Literature Monitor

Adult tertiary epilepsy centers often lack the resources to manage young adult patients who are making the transition from pediatric centers, according to a study published in the October issue of Epilepsia.

“These transitioned patients require more resources and services than other young patients with epilepsy” who are receiving care in the community, said Felippe Borlot, MD, and colleagues. In addition, adult neurologists, “even those specialized in epilepsy, may not feel that they are adequately prepared to diagnose and treat part of this complex population.”

For the retrospective study, Dr. Borlot, an epilepsy fellow at the University of Toronto, and his colleagues reviewed the records of all young adults, ages 18 through 25, with childhood-onset epilepsy seen during a six-year period at a single adult tertiary epilepsy care site. The researchers reviewed patient demographic data, etiologies, and treatment regimens before sorting patients into two groups.

The first group of 170 patients had been referred from a pediatric epilepsy tertiary care center. The second group of 132 patients was age-matched with that group and consisted of people referred by community physicians, including pediatric neurologists, to the adult tertiary center. The mean age for the first group was 21.9, and the mean age for the second group was 23.2.

The first group had earlier seizure onset, longer epilepsy duration, more symptomatic etiologies, epileptic encephalopathy, and cognitive delay. The first group also required more care from other specialists, as well as polytherapy, epilepsy surgery, a ketogenic diet, and a vagus nerve stimulator. Patients from tertiary centers present more complex health care needs and require more resources than age-matched patients from the community, said Dr. Borlot and his coinvestigators.

The researchers also surveyed 86 adult neurologists and 29 pediatric neurologists. On a scale of 1 (not comfortable at all) to 5 (very comfortable), the neurologists were asked to rate their comfort level in dealing with several types of epilepsy. The survey also asked how the neurologists felt about treating attendant issues such as intellectual disabilities and autistic features.

The survey results, although not validated, showed that adult neurologists had less confidence diagnosing and treating more severe forms of childhood-onset epilepsies, as well as epilepsy associated with cognitive delay.

The study lacked data validating a successful transition from pediatric to adult care. Also, it did not include patients who were not assessed in the 12 months before the study, meaning that it was not possible to determine the percentage of patients lost to follow-up. Nevertheless, the investigators concluded that the data were useful because no previous evaluation of transition of care in the epileptic setting was available.

Dr. Borlot and his coauthors concluded that transition of care for patients with epilepsy may be enhanced by efforts to “make childhood-onset epilepsies part of adult neurologists’ training and certification requirements.”

—Whitney McKnight

Adult tertiary epilepsy centers often lack the resources to manage young adult patients who are making the transition from pediatric centers, according to a study published in the October issue of Epilepsia.

“These transitioned patients require more resources and services than other young patients with epilepsy” who are receiving care in the community, said Felippe Borlot, MD, and colleagues. In addition, adult neurologists, “even those specialized in epilepsy, may not feel that they are adequately prepared to diagnose and treat part of this complex population.”

For the retrospective study, Dr. Borlot, an epilepsy fellow at the University of Toronto, and his colleagues reviewed the records of all young adults, ages 18 through 25, with childhood-onset epilepsy seen during a six-year period at a single adult tertiary epilepsy care site. The researchers reviewed patient demographic data, etiologies, and treatment regimens before sorting patients into two groups.

The first group of 170 patients had been referred from a pediatric epilepsy tertiary care center. The second group of 132 patients was age-matched with that group and consisted of people referred by community physicians, including pediatric neurologists, to the adult tertiary center. The mean age for the first group was 21.9, and the mean age for the second group was 23.2.

The first group had earlier seizure onset, longer epilepsy duration, more symptomatic etiologies, epileptic encephalopathy, and cognitive delay. The first group also required more care from other specialists, as well as polytherapy, epilepsy surgery, a ketogenic diet, and a vagus nerve stimulator. Patients from tertiary centers present more complex health care needs and require more resources than age-matched patients from the community, said Dr. Borlot and his coinvestigators.

