Literature Monitor

In this study, investigators asked 77 parents who had children with epilepsy and 173 parents without affected offspring who were from families that included individuals with the disease if they were interested in genetic testing for their offspring.  Among families with affected children, 71% to 86% expressed interest in diagnostic testing. By comparison, 53% to 74% of parents who had no affected children expressed interest in predictive genetic testing. Among parents, there was strong agreement regarding an interest in genetic testing for themselves versus their offspring (90%-94%). However, mothers and fathers only expressed moderate agreement in their interest for a test that had clinical utility, and only a “fair” interest in genetic testing if there was no clinical utility.

Caminiti CB, Hesdorffer DC, Shostak S, et al. Parents’ interest in genetic testing of their offspring in multiplex epilepsy families. Epilepsia. 2016;57(2):279-287.

In this study, investigators asked 77 parents who had children with epilepsy and 173 parents without affected offspring who were from families that included individuals with the disease if they were interested in genetic testing for their offspring.  Among families with affected children, 71% to 86% expressed interest in diagnostic testing. By comparison, 53% to 74% of parents who had no affected children expressed interest in predictive genetic testing. Among parents, there was strong agreement regarding an interest in genetic testing for themselves versus their offspring (90%-94%). However, mothers and fathers only expressed moderate agreement in their interest for a test that had clinical utility, and only a “fair” interest in genetic testing if there was no clinical utility.

Caminiti CB, Hesdorffer DC, Shostak S, et al. Parents’ interest in genetic testing of their offspring in multiplex epilepsy families. Epilepsia. 2016;57(2):279-287.

In this study, investigators asked 77 parents who had children with epilepsy and 173 parents without affected offspring who were from families that included individuals with the disease if they were interested in genetic testing for their offspring.  Among families with affected children, 71% to 86% expressed interest in diagnostic testing. By comparison, 53% to 74% of parents who had no affected children expressed interest in predictive genetic testing. Among parents, there was strong agreement regarding an interest in genetic testing for themselves versus their offspring (90%-94%). However, mothers and fathers only expressed moderate agreement in their interest for a test that had clinical utility, and only a “fair” interest in genetic testing if there was no clinical utility.

Caminiti CB, Hesdorffer DC, Shostak S, et al. Parents’ interest in genetic testing of their offspring in multiplex epilepsy families. Epilepsia. 2016;57(2):279-287.

Researchers examined data of US Adults from the 2010 and 2013 National Health Interview Surveys and found that adults with active epilepsy:

• Were more likely to be insured by Medicaid; report being disabled; and report transportation barriers
• Were less likely to have private health insurance; be employed; or afford medication, vision, and dental care
• Experience greater barriers to health care access.

Thurman DJ, Kobau R, Luo YH, Helmers SL, Zack MM. Health-care access among adults with epilepsy: The U.S. National Health Interview Survey, 2010 and 2013. Epilepsy Behav. 2015: doi: 10.1015/j.yebeh.2015.10.028.

Researchers examined data of US Adults from the 2010 and 2013 National Health Interview Surveys and found that adults with active epilepsy:

• Were more likely to be insured by Medicaid; report being disabled; and report transportation barriers
• Were less likely to have private health insurance; be employed; or afford medication, vision, and dental care
• Experience greater barriers to health care access.

Thurman DJ, Kobau R, Luo YH, Helmers SL, Zack MM. Health-care access among adults with epilepsy: The U.S. National Health Interview Survey, 2010 and 2013. Epilepsy Behav. 2015: doi: 10.1015/j.yebeh.2015.10.028.

Researchers examined data of US Adults from the 2010 and 2013 National Health Interview Surveys and found that adults with active epilepsy:

• Were more likely to be insured by Medicaid; report being disabled; and report transportation barriers
• Were less likely to have private health insurance; be employed; or afford medication, vision, and dental care
• Experience greater barriers to health care access.

Thurman DJ, Kobau R, Luo YH, Helmers SL, Zack MM. Health-care access among adults with epilepsy: The U.S. National Health Interview Survey, 2010 and 2013. Epilepsy Behav. 2015: doi: 10.1015/j.yebeh.2015.10.028.

Long-term seizure outcomes in adults with childhood-onset epilepsy are excellent, according to a study published in the November issue of Epilepsia. The study found that while patients with childhood onset had excellent remission rates in adulthood, long-term results depending on etiology did raise concerns, most notably in cerebrovascular disease. “The presence of imaging abnormalities suggestive of vascular disease may put these subjects at higher risk for clinically evident stroke and cognitive changes as they age,” said Matti Sillanpää, MD, and colleagues. Dr. Sillanpää is a Senior Research Scientist at the University of Turku in Finland.

A population-based cohort of 245 patients with childhood-onset epilepsy was assessed for outcome at 45 years. In addition, 51 of 78 surviving subjects with uncomplicated epilepsy (ie, no neurologic impairment at onset) and 52 of 99 originally matched controls participated in a detailed evaluation that included EEG, imaging, and laboratory studies at 50 years.

Of the 179 surviving subjects, 61% were in terminal 10-year remission and 43% were in remission off medications. At 45 years, 95% of the idiopathic group, 72% of the cryptogenic group, and 47% of the remote symptomatic group were in terminal remission. Abnormal neurologic signs were significantly more common in subjects with uncomplicated epilepsy than in controls. Mortality during the period from 1992 to 2012 was higher in subjects (9%) than in controls (1%). The rate of MRI abnormalities was higher in subjects than in controls (risk ratio, 2.0), specifically including findings indicative of cerebrovascular disease.

In the 50-year follow-up study, the 47 remaining willing patients who had no neurologic impairment at onset were compared with a group of 50 controls. The previously epileptic group was shown to be more susceptible to neurologic disorders than the controls (73% vs 55%, respectively).

