileptic drugs, their length of stay is usually less than a day, and developmentally at 12-24 months post initial febrile seizure, they’re exactly the same as children who’ve never had a seizure before or who’ve had a non-vaccine-related febrile seizure,” said Dr. Deng of the National Centre for Immunisation Research and Surveillance in Sydney.
The impetus for her study was straightforward: “We all know that most children with a history of febrile seizures have normal behavior, intelligence, and academic achievement and do not later develop epilepsy. What we didn’t know before is if all of these facts apply to vaccine-proximate febrile seizures,” she explained.
The clinical severity analysis portion of this prospective case-control cohort study included 1,085 children with febrile seizures seen at five Australian children’s hospitals. Sixty-eight of them had vaccine-proximate febrile seizures, for a 6.6% rate. The febrile seizures in the other 1,027 children didn’t occur within 2 weeks following a vaccination.
Measles vaccine was implicated in 56 of the 68 children with vaccine-proximate febrile seizures, or 82%. Because Australian children receive their first measles-containing vaccine at age 12 months, the average age of the cohort with vaccine-proximate febrile seizures was 13 months, significantly younger than the 20-month average for children with non–vaccine-related febrile seizures.
In a multivariate analysis adjusted for patient age, gender, and history of prior afebrile seizures, the groups with vaccine-proximate and vaccine-unrelated febrile seizures didn’t differ significantly in terms of the proportion with a hospital length of stay greater than 1 day (20% vs. 15%), ICU admission (1.5% vs. 2.3%), seizure duration of more than 15 minutes (16% vs. 12%), repeat seizures within 24 hours (9% vs. 10%), or discharge on antiepileptic medication (4.4% vs. 4.3%).
In the developmental outcomes analysis, 62 of the children with vaccine-proximate febrile seizures, 70 with vaccine-unrelated febrile seizures, and 85 healthy controls with no seizure history underwent formal assessment using the third edition of the Bayley Scales of Infant and Toddler Development 12-24 months after their initial febrile seizure. Scores adjusted for years of maternal education were closely similar in all three groups across all five test domains: cognitive, language, motor, social-emotional, and general-adaptive.
Dr. Deng reported having no financial conflicts of interest regarding the study, which was partially funded by the Australian National Centre for Immunisation Research and Surveillance.
MALMO, SWEDEN – Children who experience a febrile seizure in conjunction with a vaccination have developmental outcomes comparable with those of children who have non–vaccine-related febrile seizures and healthy controls who’ve never had a febrile seizure, according to the first prospective case-control cohort study to examine the issue.
This finding has important implications for clinical practice, Lucy Deng, MD, observed at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Febrile seizures associated with a vaccine can decrease parent and provider confidence in vaccine safety,” the pediatrician noted. Based upon her study results, however, physicians now can offer a truly evidence-based message of reassurance.
“If you have a child with a vaccine-related febrile seizure, you can give the same advice to those parents as for anyone else who’s had a febrile seizure, in that there is no difference in the clinical outcomes of vaccine-proximate and non–vaccine-proximate febrile seizures. Vaccine-proximate febrile seizures are usually brief, they don’t require any antiepileptic drugs, their length of stay is usually less than a day, and developmentally at 12-24 months post initial febrile seizure, they’re exactly the same as children who’ve never had a seizure before or who’ve had a non-vaccine-related febrile seizure,” said Dr. Deng of the National Centre for Immunisation Research and Surveillance in Sydney.
The impetus for her study was straightforward: “We all know that most children with a history of febrile seizures have normal behavior, intelligence, and academic achievement and do not later develop epilepsy. What we didn’t know before is if all of these facts apply to vaccine-proximate febrile seizures,” she explained.
The clinical severity analysis portion of this prospective case-control cohort study included 1,085 children with febrile seizures seen at five Australian children’s hospitals. Sixty-eight of them had vaccine-proximate febrile seizures, for a 6.6% rate. The febrile seizures in the other 1,027 children didn’t occur within 2 weeks following a vaccination.
