Application of Pediatric Epilepsy Surgery Expands as Understanding Increases

WASHINGTON, DC—Neurologists are considering resective surgery as a treatment for children with epilepsy more often than they have in the past, according to research presented at the 67th Annual Meeting of the American Epilepsy Society. “The change in surgical landscape in kids does not appear to be epidemiologic, but rather reflects a change in us and [in] how we look at the problem,” said Howard L. Weiner, MD.

Neurologists’ understanding of pediatric epilepsy surgery has changed during the past 20 years. The treatment had long been limited to children with brain lesions, focal cortical dysplasias, epilepsy-associated tumors, cavernous malformations, and hemispheric pathology. But neurologists are now performing surgery on children with more challenging types of epilepsy such as bilateral polymicrogyria and tuberous sclerosis.

A New Analysis of Surgery’s Risks and Benefits for Children
Neurologists’ perception of pediatric epilepsy surgery’s risk–benefit profile has evolved, “tilting the balance toward favoring surgery,” said Dr. Weiner, Professor of Neurosurgery at the New York University Langone Medical Center. Researchers have concluded that uncontrolled epilepsy is harmful for the developing brain, for the child’s and the family’s quality of life, and for the child’s life expectancy. Evidence indicates that successful epilepsy surgery can improve brain development and children’s quality of life. Other research suggests that pediatric epilepsy surgery is safe and can be cost-effective.

After conducting a prospective study of 198 children in 2012, investigators concluded that “uncontrolled seizures impair cognitive function, with effects being most severe in infancy and lessening with increasing age at onset.” The results underscored “the need for early, aggressive treatment and seizure control in infants and young children,” they added.

Overall mortality in children with epilepsy is double that of children in the general population because of sudden and seizure-related deaths, said Dr. Weiner. The rate of sudden unexpected death in epilepsy is similar to or higher than the rate of sudden infant death syndrome, “which gets a tremendous amount of attention in the pediatric world,” he added.

Other data suggest that pediatric epilepsy surgery affects children’s development. In one investigation, children’s seizure frequency and developmental quotient improved after surgery. Developmental status before surgery predicted developmental function after surgery, which suggests that neurologists should treat children before their development regresses, said Dr. Weiner. Another trial suggested that children with epileptic spasms who underwent surgery at a younger age had the largest increase in developmental quotient after surgery, compared with children who underwent surgery later. These data call the conventional thinking about pediatric epilepsy surgery into question, said Dr. Weiner.

Surgery Is Safe and May Be Cost Effective
The complication rate of pediatric epilepsy surgery is similar to that of other types of pediatric neurosurgery. Dr. Weiner and colleagues analyzed data for resective surgeries performed on children at the New York University Langone Medical Center during a 12-year period. The researchers observed no mortality. The number of complications was significantly lower during the second half of the study period, compared with the first half, although the patient population did not change significantly. “Perhaps there was a learning curve,” said Dr. Weiner.

Other studies indicate that epilepsy surgery can be cost-effective. Investigators in Toronto found that surgical treatment resulted in a greater reduction in seizure frequency, compared with medical therapy, and was a cost-effective treatment option in children with intractable epilepsy. Researchers at the Cleveland Clinic found that patients’ hospitalization rates and emergency room visits decreased significantly after surgery.

An Expanding Pool of Surgical Candidates
Recent research has enabled neurologists to consider surgery for children who previously would not have been considered candidates for surgery. Physicians at the Cleveland Clinic successfully performed surgery on patients for epilepsy that resulted from early brain lesions. The patients had generalized EEG findings, which usually are a contraindication for surgery, said Dr. Weiner. The investigators found that focal epilepsy surgery may be successful for certain children with a congenital or early-acquired brain lesion, despite abundant generalized or bilateral epileptiform discharges on EEG.

Other studies have focused new attention on children with tuberous sclerosis. “Multiple or bilateral seizure foci are not necessarily a contraindication to surgery, and children within this larger population may be candidates for focal surgery,” said Dr. Weiner.

