Epilepsy Resource Center

About 50% of patients with epilepsy remained untreated for 6 months after their initial diagnosis according to a retrospective analysis of more than 58,000 cases.

• At 6 months after diagnosis, 46.8% were receiving treatment with antiepilepsy medication; at 12 months, that statistic had only climbed to 52.2%.
• Among the 29,226 patients who were receiving medication, nearly three quarters received monotherapy and 1.6% polytherapy as first treatment for 90 days or longer.
• The likelihood of patients remaining on antiepilepsy medication after a year was 61% for those on a single agent and 36.5% for those on more than one drug.

Faught E, Helmers S, Thurman D, et al. Patient characteristics and treatment patterns in patients with newly diagnosed epilepsy: A US database analysis. Epilepsy Behav. 2018;85:37-44.

About 50% of patients with epilepsy remained untreated for 6 months after their initial diagnosis according to a retrospective analysis of more than 58,000 cases.

• At 6 months after diagnosis, 46.8% were receiving treatment with antiepilepsy medication; at 12 months, that statistic had only climbed to 52.2%.
• Among the 29,226 patients who were receiving medication, nearly three quarters received monotherapy and 1.6% polytherapy as first treatment for 90 days or longer.
• The likelihood of patients remaining on antiepilepsy medication after a year was 61% for those on a single agent and 36.5% for those on more than one drug.

Faught E, Helmers S, Thurman D, et al. Patient characteristics and treatment patterns in patients with newly diagnosed epilepsy: A US database analysis. Epilepsy Behav. 2018;85:37-44.

About 50% of patients with epilepsy remained untreated for 6 months after their initial diagnosis according to a retrospective analysis of more than 58,000 cases.

• At 6 months after diagnosis, 46.8% were receiving treatment with antiepilepsy medication; at 12 months, that statistic had only climbed to 52.2%.
• Among the 29,226 patients who were receiving medication, nearly three quarters received monotherapy and 1.6% polytherapy as first treatment for 90 days or longer.
• The likelihood of patients remaining on antiepilepsy medication after a year was 61% for those on a single agent and 36.5% for those on more than one drug.

Faught E, Helmers S, Thurman D, et al. Patient characteristics and treatment patterns in patients with newly diagnosed epilepsy: A US database analysis. Epilepsy Behav. 2018;85:37-44.

Nearly half of patients with epilepsy have symptoms of high anxiety according to a study of adults treated in tertiary care centers.

• The study, which included 540 patients, evaluated the presence of anxiety with the Symptoms Checklist 90-R anxiety subscale. It also evaluated patients for depression with separate scales.
• 250 patients (46.1%) reported high anxiety.
• Focal epilepsy and epilepsy of unknown type, as well as depression scores, were independently linked to high anxiety.
• In patients with focal epilepsy, mesial temporal sclerosis was independently associated with high anxiety.
• Other factors linked to high anxiety included lower education level, being non-white, having Spanish as a native language, prior head trauma, and polydrug therapy for epilepsy.
• The researchers suggest that screening for anxiety in an epilepsy clinic can help spot patients in need of treatment.

Munger Clary HM, Snively BM, Hamberger MJ. Anxiety is common and independently associated with clinical features of epilepsy. Epilepsy Behav. 2018;85:64-71.

Nearly half of patients with epilepsy have symptoms of high anxiety according to a study of adults treated in tertiary care centers.

• The study, which included 540 patients, evaluated the presence of anxiety with the Symptoms Checklist 90-R anxiety subscale. It also evaluated patients for depression with separate scales.
• 250 patients (46.1%) reported high anxiety.
• Focal epilepsy and epilepsy of unknown type, as well as depression scores, were independently linked to high anxiety.
• In patients with focal epilepsy, mesial temporal sclerosis was independently associated with high anxiety.
• Other factors linked to high anxiety included lower education level, being non-white, having Spanish as a native language, prior head trauma, and polydrug therapy for epilepsy.
• The researchers suggest that screening for anxiety in an epilepsy clinic can help spot patients in need of treatment.

Munger Clary HM, Snively BM, Hamberger MJ. Anxiety is common and independently associated with clinical features of epilepsy. Epilepsy Behav. 2018;85:64-71.

Nearly half of patients with epilepsy have symptoms of high anxiety according to a study of adults treated in tertiary care centers.

• The study, which included 540 patients, evaluated the presence of anxiety with the Symptoms Checklist 90-R anxiety subscale. It also evaluated patients for depression with separate scales.
• 250 patients (46.1%) reported high anxiety.
• Focal epilepsy and epilepsy of unknown type, as well as depression scores, were independently linked to high anxiety.
• In patients with focal epilepsy, mesial temporal sclerosis was independently associated with high anxiety.
• Other factors linked to high anxiety included lower education level, being non-white, having Spanish as a native language, prior head trauma, and polydrug therapy for epilepsy.
• The researchers suggest that screening for anxiety in an epilepsy clinic can help spot patients in need of treatment.

Munger Clary HM, Snively BM, Hamberger MJ. Anxiety is common and independently associated with clinical features of epilepsy. Epilepsy Behav. 2018;85:64-71.

LOS ANGELES—Adjunctive treatment with an investigational antiepileptic drug (AED) reduces the median frequency of partial-onset seizures, according to trial results presented at the 70th Annual Meeting of the American Academy of Neurology.