The researchers also surveyed 86 adult neurologists and 29 pediatric neurologists. On a scale of 1 (not comfortable at all) to 5 (very comfortable), the neurologists were asked to rate their comfort level in dealing with several types of epilepsy. The survey also asked how the neurologists felt about treating attendant issues such as intellectual disabilities and autistic features.

The survey results, although not validated, showed that adult neurologists had less confidence diagnosing and treating more severe forms of childhood-onset epilepsies, as well as epilepsy associated with cognitive delay.

The study lacked data validating a successful transition from pediatric to adult care. Also, it did not include patients who were not assessed in the 12 months before the study, meaning that it was not possible to determine the percentage of patients lost to follow-up. Nevertheless, the investigators concluded that the data were useful because no previous evaluation of transition of care in the epileptic setting was available.

Dr. Borlot and his coauthors concluded that transition of care for patients with epilepsy may be enhanced by efforts to “make childhood-onset epilepsies part of adult neurologists’ training and certification requirements.”

—Whitney McKnight

Adult tertiary epilepsy centers often lack the resources to manage young adult patients who are making the transition from pediatric centers, according to a study published in the October issue of Epilepsia.

“These transitioned patients require more resources and services than other young patients with epilepsy” who are receiving care in the community, said Felippe Borlot, MD, and colleagues. In addition, adult neurologists, “even those specialized in epilepsy, may not feel that they are adequately prepared to diagnose and treat part of this complex population.”

For the retrospective study, Dr. Borlot, an epilepsy fellow at the University of Toronto, and his colleagues reviewed the records of all young adults, ages 18 through 25, with childhood-onset epilepsy seen during a six-year period at a single adult tertiary epilepsy care site. The researchers reviewed patient demographic data, etiologies, and treatment regimens before sorting patients into two groups.

The first group of 170 patients had been referred from a pediatric epilepsy tertiary care center. The second group of 132 patients was age-matched with that group and consisted of people referred by community physicians, including pediatric neurologists, to the adult tertiary center. The mean age for the first group was 21.9, and the mean age for the second group was 23.2.

The first group had earlier seizure onset, longer epilepsy duration, more symptomatic etiologies, epileptic encephalopathy, and cognitive delay. The first group also required more care from other specialists, as well as polytherapy, epilepsy surgery, a ketogenic diet, and a vagus nerve stimulator. Patients from tertiary centers present more complex health care needs and require more resources than age-matched patients from the community, said Dr. Borlot and his coinvestigators.

The researchers also surveyed 86 adult neurologists and 29 pediatric neurologists. On a scale of 1 (not comfortable at all) to 5 (very comfortable), the neurologists were asked to rate their comfort level in dealing with several types of epilepsy. The survey also asked how the neurologists felt about treating attendant issues such as intellectual disabilities and autistic features.

The survey results, although not validated, showed that adult neurologists had less confidence diagnosing and treating more severe forms of childhood-onset epilepsies, as well as epilepsy associated with cognitive delay.

The study lacked data validating a successful transition from pediatric to adult care. Also, it did not include patients who were not assessed in the 12 months before the study, meaning that it was not possible to determine the percentage of patients lost to follow-up. Nevertheless, the investigators concluded that the data were useful because no previous evaluation of transition of care in the epileptic setting was available.

Dr. Borlot and his coauthors concluded that transition of care for patients with epilepsy may be enhanced by efforts to “make childhood-onset epilepsies part of adult neurologists’ training and certification requirements.”

—Whitney McKnight

Adjunctive vagus nerve stimulation (VNS) therapy may significantly reduce seizure activity for more than one-third of children with drug-resistant epilepsy, according to a large, retrospective, multicenter study, which was published in the October issue of Epilepsia.

Iren Orosz, MD, a pediatrician at the Medical University of Lübeck, Germany, and her colleagues at 11 medical centers across Europe found that 130 (37.6%) of 346 patients with drug-resistant epilepsy had at least a 50% reduction in seizures 12 months after being implanted with a VNS device. This group of patients included 19 (5.5%) who became seizure free and 111 (32.1%) who achieved a 50% to 99% reduction in seizure frequency. A total of 59 patients (17.1%) had a 25% to 49% reduction in seizures, and 136 patients (39.3%) had a seizure reduction of 25% or less.

