AES 2013

WASHINGTON – The choice of antiepileptic drugs for the treatment of pediatric convulsive status epilepticus was highly variable, and treatment timing and escalation were less than ideal in a pediatric Status Epilepticus Research Group study.

The findings suggest there is "room for improvement" in the management of this serious, life-threatening condition through more timely administration of antiepileptic drugs (AEDs) and through quicker progression from one AED to the next, Dr. Tobias Loddenkemper reported at the annual meeting of the American Epilepsy Society.

The findings represent a first step in addressing the inadequacies in the care of children with refractory convulsive status epilepticus (RCSE), and they underscore the need for parental education and ensuring that rescue medications are available for children with an epilepsy diagnosis, as well as the need for improved management in the inpatient setting, said Dr. Loddenkemper of Boston Children’s Hospital.

The analysis of RCSE episodes in 81 children aged 1 month to 21 years (mean age, 2.5 years) who were treated in the intensive care unit at any of the 11 U.S. tertiary referral hospitals that comprise the pediatric Status Epilepticus Research Group (pSERG) network showed that most episodes (79%) had onset out of the hospital. The median time to emergency medical services arrival was 15 minutes, and the median time to hospital arrival was 47 minutes. The median times to various steps of treatment far exceeded current guideline recommendations, according to Dr. Loddenkemper:

• 30 minutes for the administration of a first benzodiazepine drug by intravenous bolus dosing; guidelines call for treatment within 5 minutes.

• 69 minutes for the administration of a second drug; guidelines recommend 5-10 minutes.

• 120 minutes for the administration of a second non-benzodiazepine drug; guidelines call for 20-30 minutes.

• 180 minutes for the continuous infusion of anesthetic drugs; guidelines call for continuous infusion to begin within 30-70 minutes.

However, delays also occurred for in-hospital RCSE episodes, he said. The median times to first and second drugs for in-hospital episodes were 10 and 20 minutes, respectively.

Of the 81 patients included in the analysis, 75% were intubated and only 67% returned to baseline functioning after the RCSE episode. Four patients (4.9%) died.

"This [mortality] signifies how important this is," he said of RCSE during a press briefing at the meeting, noting that it is the most severe form of epilepsy, and that prompt and appropriate treatment is important for improving outcomes.

Of particular concern was the finding that most of the children in this study had a preexisting diagnosis of epilepsy, yet only half received a rescue medication in the outpatient setting.

"Technically, they should have had some kind of rescue medications, but they either were not given or were not prescribed," he said.

As for drug selection in this study, the most frequent choice of first benzodiazepine was lorazepam in 56% of cases, followed by diazepam in about a third of patients, and midazolam and clobazam in just a few cases each. The choice for a second benzodiazepine was most often lorazepam in 70% of cases, followed by midazolam and diazepam.

The choice of a first non-benzodiazepine drug was fosphenytoin in 52% of cases, followed by phenytoin and levetiracetam, Dr. Loddenkemper said. Phenobarbital, valproate, rufinamide, and propofol were also among the choices for first non-benzodiazepine drug. The choice of a second non-benzodiazepine drug was phenobarbital in 45% of cases, followed by levetiracetam, fosphenytoin, valproate, phenytoin, and propofol. The choice of anesthetic drug for continuous drug infusion was midazolam in 75% of cases. Other drugs used for continuous infusion included pentobarbital, propofol, and isoflurane. Pentobarbital was the first choice for second drug for infusion in 38% of cases.

The first choice of drug in each of those stages of treatment was generally within guidelines, but the high variability with respect to drug choices is concerning, he said.

All consecutive children presenting with RCSE to the ICUs in the pSERG network were included as long as they either failed at least two AEDs or required continuous infusion of an AED drug to abort their seizures.

Quicker progression from one drug to another in RCSE cases and coadministration of the first and second drugs are among strategies for improving outcomes. "Maybe we just have to treat faster," he suggested.

He also suggested that care could be improved by the use of dedicated treatment algorithms and dedicated teams of physicians who take care of patients with RCSE – much like the successful model for stroke care used at many hospitals in the United States.

Additional analysis from this study could shed more light on methods for improving outcomes. Data from an additional 46 patients are currently being analyzed, Dr. Loddenkemper said.

This study was funded by the American Epilepsy Society Infrastructure Award and the Epilepsy Foundation of America. Dr. Loddenkemper reported receiving research funding from Eisai and Lundbeck.

WASHINGTON – The choice of antiepileptic drugs for the treatment of pediatric convulsive status epilepticus was highly variable, and treatment timing and escalation were less than ideal in a pediatric Status Epilepticus Research Group study.