Measles vaccine was implicated in 56 of the 68 children with vaccine-proximate febrile seizures, or 82%. Because Australian children receive their first measles-containing vaccine at age 12 months, the average age of the cohort with vaccine-proximate febrile seizures was 13 months, significantly younger than the 20-month average for children with non–vaccine-related febrile seizures.
In a multivariate analysis adjusted for patient age, gender, and history of prior afebrile seizures, the groups with vaccine-proximate and vaccine-unrelated febrile seizures didn’t differ significantly in terms of the proportion with a hospital length of stay greater than 1 day (20% vs. 15%), ICU admission (1.5% vs. 2.3%), seizure duration of more than 15 minutes (16% vs. 12%), repeat seizures within 24 hours (9% vs. 10%), or discharge on antiepileptic medication (4.4% vs. 4.3%).
In the developmental outcomes analysis, 62 of the children with vaccine-proximate febrile seizures, 70 with vaccine-unrelated febrile seizures, and 85 healthy controls with no seizure history underwent formal assessment using the third edition of the Bayley Scales of Infant and Toddler Development 12-24 months after their initial febrile seizure. Scores adjusted for years of maternal education were closely similar in all three groups across all five test domains: cognitive, language, motor, social-emotional, and general-adaptive.
Dr. Deng reported having no financial conflicts of interest regarding the study, which was partially funded by the Australian National Centre for Immunisation Research and Surveillance.
MALMO, SWEDEN – Children who experience a febrile seizure in conjunction with a vaccination have developmental outcomes comparable with those of children who have non–vaccine-related febrile seizures and healthy controls who’ve never had a febrile seizure, according to the first prospective case-control cohort study to examine the issue.
This finding has important implications for clinical practice, Lucy Deng, MD, observed at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Febrile seizures associated with a vaccine can decrease parent and provider confidence in vaccine safety,” the pediatrician noted. Based upon her study results, however, physicians now can offer a truly evidence-based message of reassurance.
“If you have a child with a vaccine-related febrile seizure, you can give the same advice to those parents as for anyone else who’s had a febrile seizure, in that there is no difference in the clinical outcomes of vaccine-proximate and non–vaccine-proximate febrile seizures. Vaccine-proximate febrile seizures are usually brief, they don’t require any antiepileptic drugs, their length of stay is usually less than a day, and developmentally at 12-24 months post initial febrile seizure, they’re exactly the same as children who’ve never had a seizure before or who’ve had a non-vaccine-related febrile seizure,” said Dr. Deng of the National Centre for Immunisation Research and Surveillance in Sydney.
The impetus for her study was straightforward: “We all know that most children with a history of febrile seizures have normal behavior, intelligence, and academic achievement and do not later develop epilepsy. What we didn’t know before is if all of these facts apply to vaccine-proximate febrile seizures,” she explained.
The clinical severity analysis portion of this prospective case-control cohort study included 1,085 children with febrile seizures seen at five Australian children’s hospitals. Sixty-eight of them had vaccine-proximate febrile seizures, for a 6.6% rate. The febrile seizures in the other 1,027 children didn’t occur within 2 weeks following a vaccination.
Measles vaccine was implicated in 56 of the 68 children with vaccine-proximate febrile seizures, or 82%. Because Australian children receive their first measles-containing vaccine at age 12 months, the average age of the cohort with vaccine-proximate febrile seizures was 13 months, significantly younger than the 20-month average for children with non–vaccine-related febrile seizures.
In a multivariate analysis adjusted for patient age, gender, and history of prior afebrile seizures, the groups with vaccine-proximate and vaccine-unrelated febrile seizures didn’t differ significantly in terms of the proportion with a hospital length of stay greater than 1 day (20% vs. 15%), ICU admission (1.5% vs. 2.3%), seizure duration of more than 15 minutes (16% vs. 12%), repeat seizures within 24 hours (9% vs. 10%), or discharge on antiepileptic medication (4.4% vs. 4.3%).
