Epilepsy & Seizures

Hypertension, diabetes, and smoking in midlife are potentially modifiable risk factors for late-onset epilepsy, according to a study that also found an increased risk with the apolipoprotein E4 (APOE4) genotype and in black individuals.

ricky_68fr/fotolia

Emily L. Johnson, MD, of Johns Hopkins University, Baltimore, and her coauthors analyzed data from 10,420 participants in the Atherosclerosis Risk in Communities prospective cohort study and found 596 who developed late-onset epilepsy (LOE), defined as recurrent unprovoked seizures starting at 60 years or older.

The study, published online July 23 in JAMA Neurology, showed that individuals with hypertension at baseline had a 30% higher risk of LOE, those who smoked had a 9% higher risk, and those with diabetes had a 45% higher risk. However, the increased risk associated with smoking was evident only in women, who had a 27% higher risk.

Participants with incident stroke had a 3.38-fold higher risk of LOE, and those with dementia had a 2.56-fold higher risk, Dr. Johnson and her colleagues reported.

“The association of LOE with vascular and lifestyle risk factors persisted after participants with diagnosis of clinical stroke or dementia were included or censored, suggesting that these risk factors may contribute to LOE even in the absence of dementia or clinical stroke,” the investigators wrote.

However, higher levels of physical activity decreased the risk by 10%, and moderate alcohol consumption – defined as 1-7 standard drinks per week – was associated with a 28% reduction.

Race and geographic location both influenced the risk of LOE; black participants showed a 66% higher risk, compared with whites, and black participants in Mississippi and North Carolina had a higher risk than did North Carolina white participants. The highest risk of LOE was seen in black participants with diabetes.

“The reasons for the different incidences of LOE by race/ethnicity may be owing to differing effects of comorbidities, such as diabetes, for which we found a significantly higher effect in black individuals than in white individuals,” the authors wrote.

Individuals who had one APOE4 allele showed a 46% higher risk, and those with two alleles showed a 2.57-fold higher risk.

“The APOE4 genotype is the major genetic risk factor for Alzheimer’s disease, which is associated with epilepsy; however, no prior association between APOE4 and LOE has previously been shown,” the authors reported.

The researchers noted that their findings suggested that lifestyle modifications earlier in life could mitigate some of the risk factors associated with LOE, and could also help identify patients at higher risk for the disease.

No funding was declared. One author declared consultancy and investigator positions with private industry.

SOURCE: Johnson E et al. JAMA Neurol, 2018 July 23. doi: 10.1001/jamaneurol.2018.1935.
 

Hypertension, diabetes, and smoking in midlife are potentially modifiable risk factors for late-onset epilepsy, according to a study that also found an increased risk with the apolipoprotein E4 (APOE4) genotype and in black individuals.

ricky_68fr/fotolia

Emily L. Johnson, MD, of Johns Hopkins University, Baltimore, and her coauthors analyzed data from 10,420 participants in the Atherosclerosis Risk in Communities prospective cohort study and found 596 who developed late-onset epilepsy (LOE), defined as recurrent unprovoked seizures starting at 60 years or older.

The study, published online July 23 in JAMA Neurology, showed that individuals with hypertension at baseline had a 30% higher risk of LOE, those who smoked had a 9% higher risk, and those with diabetes had a 45% higher risk. However, the increased risk associated with smoking was evident only in women, who had a 27% higher risk.

Participants with incident stroke had a 3.38-fold higher risk of LOE, and those with dementia had a 2.56-fold higher risk, Dr. Johnson and her colleagues reported.

“The association of LOE with vascular and lifestyle risk factors persisted after participants with diagnosis of clinical stroke or dementia were included or censored, suggesting that these risk factors may contribute to LOE even in the absence of dementia or clinical stroke,” the investigators wrote.

However, higher levels of physical activity decreased the risk by 10%, and moderate alcohol consumption – defined as 1-7 standard drinks per week – was associated with a 28% reduction.

Race and geographic location both influenced the risk of LOE; black participants showed a 66% higher risk, compared with whites, and black participants in Mississippi and North Carolina had a higher risk than did North Carolina white participants. The highest risk of LOE was seen in black participants with diabetes.