The findings suggest there is "room for improvement" in the management of this serious, life-threatening condition through more timely administration of antiepileptic drugs (AEDs) and through quicker progression from one AED to the next, Dr. Tobias Loddenkemper reported at the annual meeting of the American Epilepsy Society.

The findings represent a first step in addressing the inadequacies in the care of children with refractory convulsive status epilepticus (RCSE), and they underscore the need for parental education and ensuring that rescue medications are available for children with an epilepsy diagnosis, as well as the need for improved management in the inpatient setting, said Dr. Loddenkemper of Boston Children’s Hospital.

The analysis of RCSE episodes in 81 children aged 1 month to 21 years (mean age, 2.5 years) who were treated in the intensive care unit at any of the 11 U.S. tertiary referral hospitals that comprise the pediatric Status Epilepticus Research Group (pSERG) network showed that most episodes (79%) had onset out of the hospital. The median time to emergency medical services arrival was 15 minutes, and the median time to hospital arrival was 47 minutes. The median times to various steps of treatment far exceeded current guideline recommendations, according to Dr. Loddenkemper:

• 30 minutes for the administration of a first benzodiazepine drug by intravenous bolus dosing; guidelines call for treatment within 5 minutes.

• 69 minutes for the administration of a second drug; guidelines recommend 5-10 minutes.

• 120 minutes for the administration of a second non-benzodiazepine drug; guidelines call for 20-30 minutes.

• 180 minutes for the continuous infusion of anesthetic drugs; guidelines call for continuous infusion to begin within 30-70 minutes.

However, delays also occurred for in-hospital RCSE episodes, he said. The median times to first and second drugs for in-hospital episodes were 10 and 20 minutes, respectively.

Of the 81 patients included in the analysis, 75% were intubated and only 67% returned to baseline functioning after the RCSE episode. Four patients (4.9%) died.

"This [mortality] signifies how important this is," he said of RCSE during a press briefing at the meeting, noting that it is the most severe form of epilepsy, and that prompt and appropriate treatment is important for improving outcomes.

Of particular concern was the finding that most of the children in this study had a preexisting diagnosis of epilepsy, yet only half received a rescue medication in the outpatient setting.

"Technically, they should have had some kind of rescue medications, but they either were not given or were not prescribed," he said.

As for drug selection in this study, the most frequent choice of first benzodiazepine was lorazepam in 56% of cases, followed by diazepam in about a third of patients, and midazolam and clobazam in just a few cases each. The choice for a second benzodiazepine was most often lorazepam in 70% of cases, followed by midazolam and diazepam.

The choice of a first non-benzodiazepine drug was fosphenytoin in 52% of cases, followed by phenytoin and levetiracetam, Dr. Loddenkemper said. Phenobarbital, valproate, rufinamide, and propofol were also among the choices for first non-benzodiazepine drug. The choice of a second non-benzodiazepine drug was phenobarbital in 45% of cases, followed by levetiracetam, fosphenytoin, valproate, phenytoin, and propofol. The choice of anesthetic drug for continuous drug infusion was midazolam in 75% of cases. Other drugs used for continuous infusion included pentobarbital, propofol, and isoflurane. Pentobarbital was the first choice for second drug for infusion in 38% of cases.

The first choice of drug in each of those stages of treatment was generally within guidelines, but the high variability with respect to drug choices is concerning, he said.

All consecutive children presenting with RCSE to the ICUs in the pSERG network were included as long as they either failed at least two AEDs or required continuous infusion of an AED drug to abort their seizures.

Quicker progression from one drug to another in RCSE cases and coadministration of the first and second drugs are among strategies for improving outcomes. "Maybe we just have to treat faster," he suggested.

He also suggested that care could be improved by the use of dedicated treatment algorithms and dedicated teams of physicians who take care of patients with RCSE – much like the successful model for stroke care used at many hospitals in the United States.

Additional analysis from this study could shed more light on methods for improving outcomes. Data from an additional 46 patients are currently being analyzed, Dr. Loddenkemper said.

This study was funded by the American Epilepsy Society Infrastructure Award and the Epilepsy Foundation of America. Dr. Loddenkemper reported receiving research funding from Eisai and Lundbeck.

WASHINGTON – The choice of antiepileptic drugs for the treatment of pediatric convulsive status epilepticus was highly variable, and treatment timing and escalation were less than ideal in a pediatric Status Epilepticus Research Group study.

The findings suggest there is "room for improvement" in the management of this serious, life-threatening condition through more timely administration of antiepileptic drugs (AEDs) and through quicker progression from one AED to the next, Dr. Tobias Loddenkemper reported at the annual meeting of the American Epilepsy Society.