In the developmental outcomes analysis, 62 of the children with vaccine-proximate febrile seizures, 70 with vaccine-unrelated febrile seizures, and 85 healthy controls with no seizure history underwent formal assessment using the third edition of the Bayley Scales of Infant and Toddler Development 12-24 months after their initial febrile seizure. Scores adjusted for years of maternal education were closely similar in all three groups across all five test domains: cognitive, language, motor, social-emotional, and general-adaptive.
Dr. Deng reported having no financial conflicts of interest regarding the study, which was partially funded by the Australian National Centre for Immunisation Research and Surveillance.
REPORTING FROM ESPID 2018
Key clinical point: Parents now can confidently be reassured that vaccine-proximate febrile seizures have no long-term consequences.
Major finding: as in controls with no seizure history.
Study details: This prospective case-control study comprised 1,180 children at five Australian children’s hospitals.
Disclosures: The study was partially funded by the Australian National Centre for Immunisation Research and Surveillance. The presenter reported having no financial conflicts.
Epilepsy: Past, Present, and Future
Vijay M. Thadani,
Dr. Thadani is Professor of Neurology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. He reports no conflict of interest.
As Neurology Reviews celebrates its 25th anniversary, we take this opportunity to look back and to look ahead in the area of epilepsy care and research. Epilepsy is a disease whose earliest descriptions date back to Egypt and Mesopotamia 3,000 years ago. A modern understanding of epilepsy as an electrical disorder of the brain dates back perhaps 150 years. The last 25 years have seen considerable progress in diagnosis and treatment, but in the Western world, the prevalence of epilepsy has held steady at around 1%, and a quarter of those patients have seizures that are not controlled, in spite of appropriate therapy.
While generalized and focal seizures remain the cornerstones of classification, the most recent theoretical advance is the network concept of epilepsy. By definition, a network must have nodes and connections. In generalized forms of epilepsy, these are recognized to be diffuse groupings of neurons and the fiber tracts that connect them. They are widely distributed and conducive to the rapid and bilateral spread of electrical abnormalities throughout the brain. In focal epilepsies, the abnormal electrical activity in the network is more constrained by traditional anatomic landmarks, but this does not preclude the possibility of secondary generalization. The elucidation of such networks by intracranial EEG and fMRI studies is a major triumph of the last 25 years.
All network activities, and therefore all forms of epilepsy, are ultimately based on the electrical behavior of individual neurons. At the cellular level, the last 25 years have seen enormous progress in the understanding of normal and abnormal electrical activity, and that progress is rooted in genetics. Genetic studies, correlated with electrophysiologic ones, have identified many mutations in ion channels that are responsible for various epilepsy syndromes. Examples of this are mutations in Na+ channels that lead to Dravet syndrome and mutations in GABA receptor subunits that are responsible for juvenile myoclonic epilepsy.
The mechanistic understanding of seizures and epilepsy has also been greatly enhanced in the last three decades by structural and developmental studies closely tied to genetics. Various forms of epilepsy are caused by aberrant neurogenesis and neuronal migration, leading to dysplastic cortex that has abnormal electrical activity and connectivity. The recent elucidation of the mTOR pathway, for example, has shown us how neuronal development and migration are controlled through several genetic steps, and mutations there can lead to tuberous sclerosis and related disorders that are accompanied by epilepsy.
Treatment
From the time that epilepsy was first recognized as a disease of the brain, treatment emphasized the control of seizures and not much else. A century after the introduction of bromide, there were, by 1967, perhaps half a dozen effective drugs available, including phenobarbital, phenytoin, and carbamazepine. Between 1967 and 1993, no new drugs for epilepsy were marketed in the USA, but the next 25 years saw a dramatic improvement. The years from 1993 to 2018 saw the introduction of perhaps 15 new drugs, most recently brivaracetam. However, in spite of this huge effort, at the expense of billions of dollars, each new drug makes less than 5% of previously refractory patients seizure-free.
Surgery
The idea of treating medically refractory epilepsy by surgical removal of the epileptic focus or network goes back more than a century, but advances in the last 25 years have been based on the revolution in imaging brought about by MRI. The easy and noninvasive identification of mesial temporal sclerosis and focal cortical dysplasias has enabled thousands of patients to become seizure-free. Complete control of seizures is obtained in only 50% to 75% of patients who undergo surgery, hardly better than a century ago, but advanced imaging and electrographic techniques have made surgery possible for many patients who previously would not have been candidates.