This finding is consistent with the MRI results of the subjects when examined at middle age, which showed a significantly higher rate of neurologic abnormalities on examinations than controls did. These changes, while often present in the general population, had an earlier onset in the epileptic population. These findings suggest that underlying etiology, seizures, and treatment may be responsible for these changes.

This study’s significance lies in the long and continuing duration of the follow-up. The extended study time allowed researchers to compare development between patients with epilepsy and the general population. As the epilepsy and control groups reach an age characteristic of cerebrovascular risk, further analysis is needed to determine if the concerns about MRI results translate to disease, said Dr. Sillanpää.

—Adaeze Stephanie Onyechi

Long-term seizure outcomes in adults with childhood-onset epilepsy are excellent, according to a study published in the November issue of Epilepsia. The study found that while patients with childhood onset had excellent remission rates in adulthood, long-term results depending on etiology did raise concerns, most notably in cerebrovascular disease. “The presence of imaging abnormalities suggestive of vascular disease may put these subjects at higher risk for clinically evident stroke and cognitive changes as they age,” said Matti Sillanpää, MD, and colleagues. Dr. Sillanpää is a Senior Research Scientist at the University of Turku in Finland.

A population-based cohort of 245 patients with childhood-onset epilepsy was assessed for outcome at 45 years. In addition, 51 of 78 surviving subjects with uncomplicated epilepsy (ie, no neurologic impairment at onset) and 52 of 99 originally matched controls participated in a detailed evaluation that included EEG, imaging, and laboratory studies at 50 years.

Of the 179 surviving subjects, 61% were in terminal 10-year remission and 43% were in remission off medications. At 45 years, 95% of the idiopathic group, 72% of the cryptogenic group, and 47% of the remote symptomatic group were in terminal remission. Abnormal neurologic signs were significantly more common in subjects with uncomplicated epilepsy than in controls. Mortality during the period from 1992 to 2012 was higher in subjects (9%) than in controls (1%). The rate of MRI abnormalities was higher in subjects than in controls (risk ratio, 2.0), specifically including findings indicative of cerebrovascular disease.

In the 50-year follow-up study, the 47 remaining willing patients who had no neurologic impairment at onset were compared with a group of 50 controls. The previously epileptic group was shown to be more susceptible to neurologic disorders than the controls (73% vs 55%, respectively).

This finding is consistent with the MRI results of the subjects when examined at middle age, which showed a significantly higher rate of neurologic abnormalities on examinations than controls did. These changes, while often present in the general population, had an earlier onset in the epileptic population. These findings suggest that underlying etiology, seizures, and treatment may be responsible for these changes.

This study’s significance lies in the long and continuing duration of the follow-up. The extended study time allowed researchers to compare development between patients with epilepsy and the general population. As the epilepsy and control groups reach an age characteristic of cerebrovascular risk, further analysis is needed to determine if the concerns about MRI results translate to disease, said Dr. Sillanpää.

—Adaeze Stephanie Onyechi

Long-term seizure outcomes in adults with childhood-onset epilepsy are excellent, according to a study published in the November issue of Epilepsia. The study found that while patients with childhood onset had excellent remission rates in adulthood, long-term results depending on etiology did raise concerns, most notably in cerebrovascular disease. “The presence of imaging abnormalities suggestive of vascular disease may put these subjects at higher risk for clinically evident stroke and cognitive changes as they age,” said Matti Sillanpää, MD, and colleagues. Dr. Sillanpää is a Senior Research Scientist at the University of Turku in Finland.

A population-based cohort of 245 patients with childhood-onset epilepsy was assessed for outcome at 45 years. In addition, 51 of 78 surviving subjects with uncomplicated epilepsy (ie, no neurologic impairment at onset) and 52 of 99 originally matched controls participated in a detailed evaluation that included EEG, imaging, and laboratory studies at 50 years.

Of the 179 surviving subjects, 61% were in terminal 10-year remission and 43% were in remission off medications. At 45 years, 95% of the idiopathic group, 72% of the cryptogenic group, and 47% of the remote symptomatic group were in terminal remission. Abnormal neurologic signs were significantly more common in subjects with uncomplicated epilepsy than in controls. Mortality during the period from 1992 to 2012 was higher in subjects (9%) than in controls (1%). The rate of MRI abnormalities was higher in subjects than in controls (risk ratio, 2.0), specifically including findings indicative of cerebrovascular disease.

In the 50-year follow-up study, the 47 remaining willing patients who had no neurologic impairment at onset were compared with a group of 50 controls. The previously epileptic group was shown to be more susceptible to neurologic disorders than the controls (73% vs 55%, respectively).

This finding is consistent with the MRI results of the subjects when examined at middle age, which showed a significantly higher rate of neurologic abnormalities on examinations than controls did. These changes, while often present in the general population, had an earlier onset in the epileptic population. These findings suggest that underlying etiology, seizures, and treatment may be responsible for these changes.

This study’s significance lies in the long and continuing duration of the follow-up. The extended study time allowed researchers to compare development between patients with epilepsy and the general population. As the epilepsy and control groups reach an age characteristic of cerebrovascular risk, further analysis is needed to determine if the concerns about MRI results translate to disease, said Dr. Sillanpää.

—Adaeze Stephanie Onyechi

Among adult patients with medically refractory partial-onset seizures, treatment with responsive neurostimulation is not associated with cognitive decline over two years, according to data published in the November issue of Epilepsia. The therapy may in fact induce small but significant improvements in naming among patients with neocortical seizure onset and modest improvements in verbal learning among patients with seizure onset in the mesial temporal lobe.

“These findings require replication but suggest potential cognitive therapeutic benefit associated with responsive neurostimulation,” said David W. Loring, PhD, Professor of Neurology and Pediatrics and Director of Neuropsychology in the Neurology Department at Emory University in Atlanta. “It is unclear if these effects are due to a direct positive effect on the stimulated structures or to modulatory reductions in the adverse effects of seizures or interictal discharges.”