The findings represent a first step in addressing the inadequacies in the care of children with refractory convulsive status epilepticus (RCSE), and they underscore the need for parental education and ensuring that rescue medications are available for children with an epilepsy diagnosis, as well as the need for improved management in the inpatient setting, said Dr. Loddenkemper of Boston Children’s Hospital.

The analysis of RCSE episodes in 81 children aged 1 month to 21 years (mean age, 2.5 years) who were treated in the intensive care unit at any of the 11 U.S. tertiary referral hospitals that comprise the pediatric Status Epilepticus Research Group (pSERG) network showed that most episodes (79%) had onset out of the hospital. The median time to emergency medical services arrival was 15 minutes, and the median time to hospital arrival was 47 minutes. The median times to various steps of treatment far exceeded current guideline recommendations, according to Dr. Loddenkemper:

• 30 minutes for the administration of a first benzodiazepine drug by intravenous bolus dosing; guidelines call for treatment within 5 minutes.

• 69 minutes for the administration of a second drug; guidelines recommend 5-10 minutes.

• 120 minutes for the administration of a second non-benzodiazepine drug; guidelines call for 20-30 minutes.

• 180 minutes for the continuous infusion of anesthetic drugs; guidelines call for continuous infusion to begin within 30-70 minutes.

However, delays also occurred for in-hospital RCSE episodes, he said. The median times to first and second drugs for in-hospital episodes were 10 and 20 minutes, respectively.

Of the 81 patients included in the analysis, 75% were intubated and only 67% returned to baseline functioning after the RCSE episode. Four patients (4.9%) died.

"This [mortality] signifies how important this is," he said of RCSE during a press briefing at the meeting, noting that it is the most severe form of epilepsy, and that prompt and appropriate treatment is important for improving outcomes.

Of particular concern was the finding that most of the children in this study had a preexisting diagnosis of epilepsy, yet only half received a rescue medication in the outpatient setting.

"Technically, they should have had some kind of rescue medications, but they either were not given or were not prescribed," he said.

As for drug selection in this study, the most frequent choice of first benzodiazepine was lorazepam in 56% of cases, followed by diazepam in about a third of patients, and midazolam and clobazam in just a few cases each. The choice for a second benzodiazepine was most often lorazepam in 70% of cases, followed by midazolam and diazepam.

The choice of a first non-benzodiazepine drug was fosphenytoin in 52% of cases, followed by phenytoin and levetiracetam, Dr. Loddenkemper said. Phenobarbital, valproate, rufinamide, and propofol were also among the choices for first non-benzodiazepine drug. The choice of a second non-benzodiazepine drug was phenobarbital in 45% of cases, followed by levetiracetam, fosphenytoin, valproate, phenytoin, and propofol. The choice of anesthetic drug for continuous drug infusion was midazolam in 75% of cases. Other drugs used for continuous infusion included pentobarbital, propofol, and isoflurane. Pentobarbital was the first choice for second drug for infusion in 38% of cases.

The first choice of drug in each of those stages of treatment was generally within guidelines, but the high variability with respect to drug choices is concerning, he said.

All consecutive children presenting with RCSE to the ICUs in the pSERG network were included as long as they either failed at least two AEDs or required continuous infusion of an AED drug to abort their seizures.

Quicker progression from one drug to another in RCSE cases and coadministration of the first and second drugs are among strategies for improving outcomes. "Maybe we just have to treat faster," he suggested.

He also suggested that care could be improved by the use of dedicated treatment algorithms and dedicated teams of physicians who take care of patients with RCSE – much like the successful model for stroke care used at many hospitals in the United States.

Additional analysis from this study could shed more light on methods for improving outcomes. Data from an additional 46 patients are currently being analyzed, Dr. Loddenkemper said.

This study was funded by the American Epilepsy Society Infrastructure Award and the Epilepsy Foundation of America. Dr. Loddenkemper reported receiving research funding from Eisai and Lundbeck.

WASHINGTON – Resective epilepsy surgery yielded favorable long-term outcomes with respect to both seizure frequency and psychosocial factors in the majority of adult patients who participated in a recent survey.

Of 253 respondents, 82 (32%) were free of seizures at a mean of 10.6 years after surgery, and 189 (75%) had a favorable outcome, defined as Engel’s Class I or II surgery outcome, Dr. Marianna V. Spanaki-Varelas reported in a poster at the annual meeting of the American Epilepsy Society.

Overall, more than half (51%) of the patients were driving after surgery, compared with 35% before surgery, Dr. Spanaki-Varelas of Henry Ford Comprehensive Epilepsy Program, Detroit.

Respondents were less likely currently to be working full time when surveyed vs. prior to surgery (23% vs. 42%), but employment was greater in the 85% of patients who underwent temporal vs. extratemporal resection (45% vs. 26%).