Looking Ahead
As they say, it is difficult to make predictions, especially about the future, but one can anticipate not only the identification of more gene mutations that cause epilepsy, but their correction with CRISPR/Cas9 and related technologies. Likewise, we can anticipate new antiepileptic drugs, but whether they will be broad-spectrum blockbusters like the cannabis derivatives are thought to be, or designer molecules tailored to specific types of seizures and epilepsy remains to be seen. In tuberous sclerosis, for example, drugs like tacrolimus that inhibit the mTOR pathway not only suppress abnormal cell proliferation, but also help with seizure control. Likewise, a small minority of epilepsies, now recognized to be autoimmune, will be treated with targeted immune suppression. A major goal is the discovery of drugs that will prevent the development of epilepsy or cure it in its early stages, as opposed to merely controlling the seizures.
Imaging of epileptic foci and networks of seizure spread will continue to improve with higher field strength MRI scans. EEG, MRI, and fMRI will probably coalesce, and PET scans will play a larger role. Combined images will guide epilepsy surgeons with regard to the boundaries of resections. The nature of EEG recording will also change. Until recently, owing to the properties of available amplifiers, we have looked at electrical oscillations between 1 Hz and 70 Hz. However, much higher frequencies are increasingly recognized as important in defining the epileptogenic zone and network. Epilepsy surgery that takes high-frequency oscillations into account will optimize the removal of epileptogenic lesions and the disruption of epileptic networks, while minimizing injury to normal brain functions.
Resective surgery may itself be rendered obsolete by cerebral stimulation, now in its infancy. Implanted devices such as Neuropace have shown promise in detecting seizures and delivering a counter-shock to abort them. Biologic stimulation is also on the horizon. In animal models, transplantation of GABA-producing cells has cured epilepsy, and optogenetic techniques may soon make it possible to activate particular classes of neurons that can turn off epileptic activity.
One can also anticipate a shift in treatment away from the exclusive emphasis on seizure control. We increasingly recognize that epilepsy is much more than seizures, and that patients with epilepsy may also have depression, impaired memory, and anxiety related to their illness. In the long run, the psychosocial problems of patients with epilepsy cannot be separated from social problems as a whole. Will, for example, the new, and doubtless expensive, treatments for epilepsy be made available to all who need them, or will we be obliged to work in a two-tier system? As health care providers, we can be cautiously optimistic regarding the medical aspects of epilepsy, but we will have to think in quite unanticipated ways to ensure equitable outcomes.
Vijay M. Thadani,
Dr. Thadani is Professor of Neurology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. He reports no conflict of interest.
As Neurology Reviews celebrates its 25th anniversary, we take this opportunity to look back and to look ahead in the area of epilepsy care and research. Epilepsy is a disease whose earliest descriptions date back to Egypt and Mesopotamia 3,000 years ago. A modern understanding of epilepsy as an electrical disorder of the brain dates back perhaps 150 years. The last 25 years have seen considerable progress in diagnosis and treatment, but in the Western world, the prevalence of epilepsy has held steady at around 1%, and a quarter of those patients have seizures that are not controlled, in spite of appropriate therapy.
While generalized and focal seizures remain the cornerstones of classification, the most recent theoretical advance is the network concept of epilepsy. By definition, a network must have nodes and connections. In generalized forms of epilepsy, these are recognized to be diffuse groupings of neurons and the fiber tracts that connect them. They are widely distributed and conducive to the rapid and bilateral spread of electrical abnormalities throughout the brain. In focal epilepsies, the abnormal electrical activity in the network is more constrained by traditional anatomic landmarks, but this does not preclude the possibility of secondary generalization. The elucidation of such networks by intracranial EEG and fMRI studies is a major triumph of the last 25 years.