“The results with cenobamate demonstrated a decrease in overall median seizure frequencies compared to placebo at all doses studied,” said study principal investigator Gregory Krauss, MD, Professor of Neurology at Johns Hopkins University in Baltimore.

Seizure Types

In all, 437 patients received 100 mg per day of cenobamate (n = 108), 200 mg per day of cenobamate (n = 110), 400 mg per day of cenobamate (n = 111), or placebo (n = 108). Patients’ average age was about 40, and patients had a median seizure frequency of between 8.4 and 11 seizures per month. Most patients had a history of complex partial seizures (78.9%) or secondary generalized tonic-clonic seizures (60.0%) and were receiving two or three concomitant AEDs.

Median seizure frequencies decreased for all doses of cenobamate (100 mg/day: 35.5%, 200 mg/day: 55.0%, and 400 mg/day: 55.0%), compared with placebo (24.0%). Median frequencies for simple partial seizures decreased with all doses of cenobamate (100 mg/day: 48.0%; 200 mg/day: 63.0%; and 400 mg/day: 58.5%), compared with placebo (7.0%). Median frequencies for complex partial seizures and secondary generalized tonic-clonic seizures decreased with 200 mg per day of cenobamate (55.0% and 91.0%, respectively) and 400 mg per day of cenobamate (60.0% and 78.0%, respectively), compared with placebo (28.5% and 33.0%, respectively).

Compared with patients who received placebo, patients who received cenobamate were more likely to have greater than 50% reductions and 100% reductions in seizure frequency, Dr. Krauss said.

Investigators Adjusted Titration

The most common adverse events were somnolence, dizziness, headache, and balance disorder. The percentage of patients with common adverse events increased with dose, and slightly more patients who received 400 mg per day of cenobamate dropped out of the trial, compared with patients who received lower doses, Dr. Krauss said. Some patients with adverse events in the 400 mg group required modest dose reductions, and some adverse events were related to titration, he said.

Two allergic reactions occurred during initial rapid titration of the drug. After rapid dose titration for the first 10% of patients in the trial, doses for the remaining patients were titrated more slowly. One patient in the fast titration group developed drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Two patients in the trial had the common morbilliform rash without systemic signs—one during fast titration and one during slower titration.

Most adverse events were mild to moderate, and there were no deaths. In all, 37 adverse events occurred in 28 patients, and the number of adverse events was comparable between placebo and cenobamate, Dr. Krauss said. The most common serious adverse events were seizures in four patients, ataxias in two patients, dizziness in two patients, nystagmus in two patients, and suicidal ideation in two patients.

SK Life Science, based in Fair Lawn, New Jersey, is developing cenobamate.

—Jake Remaly

LOS ANGELES—Adjunctive treatment with an investigational antiepileptic drug (AED) reduces the median frequency of partial-onset seizures, according to trial results presented at the 70th Annual Meeting of the American Academy of Neurology.

“The results with cenobamate demonstrated a decrease in overall median seizure frequencies compared to placebo at all doses studied,” said study principal investigator Gregory Krauss, MD, Professor of Neurology at Johns Hopkins University in Baltimore.

Seizure Types

In all, 437 patients received 100 mg per day of cenobamate (n = 108), 200 mg per day of cenobamate (n = 110), 400 mg per day of cenobamate (n = 111), or placebo (n = 108). Patients’ average age was about 40, and patients had a median seizure frequency of between 8.4 and 11 seizures per month. Most patients had a history of complex partial seizures (78.9%) or secondary generalized tonic-clonic seizures (60.0%) and were receiving two or three concomitant AEDs.

Median seizure frequencies decreased for all doses of cenobamate (100 mg/day: 35.5%, 200 mg/day: 55.0%, and 400 mg/day: 55.0%), compared with placebo (24.0%). Median frequencies for simple partial seizures decreased with all doses of cenobamate (100 mg/day: 48.0%; 200 mg/day: 63.0%; and 400 mg/day: 58.5%), compared with placebo (7.0%). Median frequencies for complex partial seizures and secondary generalized tonic-clonic seizures decreased with 200 mg per day of cenobamate (55.0% and 91.0%, respectively) and 400 mg per day of cenobamate (60.0% and 78.0%, respectively), compared with placebo (28.5% and 33.0%, respectively).

Compared with patients who received placebo, patients who received cenobamate were more likely to have greater than 50% reductions and 100% reductions in seizure frequency, Dr. Krauss said.

Investigators Adjusted Titration

The most common adverse events were somnolence, dizziness, headache, and balance disorder. The percentage of patients with common adverse events increased with dose, and slightly more patients who received 400 mg per day of cenobamate dropped out of the trial, compared with patients who received lower doses, Dr. Krauss said. Some patients with adverse events in the 400 mg group required modest dose reductions, and some adverse events were related to titration, he said.

Two allergic reactions occurred during initial rapid titration of the drug. After rapid dose titration for the first 10% of patients in the trial, doses for the remaining patients were titrated more slowly. One patient in the fast titration group developed drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Two patients in the trial had the common morbilliform rash without systemic signs—one during fast titration and one during slower titration.

Most adverse events were mild to moderate, and there were no deaths. In all, 37 adverse events occurred in 28 patients, and the number of adverse events was comparable between placebo and cenobamate, Dr. Krauss said. The most common serious adverse events were seizures in four patients, ataxias in two patients, dizziness in two patients, nystagmus in two patients, and suicidal ideation in two patients.

SK Life Science, based in Fair Lawn, New Jersey, is developing cenobamate.