Also, more patients were using antidepressants after surgery, compared with before surgery (30% vs. 22%).

Among the patients with favorable outcomes, 65% were driving after surgery (compared with 11% of those without a favorable outcome), 28% were currently employed, (compared with 8% of those without favorable outcomes), and only 24% were taking antidepressants (compared with 47% of those without a favorable outcome).

Perhaps most notable was that regardless of surgery site, 92% of respondents considered epilepsy surgery worthwhile, including 98% of those with a favorable outcome and 74% of those without a favorable outcome.

Even in patients without a favorable outcome, seizure frequency was often reduced and patients were satisfied, she explained, noting that the findings reinforce the importance of quality of life – and the ability of surgery to enhance quality of life, and they suggest that referral for surgery should be considered earlier in the course of treatment.

The respondents had a mean age of 46 years at the time of the survey, a mean age of nearly 16 years at epilepsy diagnosis, and a mean age of 35 years at the time of surgery, which took place at the Henry Ford Epilepsy Program between 1993 and 2011. Patient records were retrospectively reviewed, and the patients were surveyed between May 2012 and January 2013.

Nearly a third (30%) had follow-up of at least 20 years, Dr. Spanaki-Varelas noted.

It is concerning that potentially life-changing surgery is being delayed nearly 20 years for many patients, she said, noting that part of the reason for delay is the common misconception that the more medications a patient tries, the better their outcome will be. This delays evaluations for surgical intervention. Also, surveys suggest that many physicians don’t refer patients for surgical evaluation because they don’t feel confident regarding their knowledge of the risks and benefits of surgery.

These findings underscore the need for better patient education, which may improve self-referral rates, she said.

WASHINGTON – Resective epilepsy surgery yielded favorable long-term outcomes with respect to both seizure frequency and psychosocial factors in the majority of adult patients who participated in a recent survey.

Of 253 respondents, 82 (32%) were free of seizures at a mean of 10.6 years after surgery, and 189 (75%) had a favorable outcome, defined as Engel’s Class I or II surgery outcome, Dr. Marianna V. Spanaki-Varelas reported in a poster at the annual meeting of the American Epilepsy Society.

Overall, more than half (51%) of the patients were driving after surgery, compared with 35% before surgery, Dr. Spanaki-Varelas of Henry Ford Comprehensive Epilepsy Program, Detroit.

Respondents were less likely currently to be working full time when surveyed vs. prior to surgery (23% vs. 42%), but employment was greater in the 85% of patients who underwent temporal vs. extratemporal resection (45% vs. 26%).

Also, more patients were using antidepressants after surgery, compared with before surgery (30% vs. 22%).

Among the patients with favorable outcomes, 65% were driving after surgery (compared with 11% of those without a favorable outcome), 28% were currently employed, (compared with 8% of those without favorable outcomes), and only 24% were taking antidepressants (compared with 47% of those without a favorable outcome).

Perhaps most notable was that regardless of surgery site, 92% of respondents considered epilepsy surgery worthwhile, including 98% of those with a favorable outcome and 74% of those without a favorable outcome.

Even in patients without a favorable outcome, seizure frequency was often reduced and patients were satisfied, she explained, noting that the findings reinforce the importance of quality of life – and the ability of surgery to enhance quality of life, and they suggest that referral for surgery should be considered earlier in the course of treatment.

The respondents had a mean age of 46 years at the time of the survey, a mean age of nearly 16 years at epilepsy diagnosis, and a mean age of 35 years at the time of surgery, which took place at the Henry Ford Epilepsy Program between 1993 and 2011. Patient records were retrospectively reviewed, and the patients were surveyed between May 2012 and January 2013.

Nearly a third (30%) had follow-up of at least 20 years, Dr. Spanaki-Varelas noted.

It is concerning that potentially life-changing surgery is being delayed nearly 20 years for many patients, she said, noting that part of the reason for delay is the common misconception that the more medications a patient tries, the better their outcome will be. This delays evaluations for surgical intervention. Also, surveys suggest that many physicians don’t refer patients for surgical evaluation because they don’t feel confident regarding their knowledge of the risks and benefits of surgery.

These findings underscore the need for better patient education, which may improve self-referral rates, she said.

WASHINGTON – Resective epilepsy surgery yielded favorable long-term outcomes with respect to both seizure frequency and psychosocial factors in the majority of adult patients who participated in a recent survey.

Of 253 respondents, 82 (32%) were free of seizures at a mean of 10.6 years after surgery, and 189 (75%) had a favorable outcome, defined as Engel’s Class I or II surgery outcome, Dr. Marianna V. Spanaki-Varelas reported in a poster at the annual meeting of the American Epilepsy Society.