“The reasons for the different incidences of LOE by race/ethnicity may be owing to differing effects of comorbidities, such as diabetes, for which we found a significantly higher effect in black individuals than in white individuals,” the authors wrote.

Individuals who had one APOE4 allele showed a 46% higher risk, and those with two alleles showed a 2.57-fold higher risk.

“The APOE4 genotype is the major genetic risk factor for Alzheimer’s disease, which is associated with epilepsy; however, no prior association between APOE4 and LOE has previously been shown,” the authors reported.

The researchers noted that their findings suggested that lifestyle modifications earlier in life could mitigate some of the risk factors associated with LOE, and could also help identify patients at higher risk for the disease.

No funding was declared. One author declared consultancy and investigator positions with private industry.

SOURCE: Johnson E et al. JAMA Neurol, 2018 July 23. doi: 10.1001/jamaneurol.2018.1935.
 

Hypertension, diabetes, and smoking in midlife are potentially modifiable risk factors for late-onset epilepsy, according to a study that also found an increased risk with the apolipoprotein E4 (APOE4) genotype and in black individuals.

ricky_68fr/fotolia

Emily L. Johnson, MD, of Johns Hopkins University, Baltimore, and her coauthors analyzed data from 10,420 participants in the Atherosclerosis Risk in Communities prospective cohort study and found 596 who developed late-onset epilepsy (LOE), defined as recurrent unprovoked seizures starting at 60 years or older.

The study, published online July 23 in JAMA Neurology, showed that individuals with hypertension at baseline had a 30% higher risk of LOE, those who smoked had a 9% higher risk, and those with diabetes had a 45% higher risk. However, the increased risk associated with smoking was evident only in women, who had a 27% higher risk.

Participants with incident stroke had a 3.38-fold higher risk of LOE, and those with dementia had a 2.56-fold higher risk, Dr. Johnson and her colleagues reported.

“The association of LOE with vascular and lifestyle risk factors persisted after participants with diagnosis of clinical stroke or dementia were included or censored, suggesting that these risk factors may contribute to LOE even in the absence of dementia or clinical stroke,” the investigators wrote.

However, higher levels of physical activity decreased the risk by 10%, and moderate alcohol consumption – defined as 1-7 standard drinks per week – was associated with a 28% reduction.

Race and geographic location both influenced the risk of LOE; black participants showed a 66% higher risk, compared with whites, and black participants in Mississippi and North Carolina had a higher risk than did North Carolina white participants. The highest risk of LOE was seen in black participants with diabetes.

“The reasons for the different incidences of LOE by race/ethnicity may be owing to differing effects of comorbidities, such as diabetes, for which we found a significantly higher effect in black individuals than in white individuals,” the authors wrote.

Individuals who had one APOE4 allele showed a 46% higher risk, and those with two alleles showed a 2.57-fold higher risk.

“The APOE4 genotype is the major genetic risk factor for Alzheimer’s disease, which is associated with epilepsy; however, no prior association between APOE4 and LOE has previously been shown,” the authors reported.

The researchers noted that their findings suggested that lifestyle modifications earlier in life could mitigate some of the risk factors associated with LOE, and could also help identify patients at higher risk for the disease.

No funding was declared. One author declared consultancy and investigator positions with private industry.

SOURCE: Johnson E et al. JAMA Neurol, 2018 July 23. doi: 10.1001/jamaneurol.2018.1935.
 

Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests.

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“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”

As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”

The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.

“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”

For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)

The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.

Of the total nonindex seizures, 46% of those resulted in neuroimaging.

“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.

False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.

“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”

At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.

A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.

As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”

The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.

No study funding was reported, and the authors reported no relevant disclosures.

SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518

Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests.

Spotmatik/Thinkstock

“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”

As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”

The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.

“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”

For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)

The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.

Of the total nonindex seizures, 46% of those resulted in neuroimaging.

“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.

False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.

“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”

At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.

A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.

As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”

The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.

No study funding was reported, and the authors reported no relevant disclosures.

SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518

Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests.

Spotmatik/Thinkstock

“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”

As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”

The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.

“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”

For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)

The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.

Of the total nonindex seizures, 46% of those resulted in neuroimaging.

“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.

False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.

“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”

At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.

A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.

As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”

The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.