—Jake Remaly

LOS ANGELES—Adjunctive treatment with an investigational antiepileptic drug (AED) reduces the median frequency of partial-onset seizures, according to trial results presented at the 70th Annual Meeting of the American Academy of Neurology.

“The results with cenobamate demonstrated a decrease in overall median seizure frequencies compared to placebo at all doses studied,” said study principal investigator Gregory Krauss, MD, Professor of Neurology at Johns Hopkins University in Baltimore.

Seizure Types

In all, 437 patients received 100 mg per day of cenobamate (n = 108), 200 mg per day of cenobamate (n = 110), 400 mg per day of cenobamate (n = 111), or placebo (n = 108). Patients’ average age was about 40, and patients had a median seizure frequency of between 8.4 and 11 seizures per month. Most patients had a history of complex partial seizures (78.9%) or secondary generalized tonic-clonic seizures (60.0%) and were receiving two or three concomitant AEDs.

Median seizure frequencies decreased for all doses of cenobamate (100 mg/day: 35.5%, 200 mg/day: 55.0%, and 400 mg/day: 55.0%), compared with placebo (24.0%). Median frequencies for simple partial seizures decreased with all doses of cenobamate (100 mg/day: 48.0%; 200 mg/day: 63.0%; and 400 mg/day: 58.5%), compared with placebo (7.0%). Median frequencies for complex partial seizures and secondary generalized tonic-clonic seizures decreased with 200 mg per day of cenobamate (55.0% and 91.0%, respectively) and 400 mg per day of cenobamate (60.0% and 78.0%, respectively), compared with placebo (28.5% and 33.0%, respectively).

Compared with patients who received placebo, patients who received cenobamate were more likely to have greater than 50% reductions and 100% reductions in seizure frequency, Dr. Krauss said.

Investigators Adjusted Titration

The most common adverse events were somnolence, dizziness, headache, and balance disorder. The percentage of patients with common adverse events increased with dose, and slightly more patients who received 400 mg per day of cenobamate dropped out of the trial, compared with patients who received lower doses, Dr. Krauss said. Some patients with adverse events in the 400 mg group required modest dose reductions, and some adverse events were related to titration, he said.

Two allergic reactions occurred during initial rapid titration of the drug. After rapid dose titration for the first 10% of patients in the trial, doses for the remaining patients were titrated more slowly. One patient in the fast titration group developed drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Two patients in the trial had the common morbilliform rash without systemic signs—one during fast titration and one during slower titration.

Most adverse events were mild to moderate, and there were no deaths. In all, 37 adverse events occurred in 28 patients, and the number of adverse events was comparable between placebo and cenobamate, Dr. Krauss said. The most common serious adverse events were seizures in four patients, ataxias in two patients, dizziness in two patients, nystagmus in two patients, and suicidal ideation in two patients.

SK Life Science, based in Fair Lawn, New Jersey, is developing cenobamate.

—Jake Remaly

LOS ANGELES—Surgical intervention for epilepsy is often seen as a last resort, even among patients with drug-resistant focal epilepsies, said Gregory D. Cascino, MD, a neurologist at Mayo Clinic in Rochester, Minnesota. One reason for this phenomenon may be concern about potential adverse effects. Research indicates, however, that clinical and functional outcomes of surgery significantly surpass those of treatment with antiepileptic drugs (AEDs) in selected patients with drug-resistant focal epilepsy.

“The three important goals of epilepsy treatment are no seizures, no adverse effects, and no lifestyle limitations. This is what patients want when they seek neurologic care,” said Dr. Cascino at the 70th Annual Meeting of the American Academy of Neurology. “Seizure freedom is important because of its beneficial effects on quality of life, which include the ability to drive, pursue an education, have a career, and live independently with no need for a caregiver. We need to consider the risk of any intervention, whether it is medical or surgical, against the natural history of the disease.” All patients with epilepsy, not just those with drug-resistant focal epilepsy, are at significant risk of mortality due to seizure complications, progressive cognitive disorder, mood disorders, and even sudden unexpected death in epilepsy, he noted.

Identifying Surgical Candidates

“As soon as a patient is diagnosed with drug-resistant focal epilepsy, the neurologist probably should begin to triage for alternative forms of treatment,” Dr. Cascino said. “That doesn’t mean that patients need surgery on the first visit. But perhaps physicians should consider them for inpatient epilepsy monitoring and carefully review a high-resolution MRI head seizure protocol.”

Research suggests that patients who tend to have the best outcomes are those who have neuroimaging abnormalities resulting from substrate-directed pathology (eg, tumor, vascular anomaly, malformation of cortical development, or mesial temporal sclerosis) and undergo a complete resection of the epileptogenic lesion and the site of seizure onset. “These patients have the highest likelihood of being seizure-free after surgery, although some will have to continue taking AEDs to remain seizure-free,” Dr. Cascino said. Approximately 75% of patients with a surgically remediable epileptic syndrome who undergo epilepsy surgery become seizure-free.

Surgery Versus Medication

“When you compare best pharmaceutical treatment with best surgical practice, the numbers are strongly in favor of surgery, both in terms of efficacy and quality of life, for selected patients,” Dr. Cascino said. In one randomized controlled trial, 80 patients with temporal lobe epilepsy were randomly assigned 1:1 to surgery or optimal medical therapy with AEDs for one year. At one year, 58% of surgical patients were seizure-free versus 8% of the AED group. Quality of life was significantly higher among surgical patients. Four patients had adverse effects of surgery, and one patient in the AED group died.