Overall, more than half (51%) of the patients were driving after surgery, compared with 35% before surgery, Dr. Spanaki-Varelas of Henry Ford Comprehensive Epilepsy Program, Detroit.

Respondents were less likely currently to be working full time when surveyed vs. prior to surgery (23% vs. 42%), but employment was greater in the 85% of patients who underwent temporal vs. extratemporal resection (45% vs. 26%).

Also, more patients were using antidepressants after surgery, compared with before surgery (30% vs. 22%).

Among the patients with favorable outcomes, 65% were driving after surgery (compared with 11% of those without a favorable outcome), 28% were currently employed, (compared with 8% of those without favorable outcomes), and only 24% were taking antidepressants (compared with 47% of those without a favorable outcome).

Perhaps most notable was that regardless of surgery site, 92% of respondents considered epilepsy surgery worthwhile, including 98% of those with a favorable outcome and 74% of those without a favorable outcome.

Even in patients without a favorable outcome, seizure frequency was often reduced and patients were satisfied, she explained, noting that the findings reinforce the importance of quality of life – and the ability of surgery to enhance quality of life, and they suggest that referral for surgery should be considered earlier in the course of treatment.

The respondents had a mean age of 46 years at the time of the survey, a mean age of nearly 16 years at epilepsy diagnosis, and a mean age of 35 years at the time of surgery, which took place at the Henry Ford Epilepsy Program between 1993 and 2011. Patient records were retrospectively reviewed, and the patients were surveyed between May 2012 and January 2013.

Nearly a third (30%) had follow-up of at least 20 years, Dr. Spanaki-Varelas noted.

It is concerning that potentially life-changing surgery is being delayed nearly 20 years for many patients, she said, noting that part of the reason for delay is the common misconception that the more medications a patient tries, the better their outcome will be. This delays evaluations for surgical intervention. Also, surveys suggest that many physicians don’t refer patients for surgical evaluation because they don’t feel confident regarding their knowledge of the risks and benefits of surgery.

These findings underscore the need for better patient education, which may improve self-referral rates, she said.

WASHINGTON – Recently identified genes associated with severe epilepsies have shed some light on biological pathways involved in epileptogenesis, which could eventually lead to targeted treatments, Gemma Carvill, Ph.D., said at the annual meeting of the American Epilepsy Society.

The findings from a study of over 600 patients with epilepsy, which include the identification of several genes in patients linked to epileptic encephalopathies (EEs), also have diagnostic implications, according to Dr. Carvill, a postdoctoral fellow in the department of pediatrics and genetic medicine at the University of Washington, Seattle, and the lead author of the study.

Elizabeth Mechcatie/Frontline Medical News

EEs, the most severe types of epilepsy, primarily affect children and typically involve regression after normal development normally. They tend to be refractory to treatment.

This study is an expansion of a study she and her associates reported earlier this year (Nat. Genet. 2013;45:825-30), which involved the sequencing of 19 known EE genes and 46 candidate genes in 500 patients with EEs. They made a genetic diagnosis in 10% of these patients, identifying six new genes linked to EE, including two – CHD2 and SYNGAP1 – that accounted for about 1% of EE cases each.

Mutations in CHD2 do not directly affect the regulation of neurotransmitters at the synapse but affect the structure of DNA. "We think that changes the expression of genes downstream and affects the development of the human brain," which is a hypothesis she and her associates are researching, Dr. Carvill noted during a press briefing at the meeting.

"The vast majority of EEs are refractory to current treatment, so by identifying this new gene we’re identifying new biology, and we’re exploring new pathways and potentially new ways in which we can think about treating this disorder," she said.

This finding also may be important for the "broader spectrum of neurodevelopment disorders," Dr. Carvill said, noting that they have started screening patients with other types of neurodevelopment disorders for CHD2 mutations.

The expanded study included the addition of more patients with EE as well as patients with intellectual disabilities and genetic generalized epilepsy. Dr. Carvill and her colleagues also tested more target genes, including other genes linked to EE and genes associated with neurodevelopmental disorders.

Among the preliminary results of the expanded study are the identification of specific genes associated with "discrete phenotypes," she reported. These include mutations in the GRIN2A gene, which cause epilepsy aphasia syndromes. The investigators identified four families with mutations in the GRIN2A gene, which were associated with epilepsy aphasia, a type of epilepsy in which children tend to develop normally but then lose speech and have a certain EEG pattern during sleep, Dr. Carvill said.

This is a very specific phenotype and the finding has important diagnostic implications, she added, noting that a clinician who sees this particular phenotype in a patient can obtain a screening test for this gene.