No study funding was reported, and the authors reported no relevant disclosures.

SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518

TORONTO – Researchers at UCSF Benioff Children’s Hospital in San Francisco implemented a novel intervention that leveraged existing in-room technology to expedite antiepileptic drug administration to inpatients having a seizure.

With the quality initiative, they were able to decrease median time from seizure onset to benzodiazepine (BZD) administration from 7 minutes (preintervention) to 2 minutes (post intervention) and reduce the median time from order to administration of second-phase non-BZDs from 28 minutes to 11 minutes.

©drpnncpp/thinkstockphotos.com

“Leveraging existing patient room technology to mobilize pharmacy to the bedside expedited non-BZD administration by 60%,” reported principal investigator Arpi Bekmezian, MD, a pediatric hospitalist and medical director of quality and safety at Benioff Children’s Hospital. She presented the findings at the Pediatric Academic Societies annual meeting.

“Furthermore, the rapid-response seizure rescue process may have created an increased sense of urgency helping to expedite initial BZD administration by 70%. ... This may have prevented the need for second-phase therapy and progression to status epilepticus, potentially minimizing the risk of neuronal injury, and all without the additional resources of a Code team.”

Early and rapid escalation of treatment is critical to prevent neuronal injury in patients with status epilepticus. Guidelines recommend initial antiepileptic therapy at 5 minutes, with rapid escalation to second-phase therapy if the seizure persists.

Preintervention baseline data from UCSF Benioff Children’s indicated a 7-minute lag time from seizure onset to BZD therapy and a 28-minute lag from order to administration of non-BZDs (phenobarbital, phenytoin, levetiracetam, valproic acid). Other studies have shown significantly greater delays to antiepileptic treatment.

“That was just too long, and it matched our clinical experience of being at the bedside of a seizing patient and wondering why the medication was taking so long to arrive from the pharmacy.”

The researchers set out to reduce time to BZD administration from 7 minutes to 5 minutes or less and to reduce time to second-phase non-BZD administration to less than 10 minutes. To accomplish this, a multidisciplinary team that included leadership from physicians, pharmacy, and nursing defined primary and secondary drivers of efficiency, with interventions targeting both team communication and medication delivery.

The intervention period lasted 16 months, during which time there were 61 seizure events requiring urgent antiepileptic treatment. Complete data were available for 57 seizures.

Among the interventions they implemented was to stock all medication-dispensing stations with intranasal/buccal BZD available on “nursing override” for easy access and administration.

Because non-BZDs require pharmacy compounding, and the main pharmacy receives many STAT orders with competing priorities, they developed a hospitalwide “seizure rescue” (SR) process by using patient-room staff terminals to activate a dedicated individual from the pharmacy, who would then report to the bedside with a backpack stocked with non-BZDs ready to compound. Nurses were trained to press the SR button for any seizure that may require urgent therapy.

“We didn’t want nurses to waste time on the phone [calling pharmacy], and we considered calling a Code, but we couldn’t really justify the resource utilization as most of these patients didn’t have respiratory compromise, and they didn’t need the whole Code team,” said Dr. Bekmezian. She noted that her hospital strongly discourages bedside compounding by nursing staff.

Instead, they realized they could easily reprogram the patient-room electronic staff terminals to have a dedicated SR button that would directly alert a dedicated pharmacist carrying the SR phone. The pharmacist could then swipe and confirm that they received the alert and let the nurse know they were on the way, “and this would free up the nurse to go ahead and obtain the benzodiazepines and administer them as pharmacy made their way to the room.”

“To our knowledge, this is the first study to report expediting antiepileptic drug delivery to patients in the hospital,” said Dr. Bekmezian. She noted that less than 50% of cases actually required pharmacist response, “but the pharmacy staff chose to be activated earlier in the management algorithm to avoid delays in treatment.”

UCSF Children’s Hospital San Francisco campus is a 183-bed, tertiary care, teaching children’s hospital that has pediatric, neonatal, and cardiac intensive care units and set-down units. They provide liver, bone marrow, kidney, and cardiac transplantation and have more than 10,000 annual admissions.

The investigators reported no conflicts of interest.

SOURCE: Bekmezian A et al. PAS 2018. Abstract 3545.3.