All network activities, and therefore all forms of epilepsy, are ultimately based on the electrical behavior of individual neurons. At the cellular level, the last 25 years have seen enormous progress in the understanding of normal and abnormal electrical activity, and that progress is rooted in genetics. Genetic studies, correlated with electrophysiologic ones, have identified many mutations in ion channels that are responsible for various epilepsy syndromes. Examples of this are mutations in Na+ channels that lead to Dravet syndrome and mutations in GABA receptor subunits that are responsible for juvenile myoclonic epilepsy.
The mechanistic understanding of seizures and epilepsy has also been greatly enhanced in the last three decades by structural and developmental studies closely tied to genetics. Various forms of epilepsy are caused by aberrant neurogenesis and neuronal migration, leading to dysplastic cortex that has abnormal electrical activity and connectivity. The recent elucidation of the mTOR pathway, for example, has shown us how neuronal development and migration are controlled through several genetic steps, and mutations there can lead to tuberous sclerosis and related disorders that are accompanied by epilepsy.
Treatment
From the time that epilepsy was first recognized as a disease of the brain, treatment emphasized the control of seizures and not much else. A century after the introduction of bromide, there were, by 1967, perhaps half a dozen effective drugs available, including phenobarbital, phenytoin, and carbamazepine. Between 1967 and 1993, no new drugs for epilepsy were marketed in the USA, but the next 25 years saw a dramatic improvement. The years from 1993 to 2018 saw the introduction of perhaps 15 new drugs, most recently brivaracetam. However, in spite of this huge effort, at the expense of billions of dollars, each new drug makes less than 5% of previously refractory patients seizure-free.
Surgery
The idea of treating medically refractory epilepsy by surgical removal of the epileptic focus or network goes back more than a century, but advances in the last 25 years have been based on the revolution in imaging brought about by MRI. The easy and noninvasive identification of mesial temporal sclerosis and focal cortical dysplasias has enabled thousands of patients to become seizure-free. Complete control of seizures is obtained in only 50% to 75% of patients who undergo surgery, hardly better than a century ago, but advanced imaging and electrographic techniques have made surgery possible for many patients who previously would not have been candidates.
Looking Ahead
As they say, it is difficult to make predictions, especially about the future, but one can anticipate not only the identification of more gene mutations that cause epilepsy, but their correction with CRISPR/Cas9 and related technologies. Likewise, we can anticipate new antiepileptic drugs, but whether they will be broad-spectrum blockbusters like the cannabis derivatives are thought to be, or designer molecules tailored to specific types of seizures and epilepsy remains to be seen. In tuberous sclerosis, for example, drugs like tacrolimus that inhibit the mTOR pathway not only suppress abnormal cell proliferation, but also help with seizure control. Likewise, a small minority of epilepsies, now recognized to be autoimmune, will be treated with targeted immune suppression. A major goal is the discovery of drugs that will prevent the development of epilepsy or cure it in its early stages, as opposed to merely controlling the seizures.
Imaging of epileptic foci and networks of seizure spread will continue to improve with higher field strength MRI scans. EEG, MRI, and fMRI will probably coalesce, and PET scans will play a larger role. Combined images will guide epilepsy surgeons with regard to the boundaries of resections. The nature of EEG recording will also change. Until recently, owing to the properties of available amplifiers, we have looked at electrical oscillations between 1 Hz and 70 Hz. However, much higher frequencies are increasingly recognized as important in defining the epileptogenic zone and network. Epilepsy surgery that takes high-frequency oscillations into account will optimize the removal of epileptogenic lesions and the disruption of epileptic networks, while minimizing injury to normal brain functions.
Resective surgery may itself be rendered obsolete by cerebral stimulation, now in its infancy. Implanted devices such as Neuropace have shown promise in detecting seizures and delivering a counter-shock to abort them. Biologic stimulation is also on the horizon. In animal models, transplantation of GABA-producing cells has cured epilepsy, and optogenetic techniques may soon make it possible to activate particular classes of neurons that can turn off epileptic activity.