Improved preoperative diagnostic evaluations are a major reason for the expanding pool of surgical candidates. MRI, PET, magnetoencephalography, single-photon emission computed tomography, and fMRI have “gotten better over the last 20 years, and now we can see the surgical substrate much better,” said Dr. Weiner. For example, 7-T MRI with high field strength has revealed previously uncharacterized brain lesions in patients with tuberous sclerosis complex.

Neurologists also have become more comfortable with invasive EEG monitoring in children with challenging epilepsies. Epilepsy centers each have a different level of comfort with this monitoring, said Dr. Weiner. Some neurologists have used the monitoring for children with nonconcordant and nonlocalizing MRI. A more controversial application would be for determining which of multiple lesions is the epileptic focus in a child. Invasive EEG monitoring also could help define the relationship of the focus to a structural lesion on MRI.

In addition, neurologists have become more willing to consider aggressive surgical resections, even if they are likely to result in neurologic deficits. “Epilepsy surgery is a quality-of-life intervention, and we’re trading off a potential physical deficit like a visual field cut or a mild hemiparesis for the idea of seizure freedom and developmental improvement,” said Dr. Weiner. “This point is unique to pediatric medicine, where the mandate to act for us is much stronger when the potential impact we can have, with respect to the child’s development, may be lifelong.”

Rates of Postsurgical Seizure Freedom May Decline Over Time
When considering surgery as a treatment option, neurologists must consider what the procedure’s long-term efficacy is likely to be. Researchers at the Cleveland Clinic examined data for all the patients that they had studied with intracranial electrodes. They found that the rate of seizure freedom decreased with time. At two years after surgery, approximately two-thirds of patients were seizure free. The rate of seizure freedom was 50% at five years and approximately 40% at 10 years.

The investigators hypothesized that early postresection failures may result from incomplete resections or from missing the focus. Later failures may result from “yet-unknown mechanisms, including the presence of more extensive but dormant proepileptic cortex,” said Dr. Weiner. “We have to be well aware of [this issue] as we’re taking on some of these more challenging and diffuse pathologies. You have to discuss this with the families.

“Although the spectrum of epilepsy surgery in children appears to be expanding, we absolutely need to exercise great caution in approaching all these cases, and our default presumption should be one of reluctance” to perform surgery, said Dr. Weiner.

Surgery in young children is potentially dangerous, and many children will require intracranial studies that may be too invasive, he noted. For certain children, surgery may not yield a better long-term outcome than medical therapy. And extensive evaluation and treatment in a hospital can be cost-prohibitive.

“These children are best evaluated at comprehensive epilepsy centers where the risk–benefit analysis can be determined collectively by the treating team after an extensive evaluation,” Dr. Weiner concluded.

—Erik Greb

WASHINGTON, DC—Neurologists are considering resective surgery as a treatment for children with epilepsy more often than they have in the past, according to research presented at the 67th Annual Meeting of the American Epilepsy Society. “The change in surgical landscape in kids does not appear to be epidemiologic, but rather reflects a change in us and [in] how we look at the problem,” said Howard L. Weiner, MD.

Neurologists’ understanding of pediatric epilepsy surgery has changed during the past 20 years. The treatment had long been limited to children with brain lesions, focal cortical dysplasias, epilepsy-associated tumors, cavernous malformations, and hemispheric pathology. But neurologists are now performing surgery on children with more challenging types of epilepsy such as bilateral polymicrogyria and tuberous sclerosis.

A New Analysis of Surgery’s Risks and Benefits for Children
Neurologists’ perception of pediatric epilepsy surgery’s risk–benefit profile has evolved, “tilting the balance toward favoring surgery,” said Dr. Weiner, Professor of Neurosurgery at the New York University Langone Medical Center. Researchers have concluded that uncontrolled epilepsy is harmful for the developing brain, for the child’s and the family’s quality of life, and for the child’s life expectancy. Evidence indicates that successful epilepsy surgery can improve brain development and children’s quality of life. Other research suggests that pediatric epilepsy surgery is safe and can be cost-effective.