TORONTO – Researchers at UCSF Benioff Children’s Hospital in San Francisco implemented a novel intervention that leveraged existing in-room technology to expedite antiepileptic drug administration to inpatients having a seizure.

With the quality initiative, they were able to decrease median time from seizure onset to benzodiazepine (BZD) administration from 7 minutes (preintervention) to 2 minutes (post intervention) and reduce the median time from order to administration of second-phase non-BZDs from 28 minutes to 11 minutes.

©drpnncpp/thinkstockphotos.com

“Leveraging existing patient room technology to mobilize pharmacy to the bedside expedited non-BZD administration by 60%,” reported principal investigator Arpi Bekmezian, MD, a pediatric hospitalist and medical director of quality and safety at Benioff Children’s Hospital. She presented the findings at the Pediatric Academic Societies annual meeting.

“Furthermore, the rapid-response seizure rescue process may have created an increased sense of urgency helping to expedite initial BZD administration by 70%. ... This may have prevented the need for second-phase therapy and progression to status epilepticus, potentially minimizing the risk of neuronal injury, and all without the additional resources of a Code team.”

Early and rapid escalation of treatment is critical to prevent neuronal injury in patients with status epilepticus. Guidelines recommend initial antiepileptic therapy at 5 minutes, with rapid escalation to second-phase therapy if the seizure persists.

Preintervention baseline data from UCSF Benioff Children’s indicated a 7-minute lag time from seizure onset to BZD therapy and a 28-minute lag from order to administration of non-BZDs (phenobarbital, phenytoin, levetiracetam, valproic acid). Other studies have shown significantly greater delays to antiepileptic treatment.

“That was just too long, and it matched our clinical experience of being at the bedside of a seizing patient and wondering why the medication was taking so long to arrive from the pharmacy.”

The researchers set out to reduce time to BZD administration from 7 minutes to 5 minutes or less and to reduce time to second-phase non-BZD administration to less than 10 minutes. To accomplish this, a multidisciplinary team that included leadership from physicians, pharmacy, and nursing defined primary and secondary drivers of efficiency, with interventions targeting both team communication and medication delivery.

The intervention period lasted 16 months, during which time there were 61 seizure events requiring urgent antiepileptic treatment. Complete data were available for 57 seizures.

Among the interventions they implemented was to stock all medication-dispensing stations with intranasal/buccal BZD available on “nursing override” for easy access and administration.

Because non-BZDs require pharmacy compounding, and the main pharmacy receives many STAT orders with competing priorities, they developed a hospitalwide “seizure rescue” (SR) process by using patient-room staff terminals to activate a dedicated individual from the pharmacy, who would then report to the bedside with a backpack stocked with non-BZDs ready to compound. Nurses were trained to press the SR button for any seizure that may require urgent therapy.

“We didn’t want nurses to waste time on the phone [calling pharmacy], and we considered calling a Code, but we couldn’t really justify the resource utilization as most of these patients didn’t have respiratory compromise, and they didn’t need the whole Code team,” said Dr. Bekmezian. She noted that her hospital strongly discourages bedside compounding by nursing staff.

Instead, they realized they could easily reprogram the patient-room electronic staff terminals to have a dedicated SR button that would directly alert a dedicated pharmacist carrying the SR phone. The pharmacist could then swipe and confirm that they received the alert and let the nurse know they were on the way, “and this would free up the nurse to go ahead and obtain the benzodiazepines and administer them as pharmacy made their way to the room.”

“To our knowledge, this is the first study to report expediting antiepileptic drug delivery to patients in the hospital,” said Dr. Bekmezian. She noted that less than 50% of cases actually required pharmacist response, “but the pharmacy staff chose to be activated earlier in the management algorithm to avoid delays in treatment.”

UCSF Children’s Hospital San Francisco campus is a 183-bed, tertiary care, teaching children’s hospital that has pediatric, neonatal, and cardiac intensive care units and set-down units. They provide liver, bone marrow, kidney, and cardiac transplantation and have more than 10,000 annual admissions.

The investigators reported no conflicts of interest.

SOURCE: Bekmezian A et al. PAS 2018. Abstract 3545.3.