Another randomized trial compared early referral to surgery of patients with drug-resistant mesial temporal lobe epilepsy with continued AED treatment for controlling seizures and improving quality of life. Although the study was halted prematurely due to slow accrual, none of the 23 patients in the AED group were seizure-free during year two of follow-up versus 11 of 15 surgery patients. Surgery had a significantly favorable treatment effect on quality of life. One person in the surgery group had a transient neurologic deficit attributed to postoperative stroke, and three participants in the medication group had status epilepticus.

Surgery in Patients With Normal MRI

One study followed 87 consecutive patients with normal MRI for one year after epilepsy surgery. “They all had temporal lobe epilepsy. Most of them had nonspecific gliosis, a few met the criteria for mesial temporal sclerosis, and none of them had tumors or lesions,” Dr. Cascino said. “About 55% were seizure-free, which compares quite favorably with neuromodulation and other treatments.” The best predictor of seizure freedom was unilateral interictal epileptiform discharge (IED) on scalp EEG and complete resection of brain regions generating IEDs on baseline intraoperative electrocorticography.

Another study demonstrated that the addition of PET to the diagnostic workup may improve outcomes. Among adults with PET-positive and MRI-negative temporal lobe epilepsy, three out of four were seizure-free postoperatively.

Trends in the Rate of Surgery

“Although there are high-quality clinical trials and major epilepsy surgical centers throughout the United States, the number of operative procedures for drug-resistant focal epilepsy has remained stable over the past 20 years,” Dr. Cascino said. “The patient population and surgical techniques have changed. The number of anterior temporal lobectomies may be decreasing, but more patients are being considered for surgery with MRI-negative extratemporal seizures or multifocal seizures.”

In one study, researchers examined epilepsy surgeries performed between 1991 and 2011 on 1,346 patients in nine major surgery centers in the US, Germany, and Australia. In eight centers, the highest number of surgeries for mesial temporal sclerosis occurred in 1991 or 2001, the researchers found. In 2011, the nine centers performed 48% fewer such surgeries, compared with 1991 or 2001, with a parallel increase in the performance of surgery for nonlesional epilepsy. In addition, the number of intracranial EEG implantations that did not lead to subsequent brain resections rose by 0.6% per year.

The study authors called for future research to improve the use of epilepsy surgery, to assess the effectiveness of various surgical procedures and presurgical evaluation tools, and to study extratemporal epilepsy, given its growing contribution to the surgical epilepsy burden.

—Adriene Marshall

Suggested Reading

Burkholder DB, Sulc V, Hoffman EM, et al. Interictal scalp electroencephalography and intraoperative electrocorticography in magnetic resonance imaging-negative temporal lobe epilepsy surgery. JAMA Neurol. 2014;71(6):702-709.

de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378(9800):1388-1395.

Engel J Jr, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012;307(9):922-930.

Jehi L, Friedman D, Carlson C, et al. The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia. Epilepsia. 2015;56(10):1526-1533.

Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA. 2015;313(3):285-293.

LoPinto-Khoury C, Sperling MR, Skidmore C, et al. Surgical outcome in PET-positive, MRI-negative patients with temporal lobe epilepsy. Epilepsia. 2012;53(2):342-348.

Mohammed HS, Kaufman CB, Limbrick DD, et al. Impact of epilepsy surgery on seizure control and quality of life: a 26-year follow-up study. Epilepsia. 2012;53(4):712-720.

Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311-318.

Zhang J, Liu W, Chen H, et al. Identification of common predictors of surgical outcomes for epilepsy surgery. Neuropsychiatr Dis Treat. 2013;9:1673-1682.

LOS ANGELES—Surgical intervention for epilepsy is often seen as a last resort, even among patients with drug-resistant focal epilepsies, said Gregory D. Cascino, MD, a neurologist at Mayo Clinic in Rochester, Minnesota. One reason for this phenomenon may be concern about potential adverse effects. Research indicates, however, that clinical and functional outcomes of surgery significantly surpass those of treatment with antiepileptic drugs (AEDs) in selected patients with drug-resistant focal epilepsy.

“The three important goals of epilepsy treatment are no seizures, no adverse effects, and no lifestyle limitations. This is what patients want when they seek neurologic care,” said Dr. Cascino at the 70th Annual Meeting of the American Academy of Neurology. “Seizure freedom is important because of its beneficial effects on quality of life, which include the ability to drive, pursue an education, have a career, and live independently with no need for a caregiver. We need to consider the risk of any intervention, whether it is medical or surgical, against the natural history of the disease.” All patients with epilepsy, not just those with drug-resistant focal epilepsy, are at significant risk of mortality due to seizure complications, progressive cognitive disorder, mood disorders, and even sudden unexpected death in epilepsy, he noted.

Identifying Surgical Candidates

“As soon as a patient is diagnosed with drug-resistant focal epilepsy, the neurologist probably should begin to triage for alternative forms of treatment,” Dr. Cascino said. “That doesn’t mean that patients need surgery on the first visit. But perhaps physicians should consider them for inpatient epilepsy monitoring and carefully review a high-resolution MRI head seizure protocol.”