Blinded and Open-Label Stimulation

Neurostimulation has been associated with declines in verbal fluency among patients with Parkinson’s disease, and with a decreased rate of cognitive decline among patients with Alzheimer’s disease. Patients with intractable partial seizures who received deep brain stimulation (DBS) complained of poorer memory and mood, although they had no evidence of neuropsychologic declines.

Dr. Loring and colleagues sought to determine the effect of long-term responsive neurostimulation on neuropsychologic performance among patients with epilepsy. The researchers examined data from a double-blind, randomized, sham-stimulation controlled study of the RNS System, which is manufactured by NeuroPace. Participants were between ages 18 and 66 and had an average of three or more simple partial motor, complex partial, or secondarily generalized tonic–clonic seizures per month. All participants had inadequate seizure control with at least two antiepileptic drugs (AEDs).

After a three-month baseline period, patients received implantation of the neurostimulator and leads. The device was programmed immediately to detect specific patterns of brain activity. One month after implantation, patients were randomized in groups of equal size to receive active or sham stimulation in response to detections. Participants were followed for four months before they received open-label responsive neurostimulation for 18 months.

The researchers collected neuropsychologic data at baseline and during the open-label period at one and two years after implantation. Primary neuropsychologic tests included the Boston Naming Test (BNT) and the Rey Auditory Verbal Learning Test (AVLT). Additional neuropsychologic domains were analyzed as secondary outcomes.

Seizure-Onset Zone Affected Outcomes

Data for 175 patients were analyzed. The study population’s average age was approximately 35, and 18% of participants were female. In all, 86 patients had seizure onset in the mesial temporal lobe, and 76 had seizure onset in the neocortex. Thirteen patients had seizure onset in both regions. They were included in analyses of all participants, but not in analyses according to seizure-onset zone.

Dr. Loring and colleagues observed no significant group performance decline on any neuropsychologic outcome measure. They did, however, find significant improvements on the BNT in 23.5% of participants. Approximately 7% of participants had declines on the BNT. The investigators also noted statistically significant improvements on the AVLT in 6.9% of patients. Approximately 1% of patients had declines on the AVLT. Dr. Loring and colleagues found a trend toward significant improvement on delayed AVLT recall, but no performance change for delayed AVLT recognition.

When the researchers analyzed the data according to seizure-onset zone, they found a significant improvement on the BNT among patients with neocortical seizure onsets. This improvement was not observed in participants with seizure onset in the mesial temporal lobe. In contrast, Dr. Loring’s group noted a significant overall improvement in AVLT learning in patients with seizure onset in the mesial temporal lobe, but not in patients with neocortical seizure onset. Adjusting the data for prior epilepsy surgery and for change in seizure frequency did not alter the results.

Improvements in naming and verbal memory are “an important observation, given the cognitive side effects of some AEDs and the presence of cognitive decline with DBS stimulation of the subthalamic nuclei or of the globus pallidus for Parkinson’s disease,” said Dr. Loring. “The double dissociation observed serves primarily to provide empirical evidence that neurostimulation techniques may ultimately provide therapeutic benefit, and to conceptually support future studies directed explicitly at establishing and optimizing neurostimulation parameters to enhance cognition.”

The fact that naming and verbal memory performance varied according to the seizure-onset region indicates that performance improvements were unlikely to be practice effects. “Practice effects are expected to occur at equal magnitudes in all clinical groups with comparable overall status,” said Dr. Loring. Nor did cognitive outcomes at two years appear to be associated with changes in AEDs.

“This series provides evidence that adults with frequent, intractable, partial onset seizures treated with responsive neurostimulation are not at increased risk for developing cognitive dysfunction, and that some aspects of cognition may be improved,” Dr. Loring concluded.

—Erik Greb

Among adult patients with medically refractory partial-onset seizures, treatment with responsive neurostimulation is not associated with cognitive decline over two years, according to data published in the November issue of Epilepsia. The therapy may in fact induce small but significant improvements in naming among patients with neocortical seizure onset and modest improvements in verbal learning among patients with seizure onset in the mesial temporal lobe.

“These findings require replication but suggest potential cognitive therapeutic benefit associated with responsive neurostimulation,” said David W. Loring, PhD, Professor of Neurology and Pediatrics and Director of Neuropsychology in the Neurology Department at Emory University in Atlanta. “It is unclear if these effects are due to a direct positive effect on the stimulated structures or to modulatory reductions in the adverse effects of seizures or interictal discharges.”

Blinded and Open-Label Stimulation

Neurostimulation has been associated with declines in verbal fluency among patients with Parkinson’s disease, and with a decreased rate of cognitive decline among patients with Alzheimer’s disease. Patients with intractable partial seizures who received deep brain stimulation (DBS) complained of poorer memory and mood, although they had no evidence of neuropsychologic declines.

Dr. Loring and colleagues sought to determine the effect of long-term responsive neurostimulation on neuropsychologic performance among patients with epilepsy. The researchers examined data from a double-blind, randomized, sham-stimulation controlled study of the RNS System, which is manufactured by NeuroPace. Participants were between ages 18 and 66 and had an average of three or more simple partial motor, complex partial, or secondarily generalized tonic–clonic seizures per month. All participants had inadequate seizure control with at least two antiepileptic drugs (AEDs).

After a three-month baseline period, patients received implantation of the neurostimulator and leads. The device was programmed immediately to detect specific patterns of brain activity. One month after implantation, patients were randomized in groups of equal size to receive active or sham stimulation in response to detections. Participants were followed for four months before they received open-label responsive neurostimulation for 18 months.

The researchers collected neuropsychologic data at baseline and during the open-label period at one and two years after implantation. Primary neuropsychologic tests included the Boston Naming Test (BNT) and the Rey Auditory Verbal Learning Test (AVLT). Additional neuropsychologic domains were analyzed as secondary outcomes.