One can also anticipate a shift in treatment away from the exclusive emphasis on seizure control. We increasingly recognize that epilepsy is much more than seizures, and that patients with epilepsy may also have depression, impaired memory, and anxiety related to their illness. In the long run, the psychosocial problems of patients with epilepsy cannot be separated from social problems as a whole. Will, for example, the new, and doubtless expensive, treatments for epilepsy be made available to all who need them, or will we be obliged to work in a two-tier system? As health care providers, we can be cautiously optimistic regarding the medical aspects of epilepsy, but we will have to think in quite unanticipated ways to ensure equitable outcomes.
Vijay M. Thadani,
Dr. Thadani is Professor of Neurology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. He reports no conflict of interest.
As Neurology Reviews celebrates its 25th anniversary, we take this opportunity to look back and to look ahead in the area of epilepsy care and research. Epilepsy is a disease whose earliest descriptions date back to Egypt and Mesopotamia 3,000 years ago. A modern understanding of epilepsy as an electrical disorder of the brain dates back perhaps 150 years. The last 25 years have seen considerable progress in diagnosis and treatment, but in the Western world, the prevalence of epilepsy has held steady at around 1%, and a quarter of those patients have seizures that are not controlled, in spite of appropriate therapy.
While generalized and focal seizures remain the cornerstones of classification, the most recent theoretical advance is the network concept of epilepsy. By definition, a network must have nodes and connections. In generalized forms of epilepsy, these are recognized to be diffuse groupings of neurons and the fiber tracts that connect them. They are widely distributed and conducive to the rapid and bilateral spread of electrical abnormalities throughout the brain. In focal epilepsies, the abnormal electrical activity in the network is more constrained by traditional anatomic landmarks, but this does not preclude the possibility of secondary generalization. The elucidation of such networks by intracranial EEG and fMRI studies is a major triumph of the last 25 years.
All network activities, and therefore all forms of epilepsy, are ultimately based on the electrical behavior of individual neurons. At the cellular level, the last 25 years have seen enormous progress in the understanding of normal and abnormal electrical activity, and that progress is rooted in genetics. Genetic studies, correlated with electrophysiologic ones, have identified many mutations in ion channels that are responsible for various epilepsy syndromes. Examples of this are mutations in Na+ channels that lead to Dravet syndrome and mutations in GABA receptor subunits that are responsible for juvenile myoclonic epilepsy.
The mechanistic understanding of seizures and epilepsy has also been greatly enhanced in the last three decades by structural and developmental studies closely tied to genetics. Various forms of epilepsy are caused by aberrant neurogenesis and neuronal migration, leading to dysplastic cortex that has abnormal electrical activity and connectivity. The recent elucidation of the mTOR pathway, for example, has shown us how neuronal development and migration are controlled through several genetic steps, and mutations there can lead to tuberous sclerosis and related disorders that are accompanied by epilepsy.
Treatment
From the time that epilepsy was first recognized as a disease of the brain, treatment emphasized the control of seizures and not much else. A century after the introduction of bromide, there were, by 1967, perhaps half a dozen effective drugs available, including phenobarbital, phenytoin, and carbamazepine. Between 1967 and 1993, no new drugs for epilepsy were marketed in the USA, but the next 25 years saw a dramatic improvement. The years from 1993 to 2018 saw the introduction of perhaps 15 new drugs, most recently brivaracetam. However, in spite of this huge effort, at the expense of billions of dollars, each new drug makes less than 5% of previously refractory patients seizure-free.
Surgery
The idea of treating medically refractory epilepsy by surgical removal of the epileptic focus or network goes back more than a century, but advances in the last 25 years have been based on the revolution in imaging brought about by MRI. The easy and noninvasive identification of mesial temporal sclerosis and focal cortical dysplasias has enabled thousands of patients to become seizure-free. Complete control of seizures is obtained in only 50% to 75% of patients who undergo surgery, hardly better than a century ago, but advanced imaging and electrographic techniques have made surgery possible for many patients who previously would not have been candidates.