The authors reviewed medical records for children who were implanted with a VNS therapy device between April 1995 and April 2010. The children were ages 6 months to 17.9 years at implantation. All patients had taken a mean of 6.9 antiepileptic drugs (AEDs) before implantation, and 45% of patients had predominantly generalized seizures. The investigators assessed the change in frequency of the children’s predominant seizure type from baseline, defined as the three months before device implantation, to 12 months after implantation. They defined treatment response as a reduction in baseline seizure frequency of at least 50%. The study authors also examined the incidence of adverse events and noted clinicians’ assessments of the patients’ health outcomes, quality of life, and seizures.

The rate of reduction in baseline seizure frequency of at least 50% increased over time from 32.5% at six months to 37.6% at 12 months and to 43.8% at 24 months. The rate of this outcome “was higher in a subgroup of patients who had no change in AEDs during the study,” said Dr. Orosz, who is a Visiting Assistant Professor in the Department of Radiologic Sciences at the University of California, Los Angeles. Responder rates were “comparable to rates from randomized controlled trials of new AEDs in adult and pediatric patients with drug-resistant epilepsy,” she concluded.

—Amy Karon

Adjunctive vagus nerve stimulation (VNS) therapy may significantly reduce seizure activity for more than one-third of children with drug-resistant epilepsy, according to a large, retrospective, multicenter study, which was published in the October issue of Epilepsia.

Iren Orosz, MD, a pediatrician at the Medical University of Lübeck, Germany, and her colleagues at 11 medical centers across Europe found that 130 (37.6%) of 346 patients with drug-resistant epilepsy had at least a 50% reduction in seizures 12 months after being implanted with a VNS device. This group of patients included 19 (5.5%) who became seizure free and 111 (32.1%) who achieved a 50% to 99% reduction in seizure frequency. A total of 59 patients (17.1%) had a 25% to 49% reduction in seizures, and 136 patients (39.3%) had a seizure reduction of 25% or less.

The authors reviewed medical records for children who were implanted with a VNS therapy device between April 1995 and April 2010. The children were ages 6 months to 17.9 years at implantation. All patients had taken a mean of 6.9 antiepileptic drugs (AEDs) before implantation, and 45% of patients had predominantly generalized seizures. The investigators assessed the change in frequency of the children’s predominant seizure type from baseline, defined as the three months before device implantation, to 12 months after implantation. They defined treatment response as a reduction in baseline seizure frequency of at least 50%. The study authors also examined the incidence of adverse events and noted clinicians’ assessments of the patients’ health outcomes, quality of life, and seizures.

The rate of reduction in baseline seizure frequency of at least 50% increased over time from 32.5% at six months to 37.6% at 12 months and to 43.8% at 24 months. The rate of this outcome “was higher in a subgroup of patients who had no change in AEDs during the study,” said Dr. Orosz, who is a Visiting Assistant Professor in the Department of Radiologic Sciences at the University of California, Los Angeles. Responder rates were “comparable to rates from randomized controlled trials of new AEDs in adult and pediatric patients with drug-resistant epilepsy,” she concluded.

—Amy Karon

Adjunctive vagus nerve stimulation (VNS) therapy may significantly reduce seizure activity for more than one-third of children with drug-resistant epilepsy, according to a large, retrospective, multicenter study, which was published in the October issue of Epilepsia.

Iren Orosz, MD, a pediatrician at the Medical University of Lübeck, Germany, and her colleagues at 11 medical centers across Europe found that 130 (37.6%) of 346 patients with drug-resistant epilepsy had at least a 50% reduction in seizures 12 months after being implanted with a VNS device. This group of patients included 19 (5.5%) who became seizure free and 111 (32.1%) who achieved a 50% to 99% reduction in seizure frequency. A total of 59 patients (17.1%) had a 25% to 49% reduction in seizures, and 136 patients (39.3%) had a seizure reduction of 25% or less.