Seizure-Onset Zone Affected Outcomes

Data for 175 patients were analyzed. The study population’s average age was approximately 35, and 18% of participants were female. In all, 86 patients had seizure onset in the mesial temporal lobe, and 76 had seizure onset in the neocortex. Thirteen patients had seizure onset in both regions. They were included in analyses of all participants, but not in analyses according to seizure-onset zone.

Dr. Loring and colleagues observed no significant group performance decline on any neuropsychologic outcome measure. They did, however, find significant improvements on the BNT in 23.5% of participants. Approximately 7% of participants had declines on the BNT. The investigators also noted statistically significant improvements on the AVLT in 6.9% of patients. Approximately 1% of patients had declines on the AVLT. Dr. Loring and colleagues found a trend toward significant improvement on delayed AVLT recall, but no performance change for delayed AVLT recognition.

When the researchers analyzed the data according to seizure-onset zone, they found a significant improvement on the BNT among patients with neocortical seizure onsets. This improvement was not observed in participants with seizure onset in the mesial temporal lobe. In contrast, Dr. Loring’s group noted a significant overall improvement in AVLT learning in patients with seizure onset in the mesial temporal lobe, but not in patients with neocortical seizure onset. Adjusting the data for prior epilepsy surgery and for change in seizure frequency did not alter the results.

Improvements in naming and verbal memory are “an important observation, given the cognitive side effects of some AEDs and the presence of cognitive decline with DBS stimulation of the subthalamic nuclei or of the globus pallidus for Parkinson’s disease,” said Dr. Loring. “The double dissociation observed serves primarily to provide empirical evidence that neurostimulation techniques may ultimately provide therapeutic benefit, and to conceptually support future studies directed explicitly at establishing and optimizing neurostimulation parameters to enhance cognition.”

The fact that naming and verbal memory performance varied according to the seizure-onset region indicates that performance improvements were unlikely to be practice effects. “Practice effects are expected to occur at equal magnitudes in all clinical groups with comparable overall status,” said Dr. Loring. Nor did cognitive outcomes at two years appear to be associated with changes in AEDs.

“This series provides evidence that adults with frequent, intractable, partial onset seizures treated with responsive neurostimulation are not at increased risk for developing cognitive dysfunction, and that some aspects of cognition may be improved,” Dr. Loring concluded.

—Erik Greb

Among adult patients with medically refractory partial-onset seizures, treatment with responsive neurostimulation is not associated with cognitive decline over two years, according to data published in the November issue of Epilepsia. The therapy may in fact induce small but significant improvements in naming among patients with neocortical seizure onset and modest improvements in verbal learning among patients with seizure onset in the mesial temporal lobe.

“These findings require replication but suggest potential cognitive therapeutic benefit associated with responsive neurostimulation,” said David W. Loring, PhD, Professor of Neurology and Pediatrics and Director of Neuropsychology in the Neurology Department at Emory University in Atlanta. “It is unclear if these effects are due to a direct positive effect on the stimulated structures or to modulatory reductions in the adverse effects of seizures or interictal discharges.”

Blinded and Open-Label Stimulation

Neurostimulation has been associated with declines in verbal fluency among patients with Parkinson’s disease, and with a decreased rate of cognitive decline among patients with Alzheimer’s disease. Patients with intractable partial seizures who received deep brain stimulation (DBS) complained of poorer memory and mood, although they had no evidence of neuropsychologic declines.

Dr. Loring and colleagues sought to determine the effect of long-term responsive neurostimulation on neuropsychologic performance among patients with epilepsy. The researchers examined data from a double-blind, randomized, sham-stimulation controlled study of the RNS System, which is manufactured by NeuroPace. Participants were between ages 18 and 66 and had an average of three or more simple partial motor, complex partial, or secondarily generalized tonic–clonic seizures per month. All participants had inadequate seizure control with at least two antiepileptic drugs (AEDs).

After a three-month baseline period, patients received implantation of the neurostimulator and leads. The device was programmed immediately to detect specific patterns of brain activity. One month after implantation, patients were randomized in groups of equal size to receive active or sham stimulation in response to detections. Participants were followed for four months before they received open-label responsive neurostimulation for 18 months.

The researchers collected neuropsychologic data at baseline and during the open-label period at one and two years after implantation. Primary neuropsychologic tests included the Boston Naming Test (BNT) and the Rey Auditory Verbal Learning Test (AVLT). Additional neuropsychologic domains were analyzed as secondary outcomes.

Seizure-Onset Zone Affected Outcomes

Data for 175 patients were analyzed. The study population’s average age was approximately 35, and 18% of participants were female. In all, 86 patients had seizure onset in the mesial temporal lobe, and 76 had seizure onset in the neocortex. Thirteen patients had seizure onset in both regions. They were included in analyses of all participants, but not in analyses according to seizure-onset zone.

Dr. Loring and colleagues observed no significant group performance decline on any neuropsychologic outcome measure. They did, however, find significant improvements on the BNT in 23.5% of participants. Approximately 7% of participants had declines on the BNT. The investigators also noted statistically significant improvements on the AVLT in 6.9% of patients. Approximately 1% of patients had declines on the AVLT. Dr. Loring and colleagues found a trend toward significant improvement on delayed AVLT recall, but no performance change for delayed AVLT recognition.

When the researchers analyzed the data according to seizure-onset zone, they found a significant improvement on the BNT among patients with neocortical seizure onsets. This improvement was not observed in participants with seizure onset in the mesial temporal lobe. In contrast, Dr. Loring’s group noted a significant overall improvement in AVLT learning in patients with seizure onset in the mesial temporal lobe, but not in patients with neocortical seizure onset. Adjusting the data for prior epilepsy surgery and for change in seizure frequency did not alter the results.

Improvements in naming and verbal memory are “an important observation, given the cognitive side effects of some AEDs and the presence of cognitive decline with DBS stimulation of the subthalamic nuclei or of the globus pallidus for Parkinson’s disease,” said Dr. Loring. “The double dissociation observed serves primarily to provide empirical evidence that neurostimulation techniques may ultimately provide therapeutic benefit, and to conceptually support future studies directed explicitly at establishing and optimizing neurostimulation parameters to enhance cognition.”