TORONTO – Researchers at UCSF Benioff Children’s Hospital in San Francisco implemented a novel intervention that leveraged existing in-room technology to expedite antiepileptic drug administration to inpatients having a seizure.

With the quality initiative, they were able to decrease median time from seizure onset to benzodiazepine (BZD) administration from 7 minutes (preintervention) to 2 minutes (post intervention) and reduce the median time from order to administration of second-phase non-BZDs from 28 minutes to 11 minutes.

©drpnncpp/thinkstockphotos.com

“Leveraging existing patient room technology to mobilize pharmacy to the bedside expedited non-BZD administration by 60%,” reported principal investigator Arpi Bekmezian, MD, a pediatric hospitalist and medical director of quality and safety at Benioff Children’s Hospital. She presented the findings at the Pediatric Academic Societies annual meeting.

“Furthermore, the rapid-response seizure rescue process may have created an increased sense of urgency helping to expedite initial BZD administration by 70%. ... This may have prevented the need for second-phase therapy and progression to status epilepticus, potentially minimizing the risk of neuronal injury, and all without the additional resources of a Code team.”

Early and rapid escalation of treatment is critical to prevent neuronal injury in patients with status epilepticus. Guidelines recommend initial antiepileptic therapy at 5 minutes, with rapid escalation to second-phase therapy if the seizure persists.

Preintervention baseline data from UCSF Benioff Children’s indicated a 7-minute lag time from seizure onset to BZD therapy and a 28-minute lag from order to administration of non-BZDs (phenobarbital, phenytoin, levetiracetam, valproic acid). Other studies have shown significantly greater delays to antiepileptic treatment.

“That was just too long, and it matched our clinical experience of being at the bedside of a seizing patient and wondering why the medication was taking so long to arrive from the pharmacy.”

The researchers set out to reduce time to BZD administration from 7 minutes to 5 minutes or less and to reduce time to second-phase non-BZD administration to less than 10 minutes. To accomplish this, a multidisciplinary team that included leadership from physicians, pharmacy, and nursing defined primary and secondary drivers of efficiency, with interventions targeting both team communication and medication delivery.

The intervention period lasted 16 months, during which time there were 61 seizure events requiring urgent antiepileptic treatment. Complete data were available for 57 seizures.

Among the interventions they implemented was to stock all medication-dispensing stations with intranasal/buccal BZD available on “nursing override” for easy access and administration.

Because non-BZDs require pharmacy compounding, and the main pharmacy receives many STAT orders with competing priorities, they developed a hospitalwide “seizure rescue” (SR) process by using patient-room staff terminals to activate a dedicated individual from the pharmacy, who would then report to the bedside with a backpack stocked with non-BZDs ready to compound. Nurses were trained to press the SR button for any seizure that may require urgent therapy.

“We didn’t want nurses to waste time on the phone [calling pharmacy], and we considered calling a Code, but we couldn’t really justify the resource utilization as most of these patients didn’t have respiratory compromise, and they didn’t need the whole Code team,” said Dr. Bekmezian. She noted that her hospital strongly discourages bedside compounding by nursing staff.

Instead, they realized they could easily reprogram the patient-room electronic staff terminals to have a dedicated SR button that would directly alert a dedicated pharmacist carrying the SR phone. The pharmacist could then swipe and confirm that they received the alert and let the nurse know they were on the way, “and this would free up the nurse to go ahead and obtain the benzodiazepines and administer them as pharmacy made their way to the room.”

“To our knowledge, this is the first study to report expediting antiepileptic drug delivery to patients in the hospital,” said Dr. Bekmezian. She noted that less than 50% of cases actually required pharmacist response, “but the pharmacy staff chose to be activated earlier in the management algorithm to avoid delays in treatment.”

UCSF Children’s Hospital San Francisco campus is a 183-bed, tertiary care, teaching children’s hospital that has pediatric, neonatal, and cardiac intensive care units and set-down units. They provide liver, bone marrow, kidney, and cardiac transplantation and have more than 10,000 annual admissions.

The investigators reported no conflicts of interest.

SOURCE: Bekmezian A et al. PAS 2018. Abstract 3545.3.

Family caregivers of patients with intractable epilepsy are subject to significant stigma because of societal views about the disorder, according to cross-sectional analysis recently published in Epilepsy and Behavior.