Research suggests that patients who tend to have the best outcomes are those who have neuroimaging abnormalities resulting from substrate-directed pathology (eg, tumor, vascular anomaly, malformation of cortical development, or mesial temporal sclerosis) and undergo a complete resection of the epileptogenic lesion and the site of seizure onset. “These patients have the highest likelihood of being seizure-free after surgery, although some will have to continue taking AEDs to remain seizure-free,” Dr. Cascino said. Approximately 75% of patients with a surgically remediable epileptic syndrome who undergo epilepsy surgery become seizure-free.

Surgery Versus Medication

“When you compare best pharmaceutical treatment with best surgical practice, the numbers are strongly in favor of surgery, both in terms of efficacy and quality of life, for selected patients,” Dr. Cascino said. In one randomized controlled trial, 80 patients with temporal lobe epilepsy were randomly assigned 1:1 to surgery or optimal medical therapy with AEDs for one year. At one year, 58% of surgical patients were seizure-free versus 8% of the AED group. Quality of life was significantly higher among surgical patients. Four patients had adverse effects of surgery, and one patient in the AED group died.

Another randomized trial compared early referral to surgery of patients with drug-resistant mesial temporal lobe epilepsy with continued AED treatment for controlling seizures and improving quality of life. Although the study was halted prematurely due to slow accrual, none of the 23 patients in the AED group were seizure-free during year two of follow-up versus 11 of 15 surgery patients. Surgery had a significantly favorable treatment effect on quality of life. One person in the surgery group had a transient neurologic deficit attributed to postoperative stroke, and three participants in the medication group had status epilepticus.

Surgery in Patients With Normal MRI

One study followed 87 consecutive patients with normal MRI for one year after epilepsy surgery. “They all had temporal lobe epilepsy. Most of them had nonspecific gliosis, a few met the criteria for mesial temporal sclerosis, and none of them had tumors or lesions,” Dr. Cascino said. “About 55% were seizure-free, which compares quite favorably with neuromodulation and other treatments.” The best predictor of seizure freedom was unilateral interictal epileptiform discharge (IED) on scalp EEG and complete resection of brain regions generating IEDs on baseline intraoperative electrocorticography.

Another study demonstrated that the addition of PET to the diagnostic workup may improve outcomes. Among adults with PET-positive and MRI-negative temporal lobe epilepsy, three out of four were seizure-free postoperatively.

Trends in the Rate of Surgery

“Although there are high-quality clinical trials and major epilepsy surgical centers throughout the United States, the number of operative procedures for drug-resistant focal epilepsy has remained stable over the past 20 years,” Dr. Cascino said. “The patient population and surgical techniques have changed. The number of anterior temporal lobectomies may be decreasing, but more patients are being considered for surgery with MRI-negative extratemporal seizures or multifocal seizures.”

In one study, researchers examined epilepsy surgeries performed between 1991 and 2011 on 1,346 patients in nine major surgery centers in the US, Germany, and Australia. In eight centers, the highest number of surgeries for mesial temporal sclerosis occurred in 1991 or 2001, the researchers found. In 2011, the nine centers performed 48% fewer such surgeries, compared with 1991 or 2001, with a parallel increase in the performance of surgery for nonlesional epilepsy. In addition, the number of intracranial EEG implantations that did not lead to subsequent brain resections rose by 0.6% per year.

The study authors called for future research to improve the use of epilepsy surgery, to assess the effectiveness of various surgical procedures and presurgical evaluation tools, and to study extratemporal epilepsy, given its growing contribution to the surgical epilepsy burden.

—Adriene Marshall

Suggested Reading

Burkholder DB, Sulc V, Hoffman EM, et al. Interictal scalp electroencephalography and intraoperative electrocorticography in magnetic resonance imaging-negative temporal lobe epilepsy surgery. JAMA Neurol. 2014;71(6):702-709.

de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378(9800):1388-1395.

Engel J Jr, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012;307(9):922-930.

Jehi L, Friedman D, Carlson C, et al. The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia. Epilepsia. 2015;56(10):1526-1533.

Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA. 2015;313(3):285-293.

LoPinto-Khoury C, Sperling MR, Skidmore C, et al. Surgical outcome in PET-positive, MRI-negative patients with temporal lobe epilepsy. Epilepsia. 2012;53(2):342-348.

Mohammed HS, Kaufman CB, Limbrick DD, et al. Impact of epilepsy surgery on seizure control and quality of life: a 26-year follow-up study. Epilepsia. 2012;53(4):712-720.

Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311-318.

Zhang J, Liu W, Chen H, et al. Identification of common predictors of surgical outcomes for epilepsy surgery. Neuropsychiatr Dis Treat. 2013;9:1673-1682.

LOS ANGELES—Surgical intervention for epilepsy is often seen as a last resort, even among patients with drug-resistant focal epilepsies, said Gregory D. Cascino, MD, a neurologist at Mayo Clinic in Rochester, Minnesota. One reason for this phenomenon may be concern about potential adverse effects. Research indicates, however, that clinical and functional outcomes of surgery significantly surpass those of treatment with antiepileptic drugs (AEDs) in selected patients with drug-resistant focal epilepsy.

“The three important goals of epilepsy treatment are no seizures, no adverse effects, and no lifestyle limitations. This is what patients want when they seek neurologic care,” said Dr. Cascino at the 70th Annual Meeting of the American Academy of Neurology. “Seizure freedom is important because of its beneficial effects on quality of life, which include the ability to drive, pursue an education, have a career, and live independently with no need for a caregiver. We need to consider the risk of any intervention, whether it is medical or surgical, against the natural history of the disease.” All patients with epilepsy, not just those with drug-resistant focal epilepsy, are at significant risk of mortality due to seizure complications, progressive cognitive disorder, mood disorders, and even sudden unexpected death in epilepsy, he noted.