The fact that naming and verbal memory performance varied according to the seizure-onset region indicates that performance improvements were unlikely to be practice effects. “Practice effects are expected to occur at equal magnitudes in all clinical groups with comparable overall status,” said Dr. Loring. Nor did cognitive outcomes at two years appear to be associated with changes in AEDs.

“This series provides evidence that adults with frequent, intractable, partial onset seizures treated with responsive neurostimulation are not at increased risk for developing cognitive dysfunction, and that some aspects of cognition may be improved,” Dr. Loring concluded.

—Erik Greb

Researchers examined records of 176 patients (45 with and 131 without invasive EEG) who underwent left temporal lobe resection (TLR) at Cleveland Clinic. There were no clinically meaningful changes in naming performance or verbal memory. Patients with invasive monitoring showed greater declines in working memory, which were no longer apparent using reliable change indices to define change. Overall results suggest that invasive EEG monitoring prior to left TLR is not associated with greater cognitive morbidity.

Busch RM, Love TE, Jehi LE, et al. Effect of invasive EEG monitoring on cognitive outcome after left temporal lobe epilepsy surgery.  Neurology. 2015;85(17):1475-1481.

Researchers examined records of 176 patients (45 with and 131 without invasive EEG) who underwent left temporal lobe resection (TLR) at Cleveland Clinic. There were no clinically meaningful changes in naming performance or verbal memory. Patients with invasive monitoring showed greater declines in working memory, which were no longer apparent using reliable change indices to define change. Overall results suggest that invasive EEG monitoring prior to left TLR is not associated with greater cognitive morbidity.

Busch RM, Love TE, Jehi LE, et al. Effect of invasive EEG monitoring on cognitive outcome after left temporal lobe epilepsy surgery.  Neurology. 2015;85(17):1475-1481.

Researchers examined records of 176 patients (45 with and 131 without invasive EEG) who underwent left temporal lobe resection (TLR) at Cleveland Clinic. There were no clinically meaningful changes in naming performance or verbal memory. Patients with invasive monitoring showed greater declines in working memory, which were no longer apparent using reliable change indices to define change. Overall results suggest that invasive EEG monitoring prior to left TLR is not associated with greater cognitive morbidity.

Busch RM, Love TE, Jehi LE, et al. Effect of invasive EEG monitoring on cognitive outcome after left temporal lobe epilepsy surgery.  Neurology. 2015;85(17):1475-1481.

This meta-analysis examined 16 studies of nonvenous drugs used in randomized controlled trials for the treatment of acute convulsive seizures and convulsive status epilepticus. Intramuscular midazolam was superior to other nonvenous medications for time to seizure termination after administration, time to seizure cessation after arrival at the hospital, and the time to initiate treatment. Intranasal midazolam was found most effective for seizure cessation within 10 minutes of administration.

Arya R, Kothari H, Zhang Z, Han B, Horn PS, Glauser TA. Efficacy of nonvenous medications for acute convulsive seizures: a network meta-analysis. Neurology 2015: doi: 10.1212/WNL.0000000000002142.

This meta-analysis examined 16 studies of nonvenous drugs used in randomized controlled trials for the treatment of acute convulsive seizures and convulsive status epilepticus. Intramuscular midazolam was superior to other nonvenous medications for time to seizure termination after administration, time to seizure cessation after arrival at the hospital, and the time to initiate treatment. Intranasal midazolam was found most effective for seizure cessation within 10 minutes of administration.

Arya R, Kothari H, Zhang Z, Han B, Horn PS, Glauser TA. Efficacy of nonvenous medications for acute convulsive seizures: a network meta-analysis. Neurology 2015: doi: 10.1212/WNL.0000000000002142.

This meta-analysis examined 16 studies of nonvenous drugs used in randomized controlled trials for the treatment of acute convulsive seizures and convulsive status epilepticus. Intramuscular midazolam was superior to other nonvenous medications for time to seizure termination after administration, time to seizure cessation after arrival at the hospital, and the time to initiate treatment. Intranasal midazolam was found most effective for seizure cessation within 10 minutes of administration.

Arya R, Kothari H, Zhang Z, Han B, Horn PS, Glauser TA. Efficacy of nonvenous medications for acute convulsive seizures: a network meta-analysis. Neurology 2015: doi: 10.1212/WNL.0000000000002142.

In this study, researchers surveyed 90 patients with intractable epilepsy who underwent vagus nerve stimulation (VNS). This is the first study to assess both seizure and psychosocial outcomes in this population. The authors found no significant differences in psychosocial metrics before and after VNS implantation. Seizure outcomes were favorable with 68% of patients experience greater than 50% seizure reduction and 20% of patients identifying as seizure-free. The majority of patients surveyed (80%) expressed satisfaction with VNS therapy.

Wasade VS, Schultz L, Mohanarangan K, Gaddam A, Schwalb JM, Spanaki-Varelas M. Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy. Epilepsy Behav. 2015;53:31-36.

In this study, researchers surveyed 90 patients with intractable epilepsy who underwent vagus nerve stimulation (VNS). This is the first study to assess both seizure and psychosocial outcomes in this population. The authors found no significant differences in psychosocial metrics before and after VNS implantation. Seizure outcomes were favorable with 68% of patients experience greater than 50% seizure reduction and 20% of patients identifying as seizure-free. The majority of patients surveyed (80%) expressed satisfaction with VNS therapy.

Wasade VS, Schultz L, Mohanarangan K, Gaddam A, Schwalb JM, Spanaki-Varelas M. Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy. Epilepsy Behav. 2015;53:31-36.

