Epilepsy Resource Center

NEW ORLEANS – Cannabis oil extract with a 20:1 ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) may reduce seizures in children and adults with treatment-resistant epilepsy, but about a quarter of patients develop tolerance, according to a study presented at the annual meeting of the American Epilepsy Society.

“CBD is a good option for children and adults with certain kinds of epilepsy, but as with antiepileptic drugs, it can become less effective over time, and the dose may need to be increased to manage the seizures,” said Shimrit Uliel-Sibony, MD, lead author of the study and head of the pediatric epilepsy service at Tel Aviv Sourasky Medical Center’s Dana-Dwek Children’s Hospital.

Prior studies have found that the efficacy of cannabinoids may wane when used for pain management. Efficacy also declines in animals with seizures.

To assess the tolerance rate of cannabinoids in the treatment of children and adults with epilepsy, researchers in Israel conducted a prospective review of 92 consecutive patients with treatment-resistant epilepsy. Patients were aged 1-37 years (mean age, 11.8 years) and were treated with cannabis oil extract during March 1, 2014–Dec. 31, 2017. The researchers defined tolerance as the need to increase the dose by at least 30% following a reduction in efficacy, or a more than 30% reduction in treatment response.

The patients had various forms of epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, and epilepsy caused by stroke) and used cannabis oil extract for an average of 19.8 months. Of the 84 patients included in the tolerance analysis, 21 patients (25%) developed tolerance after an average of 7.3 months (range, 1-24 months) at an average dose of 12.6 mg/kg per day. After patients with tolerance received an increased dose, 4 patients returned to their previous response levels, and 10 patients had a response that was “satisfying but less than [the] prior response level,” Dr. Uliel-Sibony and colleagues said.

About a third of patients discontinued treatment because of side effects or lack of efficacy. Side effects included sleepiness, nausea, decreased appetite, and vomiting. In addition, seizures worsened in two patients, and one patient had signs of psychosis; treatment was stopped immediately in those three patients.

The investigators had no disclosures and received no funding for this study.

jremaly@mdedge.com

SOURCE: Uliel-Sibony S et al., AES 2018, Abstract 2.233.

NEW ORLEANS – Cannabis oil extract with a 20:1 ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) may reduce seizures in children and adults with treatment-resistant epilepsy, but about a quarter of patients develop tolerance, according to a study presented at the annual meeting of the American Epilepsy Society.

“CBD is a good option for children and adults with certain kinds of epilepsy, but as with antiepileptic drugs, it can become less effective over time, and the dose may need to be increased to manage the seizures,” said Shimrit Uliel-Sibony, MD, lead author of the study and head of the pediatric epilepsy service at Tel Aviv Sourasky Medical Center’s Dana-Dwek Children’s Hospital.

Prior studies have found that the efficacy of cannabinoids may wane when used for pain management. Efficacy also declines in animals with seizures.

To assess the tolerance rate of cannabinoids in the treatment of children and adults with epilepsy, researchers in Israel conducted a prospective review of 92 consecutive patients with treatment-resistant epilepsy. Patients were aged 1-37 years (mean age, 11.8 years) and were treated with cannabis oil extract during March 1, 2014–Dec. 31, 2017. The researchers defined tolerance as the need to increase the dose by at least 30% following a reduction in efficacy, or a more than 30% reduction in treatment response.

The patients had various forms of epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, and epilepsy caused by stroke) and used cannabis oil extract for an average of 19.8 months. Of the 84 patients included in the tolerance analysis, 21 patients (25%) developed tolerance after an average of 7.3 months (range, 1-24 months) at an average dose of 12.6 mg/kg per day. After patients with tolerance received an increased dose, 4 patients returned to their previous response levels, and 10 patients had a response that was “satisfying but less than [the] prior response level,” Dr. Uliel-Sibony and colleagues said.

About a third of patients discontinued treatment because of side effects or lack of efficacy. Side effects included sleepiness, nausea, decreased appetite, and vomiting. In addition, seizures worsened in two patients, and one patient had signs of psychosis; treatment was stopped immediately in those three patients.

The investigators had no disclosures and received no funding for this study.

jremaly@mdedge.com

SOURCE: Uliel-Sibony S et al., AES 2018, Abstract 2.233.