• Self-administered surveys were taken by caregivers of adults and children with a confirmed diagnosis of intractable epilepsy.
• Affiliate stigma was defined as perceiving and internalizing negative societal views of the disorder and having a psychological response to those views.
• Caregivers’ psychological burdens were measured using the 30-item Carer’s Assessment of Difficulties Index and the stigma was evaluated with a separate 6-item scale that measured their perceptions of stigma.
• The 136 respondents were mostly white, female, and married.
• Investigators found the link between the stigma of epilepsy and the burden caregivers experienced was stronger among family members caring for adult patients.

Hansena B, Szaflarski M, Bebin EB, Szaflarski JP. Affiliate stigma and caregiver burden in intractable epilepsy. Epilepsy Behav. 2018;85:1-6.

Family caregivers of patients with intractable epilepsy are subject to significant stigma because of societal views about the disorder, according to cross-sectional analysis recently published in Epilepsy and Behavior.

• Self-administered surveys were taken by caregivers of adults and children with a confirmed diagnosis of intractable epilepsy.
• Affiliate stigma was defined as perceiving and internalizing negative societal views of the disorder and having a psychological response to those views.
• Caregivers’ psychological burdens were measured using the 30-item Carer’s Assessment of Difficulties Index and the stigma was evaluated with a separate 6-item scale that measured their perceptions of stigma.
• The 136 respondents were mostly white, female, and married.
• Investigators found the link between the stigma of epilepsy and the burden caregivers experienced was stronger among family members caring for adult patients.

Hansena B, Szaflarski M, Bebin EB, Szaflarski JP. Affiliate stigma and caregiver burden in intractable epilepsy. Epilepsy Behav. 2018;85:1-6.

Family caregivers of patients with intractable epilepsy are subject to significant stigma because of societal views about the disorder, according to cross-sectional analysis recently published in Epilepsy and Behavior.

• Self-administered surveys were taken by caregivers of adults and children with a confirmed diagnosis of intractable epilepsy.
• Affiliate stigma was defined as perceiving and internalizing negative societal views of the disorder and having a psychological response to those views.
• Caregivers’ psychological burdens were measured using the 30-item Carer’s Assessment of Difficulties Index and the stigma was evaluated with a separate 6-item scale that measured their perceptions of stigma.
• The 136 respondents were mostly white, female, and married.
• Investigators found the link between the stigma of epilepsy and the burden caregivers experienced was stronger among family members caring for adult patients.

Hansena B, Szaflarski M, Bebin EB, Szaflarski JP. Affiliate stigma and caregiver burden in intractable epilepsy. Epilepsy Behav. 2018;85:1-6.

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.

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.

LOS ANGELES—About one-third of neurologic patients has a high risk of obstructive sleep apnea (OSA), and approximately one-quarter has significant symptoms of insomnia, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The presence of insomnia symptoms is associated with worse neurologic status in movement disorders and epilepsy populations, researchers said.

“Given the high prevalence of sleep disorder symptoms, further investigation into the role of sleep therapies on disease-specific outcomes in neurologic populations is warranted,” said Thapanee Somboon, MD, a neurologist at Prasat Neurological Institute in Bangkok, Thailand, and research fellow at the Cleveland Clinic Sleep Disorders Center, and colleagues.

Analyzing STOP and Insomnia Severity Index Scores

OSA and insomnia are highly prevalent in the general population and may be more common in patients with neurologic conditions. To examine the association between sleep instrument scores and disease-specific outcomes in neurologic populations, Dr. Somboon and colleagues conducted a retrospective analysis of data from 19,052 adult initial visits to the psychiatry, brain tumor, movement disorders, cerebrovascular, and epilepsy centers at the Cleveland Clinic between March 2015 and October 2016.

In all, 7,762 patients had completed the snoring, tiredness, observed apnea, and high blood pressure (STOP) questionnaire, and 8,530 patients had completed the Insomnia Severity Index. A STOP score of 2 or greater predicted a high risk of OSA, and an Insomnia Severity Index score of 15 or greater indicated significant insomnia symptoms.