In this study, researchers surveyed 90 patients with intractable epilepsy who underwent vagus nerve stimulation (VNS). This is the first study to assess both seizure and psychosocial outcomes in this population. The authors found no significant differences in psychosocial metrics before and after VNS implantation. Seizure outcomes were favorable with 68% of patients experience greater than 50% seizure reduction and 20% of patients identifying as seizure-free. The majority of patients surveyed (80%) expressed satisfaction with VNS therapy.

Wasade VS, Schultz L, Mohanarangan K, Gaddam A, Schwalb JM, Spanaki-Varelas M. Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy. Epilepsy Behav. 2015;53:31-36.

In this study, researchers surveyed 90 patients with intractable epilepsy who underwent vagus nerve stimulation (VNS). This is the first study to assess both seizure and psychosocial outcomes in this population. The authors found no significant differences in psychosocial metrics before and after VNS implantation. Seizure outcomes were favorable with 68% of patients experience greater than 50% seizure reduction and 20% of patients identifying as seizure-free. The majority of patients surveyed (80%) expressed satisfaction with VNS therapy.

Wasade VS, Schultz L, Mohanarangan K, Gaddam A, Schwalb JM, Spanaki-Varelas M. Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy. Epilepsy Behav. 2015;53:31-36.

In this study, researchers surveyed 90 patients with intractable epilepsy who underwent vagus nerve stimulation (VNS). This is the first study to assess both seizure and psychosocial outcomes in this population. The authors found no significant differences in psychosocial metrics before and after VNS implantation. Seizure outcomes were favorable with 68% of patients experience greater than 50% seizure reduction and 20% of patients identifying as seizure-free. The majority of patients surveyed (80%) expressed satisfaction with VNS therapy.

Wasade VS, Schultz L, Mohanarangan K, Gaddam A, Schwalb JM, Spanaki-Varelas M. Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy. Epilepsy Behav. 2015;53:31-36.

In this study, researchers surveyed 90 patients with intractable epilepsy who underwent vagus nerve stimulation (VNS). This is the first study to assess both seizure and psychosocial outcomes in this population. The authors found no significant differences in psychosocial metrics before and after VNS implantation. Seizure outcomes were favorable with 68% of patients experience greater than 50% seizure reduction and 20% of patients identifying as seizure-free. The majority of patients surveyed (80%) expressed satisfaction with VNS therapy.

Wasade VS, Schultz L, Mohanarangan K, Gaddam A, Schwalb JM, Spanaki-Varelas M. Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy. Epilepsy Behav. 2015;53:31-36.

If a genetic disorder is suspected as the cause of treatment-resistant epilepsy, appropriate genetic tests may lead to timely diagnosis and targeted therapy, as well as reduce overall costs and limit anxiety to families, said Anup Patel, MD, in a review paper published online ahead of print September 8 in Epilepsia. In a literature review, Dr. Patel and Margie A. Ream, MD, PhD, discussed the genetic methods available, along with their advantages and disadvantages.

“Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors unless the ordering neurologist has a strong background in and understanding of genetics,” the authors advised. Drs. Ream and Patel are Assistant Professors in the Department of Pediatrics at Nationwide Children’s Hospital and Ohio State University in Columbus.

Generally, genetic testing is not recommended for patients with drug-responsive epilepsy or at epilepsy onset, although comparative genomic hybridization can be useful at first evaluation of a patient with global developmental delay. Metabolic testing should be undertaken at the onset of epilepsy in infants without a structural or syndromic cause of their seizures.

For children with drug-resistant epilepsy, Drs. Ream and Patel proposed a diagnosis algorithm. Biochemical testing should be the first line of action to uncover treatable metabolic disorders such as inborn errors of metabolism, which often cause seizures. Metabolic testing gives quicker results than targeted genetic studies or gene panels, thus allowing for more rapid treatment initiation. In most cases, there are several phenotypic variations of genetic epilepsy, and many genes would need to be tested for a given phenotype. This situation often makes targeted gene sequencing costlier than a gene panel.

Drug-resistant epilepsy, especially when associated with developmental delay or congenital anomalies, should prompt comparative genomic hybridization analysis, which detects copy number variations (ie, DNA deletions or duplications). The analysis’s sensitivity of 23.5% increases when multiple abnormalities are present. Aneuploidy and balanced translocations not detectable by comparative genomic hybridization can be found with karyotype.

The next test in the algorithm is a gene panel. This broad genetic test is useful in identifying specific genes and may be the most cost-effective way to approach diagnosing a broad phenotype.

Beyond gene panel testing, an even broader genetic evaluation is whole exome sequencing. This method tests all exons in the genome, is not limited to known epilepsy genes, and has 39% sensitivity. Whole exome sequencing is indicated in genetically heterogeneous disorders, when there is a suspected genetic disease lacking a specific test, when other genetic tests are negative for suspected disorders, and, in some cases, for prenatal testing. The disadvantage of whole exome sequencing is that it results in complex data, but it holds the potential for gene discovery in patients with similar phenotypes or if gene mutations occur in a common biochemical pathway. Whole exome sequencing costs in the range of $5,000 to $14,000 but sometimes can be less costly than traditional molecular diagnostic approaches.

Drs. Ream and Patel recommended “reserving whole exome sequencing for the most elusive cases” until it becomes more cost-effective. Ideally, they said, in the future, “whole exome sequencing could be tailored for epilepsy patients by optimizing coverage of known epilepsy genes.”

—Evelyn Tran

If a genetic disorder is suspected as the cause of treatment-resistant epilepsy, appropriate genetic tests may lead to timely diagnosis and targeted therapy, as well as reduce overall costs and limit anxiety to families, said Anup Patel, MD, in a review paper published online ahead of print September 8 in Epilepsia. In a literature review, Dr. Patel and Margie A. Ream, MD, PhD, discussed the genetic methods available, along with their advantages and disadvantages.

“Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors unless the ordering neurologist has a strong background in and understanding of genetics,” the authors advised. Drs. Ream and Patel are Assistant Professors in the Department of Pediatrics at Nationwide Children’s Hospital and Ohio State University in Columbus.