Looking Ahead
As they say, it is difficult to make predictions, especially about the future, but one can anticipate not only the identification of more gene mutations that cause epilepsy, but their correction with CRISPR/Cas9 and related technologies. Likewise, we can anticipate new antiepileptic drugs, but whether they will be broad-spectrum blockbusters like the cannabis derivatives are thought to be, or designer molecules tailored to specific types of seizures and epilepsy remains to be seen. In tuberous sclerosis, for example, drugs like tacrolimus that inhibit the mTOR pathway not only suppress abnormal cell proliferation, but also help with seizure control. Likewise, a small minority of epilepsies, now recognized to be autoimmune, will be treated with targeted immune suppression. A major goal is the discovery of drugs that will prevent the development of epilepsy or cure it in its early stages, as opposed to merely controlling the seizures.
Imaging of epileptic foci and networks of seizure spread will continue to improve with higher field strength MRI scans. EEG, MRI, and fMRI will probably coalesce, and PET scans will play a larger role. Combined images will guide epilepsy surgeons with regard to the boundaries of resections. The nature of EEG recording will also change. Until recently, owing to the properties of available amplifiers, we have looked at electrical oscillations between 1 Hz and 70 Hz. However, much higher frequencies are increasingly recognized as important in defining the epileptogenic zone and network. Epilepsy surgery that takes high-frequency oscillations into account will optimize the removal of epileptogenic lesions and the disruption of epileptic networks, while minimizing injury to normal brain functions.
Resective surgery may itself be rendered obsolete by cerebral stimulation, now in its infancy. Implanted devices such as Neuropace have shown promise in detecting seizures and delivering a counter-shock to abort them. Biologic stimulation is also on the horizon. In animal models, transplantation of GABA-producing cells has cured epilepsy, and optogenetic techniques may soon make it possible to activate particular classes of neurons that can turn off epileptic activity.
One can also anticipate a shift in treatment away from the exclusive emphasis on seizure control. We increasingly recognize that epilepsy is much more than seizures, and that patients with epilepsy may also have depression, impaired memory, and anxiety related to their illness. In the long run, the psychosocial problems of patients with epilepsy cannot be separated from social problems as a whole. Will, for example, the new, and doubtless expensive, treatments for epilepsy be made available to all who need them, or will we be obliged to work in a two-tier system? As health care providers, we can be cautiously optimistic regarding the medical aspects of epilepsy, but we will have to think in quite unanticipated ways to ensure equitable outcomes.
Which Factors Predict Successful Epilepsy Reoperations?
LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.
“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior postoperative pathology, and fewer prior resections seem to predict better outcomes.” These results may be helpful in identifying candidates for reoperation, the investigators said.
Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful, Dr. Yardi and colleagues said. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection. Data for how outcomes vary with successive surgeries are limited, however, the researchers said.
To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic between 1995 and 2016. The investigators analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence. The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up.
The researchers analyzed the data using Kaplan–Meier survival curves and univariate and multivariate hazard modeling. The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score of greater than Class I.
Variables that correlated with better seizu
—Jake Remaly
LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.
“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior postoperative pathology, and fewer prior resections seem to predict better outcomes.” These results may be helpful in identifying candidates for reoperation, the investigators said.
Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful, Dr. Yardi and colleagues said. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection. Data for how outcomes vary with successive surgeries are limited, however, the researchers said.
To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic between 1995 and 2016. The investigators analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence. The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up.
The researchers analyzed the data using Kaplan–Meier survival curves and univariate and multivariate hazard modeling. The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score of greater than Class I.
Variables that correlated with better seizu
—Jake Remaly
LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.
“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior postoperative pathology, and fewer prior resections seem to predict better outcomes.” These results may be helpful in identifying candidates for reoperation, the investigators said.
Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful, Dr. Yardi and colleagues said. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection. Data for how outcomes vary with successive surgeries are limited, however, the researchers said.
To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic between 1995 and 2016. The investigators analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence. The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up.
The researchers analyzed the data using Kaplan–Meier survival curves and univariate and multivariate hazard modeling. The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score of greater than Class I.
Variables that correlated with better seizu
—Jake Remaly
Long-Term Perampanel Treatment Is Safe and Effective for Adolescents
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.