After conducting a prospective study of 198 children in 2012, investigators concluded that “uncontrolled seizures impair cognitive function, with effects being most severe in infancy and lessening with increasing age at onset.” The results underscored “the need for early, aggressive treatment and seizure control in infants and young children,” they added.

Overall mortality in children with epilepsy is double that of children in the general population because of sudden and seizure-related deaths, said Dr. Weiner. The rate of sudden unexpected death in epilepsy is similar to or higher than the rate of sudden infant death syndrome, “which gets a tremendous amount of attention in the pediatric world,” he added.

Other data suggest that pediatric epilepsy surgery affects children’s development. In one investigation, children’s seizure frequency and developmental quotient improved after surgery. Developmental status before surgery predicted developmental function after surgery, which suggests that neurologists should treat children before their development regresses, said Dr. Weiner. Another trial suggested that children with epileptic spasms who underwent surgery at a younger age had the largest increase in developmental quotient after surgery, compared with children who underwent surgery later. These data call the conventional thinking about pediatric epilepsy surgery into question, said Dr. Weiner.

Surgery Is Safe and May Be Cost Effective
The complication rate of pediatric epilepsy surgery is similar to that of other types of pediatric neurosurgery. Dr. Weiner and colleagues analyzed data for resective surgeries performed on children at the New York University Langone Medical Center during a 12-year period. The researchers observed no mortality. The number of complications was significantly lower during the second half of the study period, compared with the first half, although the patient population did not change significantly. “Perhaps there was a learning curve,” said Dr. Weiner.

Other studies indicate that epilepsy surgery can be cost-effective. Investigators in Toronto found that surgical treatment resulted in a greater reduction in seizure frequency, compared with medical therapy, and was a cost-effective treatment option in children with intractable epilepsy. Researchers at the Cleveland Clinic found that patients’ hospitalization rates and emergency room visits decreased significantly after surgery.

An Expanding Pool of Surgical Candidates
Recent research has enabled neurologists to consider surgery for children who previously would not have been considered candidates for surgery. Physicians at the Cleveland Clinic successfully performed surgery on patients for epilepsy that resulted from early brain lesions. The patients had generalized EEG findings, which usually are a contraindication for surgery, said Dr. Weiner. The investigators found that focal epilepsy surgery may be successful for certain children with a congenital or early-acquired brain lesion, despite abundant generalized or bilateral epileptiform discharges on EEG.

Other studies have focused new attention on children with tuberous sclerosis. “Multiple or bilateral seizure foci are not necessarily a contraindication to surgery, and children within this larger population may be candidates for focal surgery,” said Dr. Weiner.

Improved preoperative diagnostic evaluations are a major reason for the expanding pool of surgical candidates. MRI, PET, magnetoencephalography, single-photon emission computed tomography, and fMRI have “gotten better over the last 20 years, and now we can see the surgical substrate much better,” said Dr. Weiner. For example, 7-T MRI with high field strength has revealed previously uncharacterized brain lesions in patients with tuberous sclerosis complex.

Neurologists also have become more comfortable with invasive EEG monitoring in children with challenging epilepsies. Epilepsy centers each have a different level of comfort with this monitoring, said Dr. Weiner. Some neurologists have used the monitoring for children with nonconcordant and nonlocalizing MRI. A more controversial application would be for determining which of multiple lesions is the epileptic focus in a child. Invasive EEG monitoring also could help define the relationship of the focus to a structural lesion on MRI.

In addition, neurologists have become more willing to consider aggressive surgical resections, even if they are likely to result in neurologic deficits. “Epilepsy surgery is a quality-of-life intervention, and we’re trading off a potential physical deficit like a visual field cut or a mild hemiparesis for the idea of seizure freedom and developmental improvement,” said Dr. Weiner. “This point is unique to pediatric medicine, where the mandate to act for us is much stronger when the potential impact we can have, with respect to the child’s development, may be lifelong.”