Identifying Surgical Candidates

“As soon as a patient is diagnosed with drug-resistant focal epilepsy, the neurologist probably should begin to triage for alternative forms of treatment,” Dr. Cascino said. “That doesn’t mean that patients need surgery on the first visit. But perhaps physicians should consider them for inpatient epilepsy monitoring and carefully review a high-resolution MRI head seizure protocol.”

Research suggests that patients who tend to have the best outcomes are those who have neuroimaging abnormalities resulting from substrate-directed pathology (eg, tumor, vascular anomaly, malformation of cortical development, or mesial temporal sclerosis) and undergo a complete resection of the epileptogenic lesion and the site of seizure onset. “These patients have the highest likelihood of being seizure-free after surgery, although some will have to continue taking AEDs to remain seizure-free,” Dr. Cascino said. Approximately 75% of patients with a surgically remediable epileptic syndrome who undergo epilepsy surgery become seizure-free.

Surgery Versus Medication

“When you compare best pharmaceutical treatment with best surgical practice, the numbers are strongly in favor of surgery, both in terms of efficacy and quality of life, for selected patients,” Dr. Cascino said. In one randomized controlled trial, 80 patients with temporal lobe epilepsy were randomly assigned 1:1 to surgery or optimal medical therapy with AEDs for one year. At one year, 58% of surgical patients were seizure-free versus 8% of the AED group. Quality of life was significantly higher among surgical patients. Four patients had adverse effects of surgery, and one patient in the AED group died.

Another randomized trial compared early referral to surgery of patients with drug-resistant mesial temporal lobe epilepsy with continued AED treatment for controlling seizures and improving quality of life. Although the study was halted prematurely due to slow accrual, none of the 23 patients in the AED group were seizure-free during year two of follow-up versus 11 of 15 surgery patients. Surgery had a significantly favorable treatment effect on quality of life. One person in the surgery group had a transient neurologic deficit attributed to postoperative stroke, and three participants in the medication group had status epilepticus.

Surgery in Patients With Normal MRI

One study followed 87 consecutive patients with normal MRI for one year after epilepsy surgery. “They all had temporal lobe epilepsy. Most of them had nonspecific gliosis, a few met the criteria for mesial temporal sclerosis, and none of them had tumors or lesions,” Dr. Cascino said. “About 55% were seizure-free, which compares quite favorably with neuromodulation and other treatments.” The best predictor of seizure freedom was unilateral interictal epileptiform discharge (IED) on scalp EEG and complete resection of brain regions generating IEDs on baseline intraoperative electrocorticography.

Another study demonstrated that the addition of PET to the diagnostic workup may improve outcomes. Among adults with PET-positive and MRI-negative temporal lobe epilepsy, three out of four were seizure-free postoperatively.

Trends in the Rate of Surgery

“Although there are high-quality clinical trials and major epilepsy surgical centers throughout the United States, the number of operative procedures for drug-resistant focal epilepsy has remained stable over the past 20 years,” Dr. Cascino said. “The patient population and surgical techniques have changed. The number of anterior temporal lobectomies may be decreasing, but more patients are being considered for surgery with MRI-negative extratemporal seizures or multifocal seizures.”

In one study, researchers examined epilepsy surgeries performed between 1991 and 2011 on 1,346 patients in nine major surgery centers in the US, Germany, and Australia. In eight centers, the highest number of surgeries for mesial temporal sclerosis occurred in 1991 or 2001, the researchers found. In 2011, the nine centers performed 48% fewer such surgeries, compared with 1991 or 2001, with a parallel increase in the performance of surgery for nonlesional epilepsy. In addition, the number of intracranial EEG implantations that did not lead to subsequent brain resections rose by 0.6% per year.

The study authors called for future research to improve the use of epilepsy surgery, to assess the effectiveness of various surgical procedures and presurgical evaluation tools, and to study extratemporal epilepsy, given its growing contribution to the surgical epilepsy burden.

—Adriene Marshall

Suggested Reading

Burkholder DB, Sulc V, Hoffman EM, et al. Interictal scalp electroencephalography and intraoperative electrocorticography in magnetic resonance imaging-negative temporal lobe epilepsy surgery. JAMA Neurol. 2014;71(6):702-709.

de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378(9800):1388-1395.

Engel J Jr, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012;307(9):922-930.

Jehi L, Friedman D, Carlson C, et al. The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia. Epilepsia. 2015;56(10):1526-1533.

Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA. 2015;313(3):285-293.

LoPinto-Khoury C, Sperling MR, Skidmore C, et al. Surgical outcome in PET-positive, MRI-negative patients with temporal lobe epilepsy. Epilepsia. 2012;53(2):342-348.

Mohammed HS, Kaufman CB, Limbrick DD, et al. Impact of epilepsy surgery on seizure control and quality of life: a 26-year follow-up study. Epilepsia. 2012;53(4):712-720.

Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311-318.

Zhang J, Liu W, Chen H, et al. Identification of common predictors of surgical outcomes for epilepsy surgery. Neuropsychiatr Dis Treat. 2013;9:1673-1682.

The FDA has approved Epidiolex (cannabidiol [CBD]) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a derivative of marijuana. It also is the first drug approved by the FDA for the treatment of Dravet syndrome.