They also identified patients with mutations in the GABRA1 (gamma-aminobutyric acid [GABA] A receptor, alpha 1) gene, which cause Dravet syndrome (also known as severe myoclonic epilepsy of infancy).

The study was funded by the National Institutes of Health. Dr. Carvill had no disclosures.

[email protected]

WASHINGTON – Recently identified genes associated with severe epilepsies have shed some light on biological pathways involved in epileptogenesis, which could eventually lead to targeted treatments, Gemma Carvill, Ph.D., said at the annual meeting of the American Epilepsy Society.

The findings from a study of over 600 patients with epilepsy, which include the identification of several genes in patients linked to epileptic encephalopathies (EEs), also have diagnostic implications, according to Dr. Carvill, a postdoctoral fellow in the department of pediatrics and genetic medicine at the University of Washington, Seattle, and the lead author of the study.

Elizabeth Mechcatie/Frontline Medical News

EEs, the most severe types of epilepsy, primarily affect children and typically involve regression after normal development normally. They tend to be refractory to treatment.

This study is an expansion of a study she and her associates reported earlier this year (Nat. Genet. 2013;45:825-30), which involved the sequencing of 19 known EE genes and 46 candidate genes in 500 patients with EEs. They made a genetic diagnosis in 10% of these patients, identifying six new genes linked to EE, including two – CHD2 and SYNGAP1 – that accounted for about 1% of EE cases each.

Mutations in CHD2 do not directly affect the regulation of neurotransmitters at the synapse but affect the structure of DNA. "We think that changes the expression of genes downstream and affects the development of the human brain," which is a hypothesis she and her associates are researching, Dr. Carvill noted during a press briefing at the meeting.

"The vast majority of EEs are refractory to current treatment, so by identifying this new gene we’re identifying new biology, and we’re exploring new pathways and potentially new ways in which we can think about treating this disorder," she said.

This finding also may be important for the "broader spectrum of neurodevelopment disorders," Dr. Carvill said, noting that they have started screening patients with other types of neurodevelopment disorders for CHD2 mutations.

The expanded study included the addition of more patients with EE as well as patients with intellectual disabilities and genetic generalized epilepsy. Dr. Carvill and her colleagues also tested more target genes, including other genes linked to EE and genes associated with neurodevelopmental disorders.

Among the preliminary results of the expanded study are the identification of specific genes associated with "discrete phenotypes," she reported. These include mutations in the GRIN2A gene, which cause epilepsy aphasia syndromes. The investigators identified four families with mutations in the GRIN2A gene, which were associated with epilepsy aphasia, a type of epilepsy in which children tend to develop normally but then lose speech and have a certain EEG pattern during sleep, Dr. Carvill said.

This is a very specific phenotype and the finding has important diagnostic implications, she added, noting that a clinician who sees this particular phenotype in a patient can obtain a screening test for this gene.

They also identified patients with mutations in the GABRA1 (gamma-aminobutyric acid [GABA] A receptor, alpha 1) gene, which cause Dravet syndrome (also known as severe myoclonic epilepsy of infancy).

The study was funded by the National Institutes of Health. Dr. Carvill had no disclosures.

[email protected]

WASHINGTON – Recently identified genes associated with severe epilepsies have shed some light on biological pathways involved in epileptogenesis, which could eventually lead to targeted treatments, Gemma Carvill, Ph.D., said at the annual meeting of the American Epilepsy Society.

The findings from a study of over 600 patients with epilepsy, which include the identification of several genes in patients linked to epileptic encephalopathies (EEs), also have diagnostic implications, according to Dr. Carvill, a postdoctoral fellow in the department of pediatrics and genetic medicine at the University of Washington, Seattle, and the lead author of the study.

Elizabeth Mechcatie/Frontline Medical News

EEs, the most severe types of epilepsy, primarily affect children and typically involve regression after normal development normally. They tend to be refractory to treatment.

This study is an expansion of a study she and her associates reported earlier this year (Nat. Genet. 2013;45:825-30), which involved the sequencing of 19 known EE genes and 46 candidate genes in 500 patients with EEs. They made a genetic diagnosis in 10% of these patients, identifying six new genes linked to EE, including two – CHD2 and SYNGAP1 – that accounted for about 1% of EE cases each.

Mutations in CHD2 do not directly affect the regulation of neurotransmitters at the synapse but affect the structure of DNA. "We think that changes the expression of genes downstream and affects the development of the human brain," which is a hypothesis she and her associates are researching, Dr. Carvill noted during a press briefing at the meeting.

"The vast majority of EEs are refractory to current treatment, so by identifying this new gene we’re identifying new biology, and we’re exploring new pathways and potentially new ways in which we can think about treating this disorder," she said.