NEW ORLEANS – Cannabis oil extract with a 20:1 ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) may reduce seizures in children and adults with treatment-resistant epilepsy, but about a quarter of patients develop tolerance, according to a study presented at the annual meeting of the American Epilepsy Society.

“CBD is a good option for children and adults with certain kinds of epilepsy, but as with antiepileptic drugs, it can become less effective over time, and the dose may need to be increased to manage the seizures,” said Shimrit Uliel-Sibony, MD, lead author of the study and head of the pediatric epilepsy service at Tel Aviv Sourasky Medical Center’s Dana-Dwek Children’s Hospital.

Prior studies have found that the efficacy of cannabinoids may wane when used for pain management. Efficacy also declines in animals with seizures.

To assess the tolerance rate of cannabinoids in the treatment of children and adults with epilepsy, researchers in Israel conducted a prospective review of 92 consecutive patients with treatment-resistant epilepsy. Patients were aged 1-37 years (mean age, 11.8 years) and were treated with cannabis oil extract during March 1, 2014–Dec. 31, 2017. The researchers defined tolerance as the need to increase the dose by at least 30% following a reduction in efficacy, or a more than 30% reduction in treatment response.

The patients had various forms of epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, and epilepsy caused by stroke) and used cannabis oil extract for an average of 19.8 months. Of the 84 patients included in the tolerance analysis, 21 patients (25%) developed tolerance after an average of 7.3 months (range, 1-24 months) at an average dose of 12.6 mg/kg per day. After patients with tolerance received an increased dose, 4 patients returned to their previous response levels, and 10 patients had a response that was “satisfying but less than [the] prior response level,” Dr. Uliel-Sibony and colleagues said.

About a third of patients discontinued treatment because of side effects or lack of efficacy. Side effects included sleepiness, nausea, decreased appetite, and vomiting. In addition, seizures worsened in two patients, and one patient had signs of psychosis; treatment was stopped immediately in those three patients.

The investigators had no disclosures and received no funding for this study.

jremaly@mdedge.com

SOURCE: Uliel-Sibony S et al., AES 2018, Abstract 2.233.

Two clinical parameters measurable at seizure onset appear to predict a return to baseline after prolonged status epilepticus (SE), based on a study of patients who presented to a single, tertiary academic medical center over a 12-year period.

Absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index were the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, the researchers found. However, the research fell short of developing a model for identifying patients at risk for prolonged SE.

“These findings are of great clinical importance, as up to now, clinicians have had no reliable prediction tools to direct decisions regarding the level of care with progressive SE duration. Early and reliable identification of patients with potential favorable outcome despite having SE for several days is of utmost clinical importance, as this insight may urge clinicians to intensify treatment rather than consider care withdrawal as systemic and neurologic sequelae increase, and chances of SE termination decrease over time,” first author Raoul C. Sutter, MD, of University Hospital Basel (Switzerland), and his colleagues wrote about their findings in Epilepsia.

The researchers identified 467 adult patients with prolonged SE at University Hospital Basel during 2005-2016 – excluding those with SE as a consequence of hypoxic‐ischemic brain injury – who had a median age of 66.7 years and median SE duration of 1 day. While 11.8% of patients died in the hospital and 12.4% at 30 days after SE onset, 40.9% made a complete neurologic and functional recovery to their premorbid status.

There were significant differences in in-hospital outcomes between patients with different SE durations. For example, rates of returning to baseline differed significantly at 55.6% of those with a SE duration of 0-12 hours, 36.8% with 12-24 hours’ duration, 34.6% with 24-48 hours’ duration, and 25.5% with more than 48 hours.

A multivariable regression model identified absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index as the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, and both remained significant predictors after adjustment for use of anesthetics and vasopressors. These predictors of a return to baseline after prolonged SE remained significant after excluding patients who died. This two-variable prediction model had an area under the receiver operating curve (AUROC) of 0.82, “indicating good discrimination,” and an AUROC of 0.76 following cross-validation.