The approval was based on three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Epidiolex taken with other epilepsy medications reduced the frequency of seizures, compared with placebo. The most common side effects included lethargy, elevated liver enzymes, decreased appetite, diarrhea, rash, weakness, sleep disorder, and infection.

“Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to support rigorous scientific research on the potential medical uses of marijuana-derived products…. But at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims.”

The FDA has approved Epidiolex (cannabidiol [CBD]) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a derivative of marijuana. It also is the first drug approved by the FDA for the treatment of Dravet syndrome.

The approval was based on three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Epidiolex taken with other epilepsy medications reduced the frequency of seizures, compared with placebo. The most common side effects included lethargy, elevated liver enzymes, decreased appetite, diarrhea, rash, weakness, sleep disorder, and infection.

“Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to support rigorous scientific research on the potential medical uses of marijuana-derived products…. But at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims.”

The FDA has approved Epidiolex (cannabidiol [CBD]) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a derivative of marijuana. It also is the first drug approved by the FDA for the treatment of Dravet syndrome.

The approval was based on three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Epidiolex taken with other epilepsy medications reduced the frequency of seizures, compared with placebo. The most common side effects included lethargy, elevated liver enzymes, decreased appetite, diarrhea, rash, weakness, sleep disorder, and infection.

“Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to support rigorous scientific research on the potential medical uses of marijuana-derived products…. But at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims.”

A ketogenic diet appears to be effective for children with refractory status epilepticus (RSE) suggests a small trial that included 14 patients.

• A study conducted by the Status Epilepticus Research Group from January 2011 to December 2016 found that 71% of patients with refractory status epilepticus who received a ketogenic diet experienced seizure resolution, verified by EEG findings, within 7 days of starting the regimen.
• 79% of the children with RSE were weaned off enteral infusions of the diet within 14 days.
• Possible adverse effects from the ketogenic diet occurred in 3 of 14 patients, including gastrointestinal paresis and elevated triglyceride levels.
• The regimen produced ketosis within a median of 2 days after it was initiated.
• By 3 months, 4 patients were still seizure free and 3 had fewer seizures.

pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018;144:1-6.

A ketogenic diet appears to be effective for children with refractory status epilepticus (RSE) suggests a small trial that included 14 patients.

• A study conducted by the Status Epilepticus Research Group from January 2011 to December 2016 found that 71% of patients with refractory status epilepticus who received a ketogenic diet experienced seizure resolution, verified by EEG findings, within 7 days of starting the regimen.
• 79% of the children with RSE were weaned off enteral infusions of the diet within 14 days.
• Possible adverse effects from the ketogenic diet occurred in 3 of 14 patients, including gastrointestinal paresis and elevated triglyceride levels.
• The regimen produced ketosis within a median of 2 days after it was initiated.
• By 3 months, 4 patients were still seizure free and 3 had fewer seizures.

pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018;144:1-6.

A ketogenic diet appears to be effective for children with refractory status epilepticus (RSE) suggests a small trial that included 14 patients.

• A study conducted by the Status Epilepticus Research Group from January 2011 to December 2016 found that 71% of patients with refractory status epilepticus who received a ketogenic diet experienced seizure resolution, verified by EEG findings, within 7 days of starting the regimen.
• 79% of the children with RSE were weaned off enteral infusions of the diet within 14 days.
• Possible adverse effects from the ketogenic diet occurred in 3 of 14 patients, including gastrointestinal paresis and elevated triglyceride levels.
• The regimen produced ketosis within a median of 2 days after it was initiated.
• By 3 months, 4 patients were still seizure free and 3 had fewer seizures.

pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018;144:1-6.

The epilepsy associated with focal cortical dysplasia remains a major challenge, but early recognition of the disorder will allow clinicians to consider the possibility of resective surgery, which has been shown to eliminate seizures in some patients.

• A recent review of the medical literature found that most children with focal cortical dysplasia have intractable focal epilepsy.
• The epilepsy observed in patients with focal cortical dysplasia is related to activation of the mTOR pathway and altered receptor neurotransmission.
• The literature review discusses the epidemiology, natural history, and mechanisms that precipitate seizures in children with focal cortical dysplasia.
• Between 25% and 29% of children in a surgical series had focal cortical dysplasia.

Challenges in managing epilepsy associated with focal cortical dysplasia in children. Epilepsy Res. 2018;145:1-17.

The epilepsy associated with focal cortical dysplasia remains a major challenge, but early recognition of the disorder will allow clinicians to consider the possibility of resective surgery, which has been shown to eliminate seizures in some patients.

• A recent review of the medical literature found that most children with focal cortical dysplasia have intractable focal epilepsy.
• The epilepsy observed in patients with focal cortical dysplasia is related to activation of the mTOR pathway and altered receptor neurotransmission.
• The literature review discusses the epidemiology, natural history, and mechanisms that precipitate seizures in children with focal cortical dysplasia.
• Between 25% and 29% of children in a surgical series had focal cortical dysplasia.

Challenges in managing epilepsy associated with focal cortical dysplasia in children. Epilepsy Res. 2018;145:1-17.

The epilepsy associated with focal cortical dysplasia remains a major challenge, but early recognition of the disorder will allow clinicians to consider the possibility of resective surgery, which has been shown to eliminate seizures in some patients.

• A recent review of the medical literature found that most children with focal cortical dysplasia have intractable focal epilepsy.
• The epilepsy observed in patients with focal cortical dysplasia is related to activation of the mTOR pathway and altered receptor neurotransmission.
• The literature review discusses the epidemiology, natural history, and mechanisms that precipitate seizures in children with focal cortical dysplasia.
• Between 25% and 29% of children in a surgical series had focal cortical dysplasia.