This finding also may be important for the "broader spectrum of neurodevelopment disorders," Dr. Carvill said, noting that they have started screening patients with other types of neurodevelopment disorders for CHD2 mutations.

The expanded study included the addition of more patients with EE as well as patients with intellectual disabilities and genetic generalized epilepsy. Dr. Carvill and her colleagues also tested more target genes, including other genes linked to EE and genes associated with neurodevelopmental disorders.

Among the preliminary results of the expanded study are the identification of specific genes associated with "discrete phenotypes," she reported. These include mutations in the GRIN2A gene, which cause epilepsy aphasia syndromes. The investigators identified four families with mutations in the GRIN2A gene, which were associated with epilepsy aphasia, a type of epilepsy in which children tend to develop normally but then lose speech and have a certain EEG pattern during sleep, Dr. Carvill said.

This is a very specific phenotype and the finding has important diagnostic implications, she added, noting that a clinician who sees this particular phenotype in a patient can obtain a screening test for this gene.

They also identified patients with mutations in the GABRA1 (gamma-aminobutyric acid [GABA] A receptor, alpha 1) gene, which cause Dravet syndrome (also known as severe myoclonic epilepsy of infancy).

The study was funded by the National Institutes of Health. Dr. Carvill had no disclosures.

[email protected]

WASHINGTON – Rapidly withdrawing antiepileptic medications in patients with epilepsy before being evaluated with video-electroencephalographic monitoring was safe, with no deaths or serious morbidity, in a prospective study, Dr. Syed Rizvi reported at the annual meeting of the American Epilepsy Society.

Video-electroencephalographic monitoring (VEM) also reliably helped to plan treatment, including surgery, and outcomes were "excellent," Dr. Rizvi of the department of neurology at the University of Saskatchewan, Saskatoon, Canada, said at a press briefing during the meeting.

The literature on whether it is safe and effective to rapidly withdraw antiepileptic drugs during VEM is sparse, he noted.

In 158 patients who had been admitted for VEM to the university’s epilepsy monitoring unit during a 5-year period, antiepileptic drugs (AEDs), except for phenobarbital, were rapidly withdrawn in patients who had no history of status epilepticus. The patients also underwent supervised overnight sleep deprivation. Rapid withdrawal was performed by titrating AEDs to half-dose on admission and then discontinuing them at 24 hours. In cases in which there was a history of status epilepticus or in patients taking phenobarbital or high doses of benzodiazepines, AEDs were tapered by 25% of the initial dose and ultimately discontinued.

The patients had had a mean of almost 11 seizures in the month before VEM, and 70% of patients were on three or more AEDs. Their mean age was 37 years, and they had had epilepsy for a mean of 16 years (mean age of onset was 20.5 years).

About 5% of patients had complications, which were mostly minor, including musculoskeletal pain secondary to seizure activity. During the month after testing, four (2.5%) patients were admitted to the emergency department for seizure clustering, but none were admitted to the intensive care unit. There were no deaths.

About 90% of the patients were diagnosed on the basis of VEM results, "a high diagnostic yield," Dr. Rizvi said. Habitual seizures were detected in 107 patients and psychogenic nonepileptic seizures were diagnosed in 36 patients; in 15 patients (9.5%), no events were recorded during VEM.

Almost 33% – 52 of the 158 – patients had epilepsy surgery, based on the results. Of those patients who had surgery, almost 90% achieved an excellent outcome (Engel Class I or II status) at 24 months, he said, noting that these patients were "virtually seizure free" or had nondebilitating seizures.

Video-EEG monitoring was "highly effective. It’s a useful adjunct in decision making. It can help in deciding which patients are suitable for surgery" in the "appropriate context," with supervision by a team of epileptologists, nurses, and EEG technologists, Dr. Rizvi said during the press briefing. He said that he and his coinvestigators hope to expand the study to include elderly and pediatric patients.

The study was not funded. Dr. Rizvi, a senior neurology resident at the university, had no disclosures.

[email protected]

WASHINGTON – Rapidly withdrawing antiepileptic medications in patients with epilepsy before being evaluated with video-electroencephalographic monitoring was safe, with no deaths or serious morbidity, in a prospective study, Dr. Syed Rizvi reported at the annual meeting of the American Epilepsy Society.

Video-electroencephalographic monitoring (VEM) also reliably helped to plan treatment, including surgery, and outcomes were "excellent," Dr. Rizvi of the department of neurology at the University of Saskatchewan, Saskatoon, Canada, said at a press briefing during the meeting.

The literature on whether it is safe and effective to rapidly withdraw antiepileptic drugs during VEM is sparse, he noted.