The investigators also sought to develop a model to identify patients at risk for prolonged SE, but the model showed relatively poor discriminative ability with AUROCs of just 0.67-0.72 for predicting no termination of SE within 12, 24, or 48 hours. “Our attempt to generate a highly reliable prediction model for early recognition of patients at increased risk for developing prolonged SE failed, as demonstrated by the rather small AUROC and the fact that sensitivity analyses after exclusion of patients who died revealed inconsistent association of the identified predictors,” they wrote.

Prior reports identified younger age, absence of acute brain lesions at presentation, and the absence of multiple concomitant medical problems as factors associated with favorable outcome after prolonged SE, but “none of the studies performed multivariable regression models and generated or tested predictions models in this context,” they noted.

The authors cautioned that “although internal cross-validation of the final prediction model indicated adequate performance [based on an AUROC of 0.76], further external validation of our prediction model is warranted before our prediction model can be implemented and used for decision making in daily clinical practice.”

Some authors reported receiving research, travel, and/or personal grants or speaker fees from companies marketing antiepileptic drugs, such as UCB, Eisai, and GlaxoSmithKline.

jevans@mdedge.com

SOURCE: Sutter RC et al. Epilepsia. 2018 Nov 22. doi: 10.1111/epi.14603

Two clinical parameters measurable at seizure onset appear to predict a return to baseline after prolonged status epilepticus (SE), based on a study of patients who presented to a single, tertiary academic medical center over a 12-year period.

Absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index were the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, the researchers found. However, the research fell short of developing a model for identifying patients at risk for prolonged SE.

“These findings are of great clinical importance, as up to now, clinicians have had no reliable prediction tools to direct decisions regarding the level of care with progressive SE duration. Early and reliable identification of patients with potential favorable outcome despite having SE for several days is of utmost clinical importance, as this insight may urge clinicians to intensify treatment rather than consider care withdrawal as systemic and neurologic sequelae increase, and chances of SE termination decrease over time,” first author Raoul C. Sutter, MD, of University Hospital Basel (Switzerland), and his colleagues wrote about their findings in Epilepsia.

The researchers identified 467 adult patients with prolonged SE at University Hospital Basel during 2005-2016 – excluding those with SE as a consequence of hypoxic‐ischemic brain injury – who had a median age of 66.7 years and median SE duration of 1 day. While 11.8% of patients died in the hospital and 12.4% at 30 days after SE onset, 40.9% made a complete neurologic and functional recovery to their premorbid status.

There were significant differences in in-hospital outcomes between patients with different SE durations. For example, rates of returning to baseline differed significantly at 55.6% of those with a SE duration of 0-12 hours, 36.8% with 12-24 hours’ duration, 34.6% with 24-48 hours’ duration, and 25.5% with more than 48 hours.

A multivariable regression model identified absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index as the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, and both remained significant predictors after adjustment for use of anesthetics and vasopressors. These predictors of a return to baseline after prolonged SE remained significant after excluding patients who died. This two-variable prediction model had an area under the receiver operating curve (AUROC) of 0.82, “indicating good discrimination,” and an AUROC of 0.76 following cross-validation.

The investigators also sought to develop a model to identify patients at risk for prolonged SE, but the model showed relatively poor discriminative ability with AUROCs of just 0.67-0.72 for predicting no termination of SE within 12, 24, or 48 hours. “Our attempt to generate a highly reliable prediction model for early recognition of patients at increased risk for developing prolonged SE failed, as demonstrated by the rather small AUROC and the fact that sensitivity analyses after exclusion of patients who died revealed inconsistent association of the identified predictors,” they wrote.

Prior reports identified younger age, absence of acute brain lesions at presentation, and the absence of multiple concomitant medical problems as factors associated with favorable outcome after prolonged SE, but “none of the studies performed multivariable regression models and generated or tested predictions models in this context,” they noted.

The authors cautioned that “although internal cross-validation of the final prediction model indicated adequate performance [based on an AUROC of 0.76], further external validation of our prediction model is warranted before our prediction model can be implemented and used for decision making in daily clinical practice.”

Some authors reported receiving research, travel, and/or personal grants or speaker fees from companies marketing antiepileptic drugs, such as UCB, Eisai, and GlaxoSmithKline.

jevans@mdedge.com

SOURCE: Sutter RC et al. Epilepsia. 2018 Nov 22. doi: 10.1111/epi.14603

Two clinical parameters measurable at seizure onset appear to predict a return to baseline after prolonged status epilepticus (SE), based on a study of patients who presented to a single, tertiary academic medical center over a 12-year period.

Absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index were the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, the researchers found. However, the research fell short of developing a model for identifying patients at risk for prolonged SE.

“These findings are of great clinical importance, as up to now, clinicians have had no reliable prediction tools to direct decisions regarding the level of care with progressive SE duration. Early and reliable identification of patients with potential favorable outcome despite having SE for several days is of utmost clinical importance, as this insight may urge clinicians to intensify treatment rather than consider care withdrawal as systemic and neurologic sequelae increase, and chances of SE termination decrease over time,” first author Raoul C. Sutter, MD, of University Hospital Basel (Switzerland), and his colleagues wrote about their findings in Epilepsia.

The researchers identified 467 adult patients with prolonged SE at University Hospital Basel during 2005-2016 – excluding those with SE as a consequence of hypoxic‐ischemic brain injury – who had a median age of 66.7 years and median SE duration of 1 day. While 11.8% of patients died in the hospital and 12.4% at 30 days after SE onset, 40.9% made a complete neurologic and functional recovery to their premorbid status.

There were significant differences in in-hospital outcomes between patients with different SE durations. For example, rates of returning to baseline differed significantly at 55.6% of those with a SE duration of 0-12 hours, 36.8% with 12-24 hours’ duration, 34.6% with 24-48 hours’ duration, and 25.5% with more than 48 hours.

A multivariable regression model identified absence of nonconvulsive SE with coma and a decreasing Charlson Comorbidity Index as the only independent predictors for return to baseline in patients with SE duration greater than 48 hours, and both remained significant predictors after adjustment for use of anesthetics and vasopressors. These predictors of a return to baseline after prolonged SE remained significant after excluding patients who died. This two-variable prediction model had an area under the receiver operating curve (AUROC) of 0.82, “indicating good discrimination,” and an AUROC of 0.76 following cross-validation.

The investigators also sought to develop a model to identify patients at risk for prolonged SE, but the model showed relatively poor discriminative ability with AUROCs of just 0.67-0.72 for predicting no termination of SE within 12, 24, or 48 hours. “Our attempt to generate a highly reliable prediction model for early recognition of patients at increased risk for developing prolonged SE failed, as demonstrated by the rather small AUROC and the fact that sensitivity analyses after exclusion of patients who died revealed inconsistent association of the identified predictors,” they wrote.

Prior reports identified younger age, absence of acute brain lesions at presentation, and the absence of multiple concomitant medical problems as factors associated with favorable outcome after prolonged SE, but “none of the studies performed multivariable regression models and generated or tested predictions models in this context,” they noted.

The authors cautioned that “although internal cross-validation of the final prediction model indicated adequate performance [based on an AUROC of 0.76], further external validation of our prediction model is warranted before our prediction model can be implemented and used for decision making in daily clinical practice.”

Some authors reported receiving research, travel, and/or personal grants or speaker fees from companies marketing antiepileptic drugs, such as UCB, Eisai, and GlaxoSmithKline.

jevans@mdedge.com

SOURCE: Sutter RC et al. Epilepsia. 2018 Nov 22. doi: 10.1111/epi.14603

Although ambulatory EEGs (aEEGs) can help distinguish epileptic attacks from non-epileptic attacks, they have their limitations. A recent retrospective review of EEG procedure notes from the Stanford Comprehensive Epilepsy Center has found that they rarely yield useful information beyond 24 hours duration.

• Stanford researchers analyzed 358 adult aEEG readings from 2010 to 2017 and found epileptiform discharges or epileptic seizures in 101 of the readings (28%).
• The analysis compared detection rates for 20-30 hours, 30-50 hours, and 50-76 hours and found little difference.
• Epilepsy seizures were observed in 11%, 7%, and 10% respectively for the 3 duration periods.
• An analysis of the epileptiform abnormalities revealed no significant differences in detection rates for the 3 duration periods.
• Among aEEGs that were ordered to characterize suspected events, however, 72 hours was the best option because it generated a higher rate of capture.

Kuo J, Lee-Messer C, Le S. Optimal recording duration of ambulatory EEG (aEEG). Epilepsy Res. 2018;149:9-12.