Challenges in managing epilepsy associated with focal cortical dysplasia in children. Epilepsy Res. 2018;145:1-17.

Drug therapy for pregnant women with epilepsy has changed markedly in recent years according to analysis of data from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.

• MONEAD, an NIH-funded, observational, multicenter study that looked at pregnancy outcomes in mothers and their children, included women ages 14-45 years and up to 20 weeks pregnant.
• Among 351 pregnant women with epilepsy enrolled in the study, 73.8% (259) were on monotherapy and 21.9% (77) on polytherapy; 4% were not taking an antiepileptic drug.
• Lamotrigine was the most popular drug in women on monotherapy, followed by levetiracetam, carbamazepine, zonisamide, oxcarbazepine, and topiramate.
• The most common polypharmacy regimen included  lamotrigine and levetiracetam.

The researchers point out that these percentages only reflect drug usage in US tertiary epilepsy centers and may not indicate usage in community practice.

MONEAD Investigator Group. Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy. Epilepsy Behav. 2018;84:10-14.

Drug therapy for pregnant women with epilepsy has changed markedly in recent years according to analysis of data from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.

• MONEAD, an NIH-funded, observational, multicenter study that looked at pregnancy outcomes in mothers and their children, included women ages 14-45 years and up to 20 weeks pregnant.
• Among 351 pregnant women with epilepsy enrolled in the study, 73.8% (259) were on monotherapy and 21.9% (77) on polytherapy; 4% were not taking an antiepileptic drug.
• Lamotrigine was the most popular drug in women on monotherapy, followed by levetiracetam, carbamazepine, zonisamide, oxcarbazepine, and topiramate.
• The most common polypharmacy regimen included  lamotrigine and levetiracetam.

The researchers point out that these percentages only reflect drug usage in US tertiary epilepsy centers and may not indicate usage in community practice.

MONEAD Investigator Group. Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy. Epilepsy Behav. 2018;84:10-14.

Drug therapy for pregnant women with epilepsy has changed markedly in recent years according to analysis of data from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study.

• MONEAD, an NIH-funded, observational, multicenter study that looked at pregnancy outcomes in mothers and their children, included women ages 14-45 years and up to 20 weeks pregnant.
• Among 351 pregnant women with epilepsy enrolled in the study, 73.8% (259) were on monotherapy and 21.9% (77) on polytherapy; 4% were not taking an antiepileptic drug.
• Lamotrigine was the most popular drug in women on monotherapy, followed by levetiracetam, carbamazepine, zonisamide, oxcarbazepine, and topiramate.
• The most common polypharmacy regimen included  lamotrigine and levetiracetam.

The researchers point out that these percentages only reflect drug usage in US tertiary epilepsy centers and may not indicate usage in community practice.

MONEAD Investigator Group. Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy. Epilepsy Behav. 2018;84:10-14.

Pediatric refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) remain life-threatening disorders whose etiology and effective management are elusive according to a review in Seizure.

• RSE is defined as a disorder that doesn’t respond to first and second line antiepileptic agents.
• SRSE refers to status epilepticus that continues for at least 24 hours after anesthetic agents have been given or which recurs once the drugs are stopped.
• The evidence to support current treatment options is not based on randomized clinical trials but instead relies on case series and expert opinions.
• The most common treatment for both disorders is continuous IV infusion of anesthetic drugs but the best dosing and the optimal administration rate remain controversial.
• Some clinicians have used non-drug approaches to RSE and SRSE but the evidence supporting these options is limited.

Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super refractory status epilepticus [Published online ahead of print May 19, 2018]. Seizure. DOI: https://doi.org/10.1016/j.seizure.2018.05.012.

Pediatric refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) remain life-threatening disorders whose etiology and effective management are elusive according to a review in Seizure.

• RSE is defined as a disorder that doesn’t respond to first and second line antiepileptic agents.
• SRSE refers to status epilepticus that continues for at least 24 hours after anesthetic agents have been given or which recurs once the drugs are stopped.
• The evidence to support current treatment options is not based on randomized clinical trials but instead relies on case series and expert opinions.
• The most common treatment for both disorders is continuous IV infusion of anesthetic drugs but the best dosing and the optimal administration rate remain controversial.
• Some clinicians have used non-drug approaches to RSE and SRSE but the evidence supporting these options is limited.

Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super refractory status epilepticus [Published online ahead of print May 19, 2018]. Seizure. DOI: https://doi.org/10.1016/j.seizure.2018.05.012.

Pediatric refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) remain life-threatening disorders whose etiology and effective management are elusive according to a review in Seizure.

• RSE is defined as a disorder that doesn’t respond to first and second line antiepileptic agents.
• SRSE refers to status epilepticus that continues for at least 24 hours after anesthetic agents have been given or which recurs once the drugs are stopped.
• The evidence to support current treatment options is not based on randomized clinical trials but instead relies on case series and expert opinions.
• The most common treatment for both disorders is continuous IV infusion of anesthetic drugs but the best dosing and the optimal administration rate remain controversial.
• Some clinicians have used non-drug approaches to RSE and SRSE but the evidence supporting these options is limited.

Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super refractory status epilepticus [Published online ahead of print May 19, 2018]. Seizure. DOI: https://doi.org/10.1016/j.seizure.2018.05.012.