Generally, genetic testing is not recommended for patients with drug-responsive epilepsy or at epilepsy onset, although comparative genomic hybridization can be useful at first evaluation of a patient with global developmental delay. Metabolic testing should be undertaken at the onset of epilepsy in infants without a structural or syndromic cause of their seizures.

For children with drug-resistant epilepsy, Drs. Ream and Patel proposed a diagnosis algorithm. Biochemical testing should be the first line of action to uncover treatable metabolic disorders such as inborn errors of metabolism, which often cause seizures. Metabolic testing gives quicker results than targeted genetic studies or gene panels, thus allowing for more rapid treatment initiation. In most cases, there are several phenotypic variations of genetic epilepsy, and many genes would need to be tested for a given phenotype. This situation often makes targeted gene sequencing costlier than a gene panel.

Drug-resistant epilepsy, especially when associated with developmental delay or congenital anomalies, should prompt comparative genomic hybridization analysis, which detects copy number variations (ie, DNA deletions or duplications). The analysis’s sensitivity of 23.5% increases when multiple abnormalities are present. Aneuploidy and balanced translocations not detectable by comparative genomic hybridization can be found with karyotype.

The next test in the algorithm is a gene panel. This broad genetic test is useful in identifying specific genes and may be the most cost-effective way to approach diagnosing a broad phenotype.

Beyond gene panel testing, an even broader genetic evaluation is whole exome sequencing. This method tests all exons in the genome, is not limited to known epilepsy genes, and has 39% sensitivity. Whole exome sequencing is indicated in genetically heterogeneous disorders, when there is a suspected genetic disease lacking a specific test, when other genetic tests are negative for suspected disorders, and, in some cases, for prenatal testing. The disadvantage of whole exome sequencing is that it results in complex data, but it holds the potential for gene discovery in patients with similar phenotypes or if gene mutations occur in a common biochemical pathway. Whole exome sequencing costs in the range of $5,000 to $14,000 but sometimes can be less costly than traditional molecular diagnostic approaches.

Drs. Ream and Patel recommended “reserving whole exome sequencing for the most elusive cases” until it becomes more cost-effective. Ideally, they said, in the future, “whole exome sequencing could be tailored for epilepsy patients by optimizing coverage of known epilepsy genes.”

—Evelyn Tran

If a genetic disorder is suspected as the cause of treatment-resistant epilepsy, appropriate genetic tests may lead to timely diagnosis and targeted therapy, as well as reduce overall costs and limit anxiety to families, said Anup Patel, MD, in a review paper published online ahead of print September 8 in Epilepsia. In a literature review, Dr. Patel and Margie A. Ream, MD, PhD, discussed the genetic methods available, along with their advantages and disadvantages.

“Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors unless the ordering neurologist has a strong background in and understanding of genetics,” the authors advised. Drs. Ream and Patel are Assistant Professors in the Department of Pediatrics at Nationwide Children’s Hospital and Ohio State University in Columbus.

Generally, genetic testing is not recommended for patients with drug-responsive epilepsy or at epilepsy onset, although comparative genomic hybridization can be useful at first evaluation of a patient with global developmental delay. Metabolic testing should be undertaken at the onset of epilepsy in infants without a structural or syndromic cause of their seizures.

For children with drug-resistant epilepsy, Drs. Ream and Patel proposed a diagnosis algorithm. Biochemical testing should be the first line of action to uncover treatable metabolic disorders such as inborn errors of metabolism, which often cause seizures. Metabolic testing gives quicker results than targeted genetic studies or gene panels, thus allowing for more rapid treatment initiation. In most cases, there are several phenotypic variations of genetic epilepsy, and many genes would need to be tested for a given phenotype. This situation often makes targeted gene sequencing costlier than a gene panel.

Drug-resistant epilepsy, especially when associated with developmental delay or congenital anomalies, should prompt comparative genomic hybridization analysis, which detects copy number variations (ie, DNA deletions or duplications). The analysis’s sensitivity of 23.5% increases when multiple abnormalities are present. Aneuploidy and balanced translocations not detectable by comparative genomic hybridization can be found with karyotype.

The next test in the algorithm is a gene panel. This broad genetic test is useful in identifying specific genes and may be the most cost-effective way to approach diagnosing a broad phenotype.

Beyond gene panel testing, an even broader genetic evaluation is whole exome sequencing. This method tests all exons in the genome, is not limited to known epilepsy genes, and has 39% sensitivity. Whole exome sequencing is indicated in genetically heterogeneous disorders, when there is a suspected genetic disease lacking a specific test, when other genetic tests are negative for suspected disorders, and, in some cases, for prenatal testing. The disadvantage of whole exome sequencing is that it results in complex data, but it holds the potential for gene discovery in patients with similar phenotypes or if gene mutations occur in a common biochemical pathway. Whole exome sequencing costs in the range of $5,000 to $14,000 but sometimes can be less costly than traditional molecular diagnostic approaches.

Drs. Ream and Patel recommended “reserving whole exome sequencing for the most elusive cases” until it becomes more cost-effective. Ideally, they said, in the future, “whole exome sequencing could be tailored for epilepsy patients by optimizing coverage of known epilepsy genes.”

—Evelyn Tran

Perampanel, when used as adjunctive therapy in the treatment of drug-resistant primary generalized tonic-clonic seizures in patients 12 and older, reduced median seizure frequency, compared with placebo, according to the results of a phase III trial published online ahead of print August 21 in Neurology. Results of the multicenter, randomized, double-blind, placebo-controlled clinical trial of 162 patients who were taking one to three antiepileptic drugs showed that patients taking perampanel achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency per 28 days. This result was statistically significant when compared with a 38% reduction with placebo. Additionally, 64% of patients taking perampanel experienced a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo.