The authors reviewed medical records for children who were implanted with a VNS therapy device between April 1995 and April 2010. The children were ages 6 months to 17.9 years at implantation. All patients had taken a mean of 6.9 antiepileptic drugs (AEDs) before implantation, and 45% of patients had predominantly generalized seizures. The investigators assessed the change in frequency of the children’s predominant seizure type from baseline, defined as the three months before device implantation, to 12 months after implantation. They defined treatment response as a reduction in baseline seizure frequency of at least 50%. The study authors also examined the incidence of adverse events and noted clinicians’ assessments of the patients’ health outcomes, quality of life, and seizures.

The rate of reduction in baseline seizure frequency of at least 50% increased over time from 32.5% at six months to 37.6% at 12 months and to 43.8% at 24 months. The rate of this outcome “was higher in a subgroup of patients who had no change in AEDs during the study,” said Dr. Orosz, who is a Visiting Assistant Professor in the Department of Radiologic Sciences at the University of California, Los Angeles. Responder rates were “comparable to rates from randomized controlled trials of new AEDs in adult and pediatric patients with drug-resistant epilepsy,” she concluded.

—Amy Karon

A study of twins with seizures confirms the genetic basis of idiopathic generalized epilepsy, genetic epilepsy with febrile seizures plus, and focal epilepsies, investigators reported online ahead of print August 8 in Neurology.

The analysis did not support a genetic basis for benign epilepsy with centrotemporal spikes (BECTS) because of a lack of concordance between monozygotic pairs of twins with the disorder, said Lata Vadlamudi, PhD, Senior Lecturer at the University of Queensland in Brisbane, Australia, and her associates.

The researchers calculated casewise concordance estimates for epilepsy syndromes in 558 pairs of twins with suspected epilepsy, 418 of whom had confirmed seizures. They grouped the participants based on the 2010 International League Against Epilepsy (ILAE) scheme and incorporated molecular data when applicable.

Genetics of BECTS May Be Complex
The estimated concordance for monozygotic twins exceeded that for dizygotic twins for idiopathic generalized epilepsies (0.77 vs 0.35), genetic epilepsy with febrile seizures plus (0.85 vs 0.25), and focal epilepsies (0.40 vs 0.03), the researchers reported.

Applying the 2010 ILAE scheme also confirmed genetic influences for syndromes classified as genetic, and 10.9% of individuals tested had large-effect mutations in known epilepsy genes or had validated susceptibility alleles. Mutations most often involved the SCN1A gene, which is seen as the most clinically relevant gene in epilepsy, they said.

The study also found “striking monozygotic and dizygotic discordance” for BECTS, which has been presumed to have a genetic basis, said the researchers. “Our analysis of the BECTS twins ... highlighted that the etiology and genetics of BECTS are more complicated than initially conceptualized.”

For patients with epilepsy, the results “highlight the potential to integrate well-established clinical data with molecular genetic findings and pave the way for targeted next-generation sequencing of large cohorts, which is likely to be the next phase in diagnosis, treatment guidance, and genetic counseling,” said Dr. Vadlamudi.

Study Illuminates Genetic Complexities of Epilepsy
The most common epilepsy syndromes do not follow a straightforward Mendelian inheritance pattern, but instead involve combinations of large-effect and small-effect alleles and environmental factors. This twin study illuminated the genetic complexities of epilepsy and the influence of genetic variance on complex phenotypes, said Renzo Guerrini, MD, a neurologist at the University of Florence in Italy, and Jeffrey Buchhalter, MD, PhD, a neurologist at the Alberta Children’s Hospital in Calgary, Canada, in an accompanying editorial.

The study confirmed the strong genetic component of genetic epilepsy with febrile seizures plus and revealed high monozygotic concordance for the syndrome, the neurologists noted. In addition, the analysis found “compelling evidence” for a strong genetic role in generalized epilepsy, corroborating the concept of genetic epilepsy and the role of genes in some nonlesional focal epilepsies.

But it remains unclear whether current classifications for epilepsy reflect the molecular profiles of these syndromes, said the coauthors. The category of genetic epilepsy might be arbitrary, for example, “as what is presumed to be symptomatic today may be revealed as genetic after molecular screening,” said Drs. Guerrini and Buchhalter.