The crude prevalence of high-risk OSA was 47.9% in the cerebrovascular center, 44.1% in the movement disorders center, 34% in the brain tumor center, 33% in the epilepsy center, 29.8% in the psychiatry center, and 36.7% overall.

The crude prevalence of significant insomnia symptoms was 33.6% in the psychiatry center, 26.1% in the epilepsy center, 20.7% in the brain tumor center, 20% in the movement disorders center, 19.5% in the cerebrovascular center, and 25.5% overall.

Disease-Specific Outcomes

The researchers used regression models to adjust for patients’ age, sex, race, marital status, self-reported sleep duration, income, tobacco use, and comorbid conditions. Multivariate models evaluated the associations between abnormal sleep scores and scores on the Patient Health Questionnaire-9 (PHQ-9; from all centers), Karnofsky Performance Status (from the brain tumor center), Unified Parkinson’s Disease Rating Scale (UPDRS II; from the movement disorders center), modified Rankin Scale (from the cerebrovascular center), and Liverpool Seizure Severity Scale (from the epilepsy center).

Patients with a STOP score of 2 or greater were older, more likely to be male, more likely to be a current or former smoker, had greater PHQ-9 scores, and had more comorbidities.

Patients with Insomnia Severity Index scores of 15 or greater were younger, more likely to be female, more likely to be a current or former smoker, and had a higher prevalence of depression.

OSA and insomnia were significantly associated with PHQ-9 scores. In addition, insomnia symptoms were significantly associated with Liverpool Seizure Severity Scale and UPDRS II scores.

—Jake Remaly

LOS ANGELES—About one-third of neurologic patients has a high risk of obstructive sleep apnea (OSA), and approximately one-quarter has significant symptoms of insomnia, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The presence of insomnia symptoms is associated with worse neurologic status in movement disorders and epilepsy populations, researchers said.

“Given the high prevalence of sleep disorder symptoms, further investigation into the role of sleep therapies on disease-specific outcomes in neurologic populations is warranted,” said Thapanee Somboon, MD, a neurologist at Prasat Neurological Institute in Bangkok, Thailand, and research fellow at the Cleveland Clinic Sleep Disorders Center, and colleagues.

Analyzing STOP and Insomnia Severity Index Scores

OSA and insomnia are highly prevalent in the general population and may be more common in patients with neurologic conditions. To examine the association between sleep instrument scores and disease-specific outcomes in neurologic populations, Dr. Somboon and colleagues conducted a retrospective analysis of data from 19,052 adult initial visits to the psychiatry, brain tumor, movement disorders, cerebrovascular, and epilepsy centers at the Cleveland Clinic between March 2015 and October 2016.

In all, 7,762 patients had completed the snoring, tiredness, observed apnea, and high blood pressure (STOP) questionnaire, and 8,530 patients had completed the Insomnia Severity Index. A STOP score of 2 or greater predicted a high risk of OSA, and an Insomnia Severity Index score of 15 or greater indicated significant insomnia symptoms.

The crude prevalence of high-risk OSA was 47.9% in the cerebrovascular center, 44.1% in the movement disorders center, 34% in the brain tumor center, 33% in the epilepsy center, 29.8% in the psychiatry center, and 36.7% overall.

The crude prevalence of significant insomnia symptoms was 33.6% in the psychiatry center, 26.1% in the epilepsy center, 20.7% in the brain tumor center, 20% in the movement disorders center, 19.5% in the cerebrovascular center, and 25.5% overall.

Disease-Specific Outcomes

The researchers used regression models to adjust for patients’ age, sex, race, marital status, self-reported sleep duration, income, tobacco use, and comorbid conditions. Multivariate models evaluated the associations between abnormal sleep scores and scores on the Patient Health Questionnaire-9 (PHQ-9; from all centers), Karnofsky Performance Status (from the brain tumor center), Unified Parkinson’s Disease Rating Scale (UPDRS II; from the movement disorders center), modified Rankin Scale (from the cerebrovascular center), and Liverpool Seizure Severity Scale (from the epilepsy center).

Patients with a STOP score of 2 or greater were older, more likely to be male, more likely to be a current or former smoker, had greater PHQ-9 scores, and had more comorbidities.

Patients with Insomnia Severity Index scores of 15 or greater were younger, more likely to be female, more likely to be a current or former smoker, and had a higher prevalence of depression.