Rates of Postsurgical Seizure Freedom May Decline Over Time
When considering surgery as a treatment option, neurologists must consider what the procedure’s long-term efficacy is likely to be. Researchers at the Cleveland Clinic examined data for all the patients that they had studied with intracranial electrodes. They found that the rate of seizure freedom decreased with time. At two years after surgery, approximately two-thirds of patients were seizure free. The rate of seizure freedom was 50% at five years and approximately 40% at 10 years.

The investigators hypothesized that early postresection failures may result from incomplete resections or from missing the focus. Later failures may result from “yet-unknown mechanisms, including the presence of more extensive but dormant proepileptic cortex,” said Dr. Weiner. “We have to be well aware of [this issue] as we’re taking on some of these more challenging and diffuse pathologies. You have to discuss this with the families.

“Although the spectrum of epilepsy surgery in children appears to be expanding, we absolutely need to exercise great caution in approaching all these cases, and our default presumption should be one of reluctance” to perform surgery, said Dr. Weiner.

Surgery in young children is potentially dangerous, and many children will require intracranial studies that may be too invasive, he noted. For certain children, surgery may not yield a better long-term outcome than medical therapy. And extensive evaluation and treatment in a hospital can be cost-prohibitive.

“These children are best evaluated at comprehensive epilepsy centers where the risk–benefit analysis can be determined collectively by the treating team after an extensive evaluation,” Dr. Weiner concluded.

—Erik Greb

WASHINGTON, DC—Neurologists are considering resective surgery as a treatment for children with epilepsy more often than they have in the past, according to research presented at the 67th Annual Meeting of the American Epilepsy Society. “The change in surgical landscape in kids does not appear to be epidemiologic, but rather reflects a change in us and [in] how we look at the problem,” said Howard L. Weiner, MD.

Neurologists’ understanding of pediatric epilepsy surgery has changed during the past 20 years. The treatment had long been limited to children with brain lesions, focal cortical dysplasias, epilepsy-associated tumors, cavernous malformations, and hemispheric pathology. But neurologists are now performing surgery on children with more challenging types of epilepsy such as bilateral polymicrogyria and tuberous sclerosis.

A New Analysis of Surgery’s Risks and Benefits for Children
Neurologists’ perception of pediatric epilepsy surgery’s risk–benefit profile has evolved, “tilting the balance toward favoring surgery,” said Dr. Weiner, Professor of Neurosurgery at the New York University Langone Medical Center. Researchers have concluded that uncontrolled epilepsy is harmful for the developing brain, for the child’s and the family’s quality of life, and for the child’s life expectancy. Evidence indicates that successful epilepsy surgery can improve brain development and children’s quality of life. Other research suggests that pediatric epilepsy surgery is safe and can be cost-effective.

After conducting a prospective study of 198 children in 2012, investigators concluded that “uncontrolled seizures impair cognitive function, with effects being most severe in infancy and lessening with increasing age at onset.” The results underscored “the need for early, aggressive treatment and seizure control in infants and young children,” they added.

Overall mortality in children with epilepsy is double that of children in the general population because of sudden and seizure-related deaths, said Dr. Weiner. The rate of sudden unexpected death in epilepsy is similar to or higher than the rate of sudden infant death syndrome, “which gets a tremendous amount of attention in the pediatric world,” he added.

Other data suggest that pediatric epilepsy surgery affects children’s development. In one investigation, children’s seizure frequency and developmental quotient improved after surgery. Developmental status before surgery predicted developmental function after surgery, which suggests that neurologists should treat children before their development regresses, said Dr. Weiner. Another trial suggested that children with epileptic spasms who underwent surgery at a younger age had the largest increase in developmental quotient after surgery, compared with children who underwent surgery later. These data call the conventional thinking about pediatric epilepsy surgery into question, said Dr. Weiner.

Surgery Is Safe and May Be Cost Effective
The complication rate of pediatric epilepsy surgery is similar to that of other types of pediatric neurosurgery. Dr. Weiner and colleagues analyzed data for resective surgeries performed on children at the New York University Langone Medical Center during a 12-year period. The researchers observed no mortality. The number of complications was significantly lower during the second half of the study period, compared with the first half, although the patient population did not change significantly. “Perhaps there was a learning curve,” said Dr. Weiner.