The structural/metabolic epilepsy category also is heterogeneous, encompassing generalized and localized brain malformations that are determined by the time of origin of neurons with abnormal migration patterns. “This suggests the need for a category that includes the genetic defect and interposed structural abnormality,” Drs. Guerrini and Buchhalter added.

The lack of concordance for monozygotic twins with benign epilepsy with centrotemporal spikes also contradicts prior reports that BECTS is primarily genetic, they noted. But perhaps the current study did not include enough twins with BECTS to capture those with rare monozygotic inheritance, or perhaps postzygotic mutations led to genetic discordance in twin pairs, Drs. Guerrini and Buchhalter concluded.

—Amy Karon

A study of twins with seizures confirms the genetic basis of idiopathic generalized epilepsy, genetic epilepsy with febrile seizures plus, and focal epilepsies, investigators reported online ahead of print August 8 in Neurology.

The analysis did not support a genetic basis for benign epilepsy with centrotemporal spikes (BECTS) because of a lack of concordance between monozygotic pairs of twins with the disorder, said Lata Vadlamudi, PhD, Senior Lecturer at the University of Queensland in Brisbane, Australia, and her associates.

The researchers calculated casewise concordance estimates for epilepsy syndromes in 558 pairs of twins with suspected epilepsy, 418 of whom had confirmed seizures. They grouped the participants based on the 2010 International League Against Epilepsy (ILAE) scheme and incorporated molecular data when applicable.

Genetics of BECTS May Be Complex
The estimated concordance for monozygotic twins exceeded that for dizygotic twins for idiopathic generalized epilepsies (0.77 vs 0.35), genetic epilepsy with febrile seizures plus (0.85 vs 0.25), and focal epilepsies (0.40 vs 0.03), the researchers reported.

Applying the 2010 ILAE scheme also confirmed genetic influences for syndromes classified as genetic, and 10.9% of individuals tested had large-effect mutations in known epilepsy genes or had validated susceptibility alleles. Mutations most often involved the SCN1A gene, which is seen as the most clinically relevant gene in epilepsy, they said.

The study also found “striking monozygotic and dizygotic discordance” for BECTS, which has been presumed to have a genetic basis, said the researchers. “Our analysis of the BECTS twins ... highlighted that the etiology and genetics of BECTS are more complicated than initially conceptualized.”

For patients with epilepsy, the results “highlight the potential to integrate well-established clinical data with molecular genetic findings and pave the way for targeted next-generation sequencing of large cohorts, which is likely to be the next phase in diagnosis, treatment guidance, and genetic counseling,” said Dr. Vadlamudi.

Study Illuminates Genetic Complexities of Epilepsy
The most common epilepsy syndromes do not follow a straightforward Mendelian inheritance pattern, but instead involve combinations of large-effect and small-effect alleles and environmental factors. This twin study illuminated the genetic complexities of epilepsy and the influence of genetic variance on complex phenotypes, said Renzo Guerrini, MD, a neurologist at the University of Florence in Italy, and Jeffrey Buchhalter, MD, PhD, a neurologist at the Alberta Children’s Hospital in Calgary, Canada, in an accompanying editorial.

The study confirmed the strong genetic component of genetic epilepsy with febrile seizures plus and revealed high monozygotic concordance for the syndrome, the neurologists noted. In addition, the analysis found “compelling evidence” for a strong genetic role in generalized epilepsy, corroborating the concept of genetic epilepsy and the role of genes in some nonlesional focal epilepsies.

But it remains unclear whether current classifications for epilepsy reflect the molecular profiles of these syndromes, said the coauthors. The category of genetic epilepsy might be arbitrary, for example, “as what is presumed to be symptomatic today may be revealed as genetic after molecular screening,” said Drs. Guerrini and Buchhalter.

The structural/metabolic epilepsy category also is heterogeneous, encompassing generalized and localized brain malformations that are determined by the time of origin of neurons with abnormal migration patterns. “This suggests the need for a category that includes the genetic defect and interposed structural abnormality,” Drs. Guerrini and Buchhalter added.