In 158 patients who had been admitted for VEM to the university’s epilepsy monitoring unit during a 5-year period, antiepileptic drugs (AEDs), except for phenobarbital, were rapidly withdrawn in patients who had no history of status epilepticus. The patients also underwent supervised overnight sleep deprivation. Rapid withdrawal was performed by titrating AEDs to half-dose on admission and then discontinuing them at 24 hours. In cases in which there was a history of status epilepticus or in patients taking phenobarbital or high doses of benzodiazepines, AEDs were tapered by 25% of the initial dose and ultimately discontinued.

The patients had had a mean of almost 11 seizures in the month before VEM, and 70% of patients were on three or more AEDs. Their mean age was 37 years, and they had had epilepsy for a mean of 16 years (mean age of onset was 20.5 years).

About 5% of patients had complications, which were mostly minor, including musculoskeletal pain secondary to seizure activity. During the month after testing, four (2.5%) patients were admitted to the emergency department for seizure clustering, but none were admitted to the intensive care unit. There were no deaths.

About 90% of the patients were diagnosed on the basis of VEM results, "a high diagnostic yield," Dr. Rizvi said. Habitual seizures were detected in 107 patients and psychogenic nonepileptic seizures were diagnosed in 36 patients; in 15 patients (9.5%), no events were recorded during VEM.

Almost 33% – 52 of the 158 – patients had epilepsy surgery, based on the results. Of those patients who had surgery, almost 90% achieved an excellent outcome (Engel Class I or II status) at 24 months, he said, noting that these patients were "virtually seizure free" or had nondebilitating seizures.

Video-EEG monitoring was "highly effective. It’s a useful adjunct in decision making. It can help in deciding which patients are suitable for surgery" in the "appropriate context," with supervision by a team of epileptologists, nurses, and EEG technologists, Dr. Rizvi said during the press briefing. He said that he and his coinvestigators hope to expand the study to include elderly and pediatric patients.

The study was not funded. Dr. Rizvi, a senior neurology resident at the university, had no disclosures.

[email protected]

WASHINGTON – Rapidly withdrawing antiepileptic medications in patients with epilepsy before being evaluated with video-electroencephalographic monitoring was safe, with no deaths or serious morbidity, in a prospective study, Dr. Syed Rizvi reported at the annual meeting of the American Epilepsy Society.

Video-electroencephalographic monitoring (VEM) also reliably helped to plan treatment, including surgery, and outcomes were "excellent," Dr. Rizvi of the department of neurology at the University of Saskatchewan, Saskatoon, Canada, said at a press briefing during the meeting.

The literature on whether it is safe and effective to rapidly withdraw antiepileptic drugs during VEM is sparse, he noted.

In 158 patients who had been admitted for VEM to the university’s epilepsy monitoring unit during a 5-year period, antiepileptic drugs (AEDs), except for phenobarbital, were rapidly withdrawn in patients who had no history of status epilepticus. The patients also underwent supervised overnight sleep deprivation. Rapid withdrawal was performed by titrating AEDs to half-dose on admission and then discontinuing them at 24 hours. In cases in which there was a history of status epilepticus or in patients taking phenobarbital or high doses of benzodiazepines, AEDs were tapered by 25% of the initial dose and ultimately discontinued.

The patients had had a mean of almost 11 seizures in the month before VEM, and 70% of patients were on three or more AEDs. Their mean age was 37 years, and they had had epilepsy for a mean of 16 years (mean age of onset was 20.5 years).

About 5% of patients had complications, which were mostly minor, including musculoskeletal pain secondary to seizure activity. During the month after testing, four (2.5%) patients were admitted to the emergency department for seizure clustering, but none were admitted to the intensive care unit. There were no deaths.

About 90% of the patients were diagnosed on the basis of VEM results, "a high diagnostic yield," Dr. Rizvi said. Habitual seizures were detected in 107 patients and psychogenic nonepileptic seizures were diagnosed in 36 patients; in 15 patients (9.5%), no events were recorded during VEM.

Almost 33% – 52 of the 158 – patients had epilepsy surgery, based on the results. Of those patients who had surgery, almost 90% achieved an excellent outcome (Engel Class I or II status) at 24 months, he said, noting that these patients were "virtually seizure free" or had nondebilitating seizures.

Video-EEG monitoring was "highly effective. It’s a useful adjunct in decision making. It can help in deciding which patients are suitable for surgery" in the "appropriate context," with supervision by a team of epileptologists, nurses, and EEG technologists, Dr. Rizvi said during the press briefing. He said that he and his coinvestigators hope to expand the study to include elderly and pediatric patients.

The study was not funded. Dr. Rizvi, a senior neurology resident at the university, had no disclosures.

[email protected]