Other studies indicate that epilepsy surgery can be cost-effective. Investigators in Toronto found that surgical treatment resulted in a greater reduction in seizure frequency, compared with medical therapy, and was a cost-effective treatment option in children with intractable epilepsy. Researchers at the Cleveland Clinic found that patients’ hospitalization rates and emergency room visits decreased significantly after surgery.

An Expanding Pool of Surgical Candidates
Recent research has enabled neurologists to consider surgery for children who previously would not have been considered candidates for surgery. Physicians at the Cleveland Clinic successfully performed surgery on patients for epilepsy that resulted from early brain lesions. The patients had generalized EEG findings, which usually are a contraindication for surgery, said Dr. Weiner. The investigators found that focal epilepsy surgery may be successful for certain children with a congenital or early-acquired brain lesion, despite abundant generalized or bilateral epileptiform discharges on EEG.

Other studies have focused new attention on children with tuberous sclerosis. “Multiple or bilateral seizure foci are not necessarily a contraindication to surgery, and children within this larger population may be candidates for focal surgery,” said Dr. Weiner.

Improved preoperative diagnostic evaluations are a major reason for the expanding pool of surgical candidates. MRI, PET, magnetoencephalography, single-photon emission computed tomography, and fMRI have “gotten better over the last 20 years, and now we can see the surgical substrate much better,” said Dr. Weiner. For example, 7-T MRI with high field strength has revealed previously uncharacterized brain lesions in patients with tuberous sclerosis complex.

Neurologists also have become more comfortable with invasive EEG monitoring in children with challenging epilepsies. Epilepsy centers each have a different level of comfort with this monitoring, said Dr. Weiner. Some neurologists have used the monitoring for children with nonconcordant and nonlocalizing MRI. A more controversial application would be for determining which of multiple lesions is the epileptic focus in a child. Invasive EEG monitoring also could help define the relationship of the focus to a structural lesion on MRI.

In addition, neurologists have become more willing to consider aggressive surgical resections, even if they are likely to result in neurologic deficits. “Epilepsy surgery is a quality-of-life intervention, and we’re trading off a potential physical deficit like a visual field cut or a mild hemiparesis for the idea of seizure freedom and developmental improvement,” said Dr. Weiner. “This point is unique to pediatric medicine, where the mandate to act for us is much stronger when the potential impact we can have, with respect to the child’s development, may be lifelong.”

Rates of Postsurgical Seizure Freedom May Decline Over Time
When considering surgery as a treatment option, neurologists must consider what the procedure’s long-term efficacy is likely to be. Researchers at the Cleveland Clinic examined data for all the patients that they had studied with intracranial electrodes. They found that the rate of seizure freedom decreased with time. At two years after surgery, approximately two-thirds of patients were seizure free. The rate of seizure freedom was 50% at five years and approximately 40% at 10 years.

The investigators hypothesized that early postresection failures may result from incomplete resections or from missing the focus. Later failures may result from “yet-unknown mechanisms, including the presence of more extensive but dormant proepileptic cortex,” said Dr. Weiner. “We have to be well aware of [this issue] as we’re taking on some of these more challenging and diffuse pathologies. You have to discuss this with the families.

“Although the spectrum of epilepsy surgery in children appears to be expanding, we absolutely need to exercise great caution in approaching all these cases, and our default presumption should be one of reluctance” to perform surgery, said Dr. Weiner.

Surgery in young children is potentially dangerous, and many children will require intracranial studies that may be too invasive, he noted. For certain children, surgery may not yield a better long-term outcome than medical therapy. And extensive evaluation and treatment in a hospital can be cost-prohibitive.

“These children are best evaluated at comprehensive epilepsy centers where the risk–benefit analysis can be determined collectively by the treating team after an extensive evaluation,” Dr. Weiner concluded.

—Erik Greb