“These data showed a significant median reduction in the frequency of primary generalized tonic-clonic seizures in patients that had [perampanel] added to their treatment regimen,” said lead author Jacqueline A. French, MD, Professor at New York University Comprehensive Epilepsy Center and Chief Science Officer of the Epilepsy Foundation. “As the number of treatment options are limited for patients with primary generalized tonic-clonic seizures, [perampanel] may provide a new option for this group.”

Dr. French and colleagues enrolled patients age 12 or older with primary generalized tonic-clonic seizures and idiopathic generalized epilepsy. Study participants were randomized to placebo or perampanel during a four-week titration period. During this period, perampanel was titrated from 2 to 8 mg/day or to the highest tolerated dose. The titration period was followed by a 13-week maintenance period.

The primary end point was percent change in seizure frequency per 28 days. The secondary end point was 50% primary generalized tonic-clonic seizure responder rate, which was defined as patients achieving a 50% or greater reduction in seizure frequency.

The full analysis set included 162 patients. The control and treatment groups each had 81 patients. Compared with placebo, perampanel conferred a greater median percent change in primary generalized tonic-clonic seizure frequency per 28 days (-38.4% for placebo vs -76.5% for perampanel). The 50% seizure responder rate was 39.5% for placebo and 64.2% for perampanel. During the maintenance period, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved seizure freedom. The most frequently reported treatment-emergent adverse events were dizziness (32.1%) and fatigue (14.8%).

The authors concluded that “this study provides Class I evidence that adjunctive perampanel reduces primary generalized tonic-clonic seizure frequency, compared with placebo, in patients with drug-resistant primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.”

—Glenn S. Williams

Perampanel, when used as adjunctive therapy in the treatment of drug-resistant primary generalized tonic-clonic seizures in patients 12 and older, reduced median seizure frequency, compared with placebo, according to the results of a phase III trial published online ahead of print August 21 in Neurology. Results of the multicenter, randomized, double-blind, placebo-controlled clinical trial of 162 patients who were taking one to three antiepileptic drugs showed that patients taking perampanel achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency per 28 days. This result was statistically significant when compared with a 38% reduction with placebo. Additionally, 64% of patients taking perampanel experienced a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo.

“These data showed a significant median reduction in the frequency of primary generalized tonic-clonic seizures in patients that had [perampanel] added to their treatment regimen,” said lead author Jacqueline A. French, MD, Professor at New York University Comprehensive Epilepsy Center and Chief Science Officer of the Epilepsy Foundation. “As the number of treatment options are limited for patients with primary generalized tonic-clonic seizures, [perampanel] may provide a new option for this group.”

Dr. French and colleagues enrolled patients age 12 or older with primary generalized tonic-clonic seizures and idiopathic generalized epilepsy. Study participants were randomized to placebo or perampanel during a four-week titration period. During this period, perampanel was titrated from 2 to 8 mg/day or to the highest tolerated dose. The titration period was followed by a 13-week maintenance period.

The primary end point was percent change in seizure frequency per 28 days. The secondary end point was 50% primary generalized tonic-clonic seizure responder rate, which was defined as patients achieving a 50% or greater reduction in seizure frequency.

The full analysis set included 162 patients. The control and treatment groups each had 81 patients. Compared with placebo, perampanel conferred a greater median percent change in primary generalized tonic-clonic seizure frequency per 28 days (-38.4% for placebo vs -76.5% for perampanel). The 50% seizure responder rate was 39.5% for placebo and 64.2% for perampanel. During the maintenance period, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved seizure freedom. The most frequently reported treatment-emergent adverse events were dizziness (32.1%) and fatigue (14.8%).

The authors concluded that “this study provides Class I evidence that adjunctive perampanel reduces primary generalized tonic-clonic seizure frequency, compared with placebo, in patients with drug-resistant primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.”

—Glenn S. Williams

Perampanel, when used as adjunctive therapy in the treatment of drug-resistant primary generalized tonic-clonic seizures in patients 12 and older, reduced median seizure frequency, compared with placebo, according to the results of a phase III trial published online ahead of print August 21 in Neurology. Results of the multicenter, randomized, double-blind, placebo-controlled clinical trial of 162 patients who were taking one to three antiepileptic drugs showed that patients taking perampanel achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency per 28 days. This result was statistically significant when compared with a 38% reduction with placebo. Additionally, 64% of patients taking perampanel experienced a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo.

“These data showed a significant median reduction in the frequency of primary generalized tonic-clonic seizures in patients that had [perampanel] added to their treatment regimen,” said lead author Jacqueline A. French, MD, Professor at New York University Comprehensive Epilepsy Center and Chief Science Officer of the Epilepsy Foundation. “As the number of treatment options are limited for patients with primary generalized tonic-clonic seizures, [perampanel] may provide a new option for this group.”

Dr. French and colleagues enrolled patients age 12 or older with primary generalized tonic-clonic seizures and idiopathic generalized epilepsy. Study participants were randomized to placebo or perampanel during a four-week titration period. During this period, perampanel was titrated from 2 to 8 mg/day or to the highest tolerated dose. The titration period was followed by a 13-week maintenance period.

The primary end point was percent change in seizure frequency per 28 days. The secondary end point was 50% primary generalized tonic-clonic seizure responder rate, which was defined as patients achieving a 50% or greater reduction in seizure frequency.

The full analysis set included 162 patients. The control and treatment groups each had 81 patients. Compared with placebo, perampanel conferred a greater median percent change in primary generalized tonic-clonic seizure frequency per 28 days (-38.4% for placebo vs -76.5% for perampanel). The 50% seizure responder rate was 39.5% for placebo and 64.2% for perampanel. During the maintenance period, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved seizure freedom. The most frequently reported treatment-emergent adverse events were dizziness (32.1%) and fatigue (14.8%).

The authors concluded that “this study provides Class I evidence that adjunctive perampanel reduces primary generalized tonic-clonic seizure frequency, compared with placebo, in patients with drug-resistant primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.”

—Glenn S. Williams