The lack of concordance for monozygotic twins with benign epilepsy with centrotemporal spikes also contradicts prior reports that BECTS is primarily genetic, they noted. But perhaps the current study did not include enough twins with BECTS to capture those with rare monozygotic inheritance, or perhaps postzygotic mutations led to genetic discordance in twin pairs, Drs. Guerrini and Buchhalter concluded.

—Amy Karon

A study of twins with seizures confirms the genetic basis of idiopathic generalized epilepsy, genetic epilepsy with febrile seizures plus, and focal epilepsies, investigators reported online ahead of print August 8 in Neurology.

The analysis did not support a genetic basis for benign epilepsy with centrotemporal spikes (BECTS) because of a lack of concordance between monozygotic pairs of twins with the disorder, said Lata Vadlamudi, PhD, Senior Lecturer at the University of Queensland in Brisbane, Australia, and her associates.

The researchers calculated casewise concordance estimates for epilepsy syndromes in 558 pairs of twins with suspected epilepsy, 418 of whom had confirmed seizures. They grouped the participants based on the 2010 International League Against Epilepsy (ILAE) scheme and incorporated molecular data when applicable.

Genetics of BECTS May Be Complex
The estimated concordance for monozygotic twins exceeded that for dizygotic twins for idiopathic generalized epilepsies (0.77 vs 0.35), genetic epilepsy with febrile seizures plus (0.85 vs 0.25), and focal epilepsies (0.40 vs 0.03), the researchers reported.

Applying the 2010 ILAE scheme also confirmed genetic influences for syndromes classified as genetic, and 10.9% of individuals tested had large-effect mutations in known epilepsy genes or had validated susceptibility alleles. Mutations most often involved the SCN1A gene, which is seen as the most clinically relevant gene in epilepsy, they said.

The study also found “striking monozygotic and dizygotic discordance” for BECTS, which has been presumed to have a genetic basis, said the researchers. “Our analysis of the BECTS twins ... highlighted that the etiology and genetics of BECTS are more complicated than initially conceptualized.”

For patients with epilepsy, the results “highlight the potential to integrate well-established clinical data with molecular genetic findings and pave the way for targeted next-generation sequencing of large cohorts, which is likely to be the next phase in diagnosis, treatment guidance, and genetic counseling,” said Dr. Vadlamudi.

Study Illuminates Genetic Complexities of Epilepsy
The most common epilepsy syndromes do not follow a straightforward Mendelian inheritance pattern, but instead involve combinations of large-effect and small-effect alleles and environmental factors. This twin study illuminated the genetic complexities of epilepsy and the influence of genetic variance on complex phenotypes, said Renzo Guerrini, MD, a neurologist at the University of Florence in Italy, and Jeffrey Buchhalter, MD, PhD, a neurologist at the Alberta Children’s Hospital in Calgary, Canada, in an accompanying editorial.

The study confirmed the strong genetic component of genetic epilepsy with febrile seizures plus and revealed high monozygotic concordance for the syndrome, the neurologists noted. In addition, the analysis found “compelling evidence” for a strong genetic role in generalized epilepsy, corroborating the concept of genetic epilepsy and the role of genes in some nonlesional focal epilepsies.

But it remains unclear whether current classifications for epilepsy reflect the molecular profiles of these syndromes, said the coauthors. The category of genetic epilepsy might be arbitrary, for example, “as what is presumed to be symptomatic today may be revealed as genetic after molecular screening,” said Drs. Guerrini and Buchhalter.

The structural/metabolic epilepsy category also is heterogeneous, encompassing generalized and localized brain malformations that are determined by the time of origin of neurons with abnormal migration patterns. “This suggests the need for a category that includes the genetic defect and interposed structural abnormality,” Drs. Guerrini and Buchhalter added.

The lack of concordance for monozygotic twins with benign epilepsy with centrotemporal spikes also contradicts prior reports that BECTS is primarily genetic, they noted. But perhaps the current study did not include enough twins with BECTS to capture those with rare monozygotic inheritance, or perhaps postzygotic mutations led to genetic discordance in twin pairs, Drs. Guerrini and Buchhalter concluded.

—Amy Karon