OSA and insomnia were significantly associated with PHQ-9 scores. In addition, insomnia symptoms were significantly associated with Liverpool Seizure Severity Scale and UPDRS II scores.

—Jake Remaly

LOS ANGELES—About one-third of neurologic patients has a high risk of obstructive sleep apnea (OSA), and approximately one-quarter has significant symptoms of insomnia, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The presence of insomnia symptoms is associated with worse neurologic status in movement disorders and epilepsy populations, researchers said.

“Given the high prevalence of sleep disorder symptoms, further investigation into the role of sleep therapies on disease-specific outcomes in neurologic populations is warranted,” said Thapanee Somboon, MD, a neurologist at Prasat Neurological Institute in Bangkok, Thailand, and research fellow at the Cleveland Clinic Sleep Disorders Center, and colleagues.

Analyzing STOP and Insomnia Severity Index Scores

OSA and insomnia are highly prevalent in the general population and may be more common in patients with neurologic conditions. To examine the association between sleep instrument scores and disease-specific outcomes in neurologic populations, Dr. Somboon and colleagues conducted a retrospective analysis of data from 19,052 adult initial visits to the psychiatry, brain tumor, movement disorders, cerebrovascular, and epilepsy centers at the Cleveland Clinic between March 2015 and October 2016.

In all, 7,762 patients had completed the snoring, tiredness, observed apnea, and high blood pressure (STOP) questionnaire, and 8,530 patients had completed the Insomnia Severity Index. A STOP score of 2 or greater predicted a high risk of OSA, and an Insomnia Severity Index score of 15 or greater indicated significant insomnia symptoms.

The crude prevalence of high-risk OSA was 47.9% in the cerebrovascular center, 44.1% in the movement disorders center, 34% in the brain tumor center, 33% in the epilepsy center, 29.8% in the psychiatry center, and 36.7% overall.

The crude prevalence of significant insomnia symptoms was 33.6% in the psychiatry center, 26.1% in the epilepsy center, 20.7% in the brain tumor center, 20% in the movement disorders center, 19.5% in the cerebrovascular center, and 25.5% overall.

Disease-Specific Outcomes

The researchers used regression models to adjust for patients’ age, sex, race, marital status, self-reported sleep duration, income, tobacco use, and comorbid conditions. Multivariate models evaluated the associations between abnormal sleep scores and scores on the Patient Health Questionnaire-9 (PHQ-9; from all centers), Karnofsky Performance Status (from the brain tumor center), Unified Parkinson’s Disease Rating Scale (UPDRS II; from the movement disorders center), modified Rankin Scale (from the cerebrovascular center), and Liverpool Seizure Severity Scale (from the epilepsy center).

Patients with a STOP score of 2 or greater were older, more likely to be male, more likely to be a current or former smoker, had greater PHQ-9 scores, and had more comorbidities.

Patients with Insomnia Severity Index scores of 15 or greater were younger, more likely to be female, more likely to be a current or former smoker, and had a higher prevalence of depression.

OSA and insomnia were significantly associated with PHQ-9 scores. In addition, insomnia symptoms were significantly associated with Liverpool Seizure Severity Scale and UPDRS II scores.

—Jake Remaly

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.”

The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.

The approval, the first for a marijuana-derived pharmaceutical product, falls in line with the unanimous recommendation of an FDA advisory panel to approve cannabidiol oral solution (CBD-OS) for the treatment of Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years of age and older.

“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.

However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”

The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.

“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.

After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.

Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.

A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.

In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.

The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
 

[email protected]

The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.

The approval, the first for a marijuana-derived pharmaceutical product, falls in line with the unanimous recommendation of an FDA advisory panel to approve cannabidiol oral solution (CBD-OS) for the treatment of Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years of age and older.

“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.

However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”

The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.

“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.

After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.

Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.

A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.

In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.

The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
 

[email protected]

The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.

The approval, the first for a marijuana-derived pharmaceutical product, falls in line with the unanimous recommendation of an FDA advisory panel to approve cannabidiol oral solution (CBD-OS) for the treatment of Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years of age and older.

“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.

However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”

The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.

“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.

After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.

Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.

A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.

In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.

The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
 

[email protected]