Although ambulatory EEGs (aEEGs) can help distinguish epileptic attacks from non-epileptic attacks, they have their limitations. A recent retrospective review of EEG procedure notes from the Stanford Comprehensive Epilepsy Center has found that they rarely yield useful information beyond 24 hours duration.

• Stanford researchers analyzed 358 adult aEEG readings from 2010 to 2017 and found epileptiform discharges or epileptic seizures in 101 of the readings (28%).
• The analysis compared detection rates for 20-30 hours, 30-50 hours, and 50-76 hours and found little difference.
• Epilepsy seizures were observed in 11%, 7%, and 10% respectively for the 3 duration periods.
• An analysis of the epileptiform abnormalities revealed no significant differences in detection rates for the 3 duration periods.
• Among aEEGs that were ordered to characterize suspected events, however, 72 hours was the best option because it generated a higher rate of capture.

Kuo J, Lee-Messer C, Le S. Optimal recording duration of ambulatory EEG (aEEG). Epilepsy Res. 2018;149:9-12.

Although ambulatory EEGs (aEEGs) can help distinguish epileptic attacks from non-epileptic attacks, they have their limitations. A recent retrospective review of EEG procedure notes from the Stanford Comprehensive Epilepsy Center has found that they rarely yield useful information beyond 24 hours duration.

• Stanford researchers analyzed 358 adult aEEG readings from 2010 to 2017 and found epileptiform discharges or epileptic seizures in 101 of the readings (28%).
• The analysis compared detection rates for 20-30 hours, 30-50 hours, and 50-76 hours and found little difference.
• Epilepsy seizures were observed in 11%, 7%, and 10% respectively for the 3 duration periods.
• An analysis of the epileptiform abnormalities revealed no significant differences in detection rates for the 3 duration periods.
• Among aEEGs that were ordered to characterize suspected events, however, 72 hours was the best option because it generated a higher rate of capture.

Kuo J, Lee-Messer C, Le S. Optimal recording duration of ambulatory EEG (aEEG). Epilepsy Res. 2018;149:9-12.

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Among children who have had surgical resection of epileptic lesions, it may be wise to continue postoperative invasive monitoring, suggests this investigation of 71 patients published in Epilepsy Research.

• A retrospective analysis of 5 patients with MRI-negative epilepsy and 66 patients with MRI-identified neocortical lesions, post-resection invasive monitoring yielded positive outcomes in 86%.
• In 55 of 71 patients, post-resection monitoring resulted in additional resections.
• Postop monitoring detected clinical seizures at the resection margins, subclinical seizures and interictal discharges at the resection margins, and both clinical and subclinical seizures that indicated a new epileptogenic focus.

Hidalgo ET, Frankel HG, Rodriguez C, et al. Invasive monitoring after resection of epileptogenic neocortical lesions in multi-staged epilepsy surgery in children. Epilepsy Res. 2018; 148:48-54.   

Among children who have had surgical resection of epileptic lesions, it may be wise to continue postoperative invasive monitoring, suggests this investigation of 71 patients published in Epilepsy Research.

• A retrospective analysis of 5 patients with MRI-negative epilepsy and 66 patients with MRI-identified neocortical lesions, post-resection invasive monitoring yielded positive outcomes in 86%.
• In 55 of 71 patients, post-resection monitoring resulted in additional resections.
• Postop monitoring detected clinical seizures at the resection margins, subclinical seizures and interictal discharges at the resection margins, and both clinical and subclinical seizures that indicated a new epileptogenic focus.

Hidalgo ET, Frankel HG, Rodriguez C, et al. Invasive monitoring after resection of epileptogenic neocortical lesions in multi-staged epilepsy surgery in children. Epilepsy Res. 2018; 148:48-54.   

Among children who have had surgical resection of epileptic lesions, it may be wise to continue postoperative invasive monitoring, suggests this investigation of 71 patients published in Epilepsy Research.

• A retrospective analysis of 5 patients with MRI-negative epilepsy and 66 patients with MRI-identified neocortical lesions, post-resection invasive monitoring yielded positive outcomes in 86%.
• In 55 of 71 patients, post-resection monitoring resulted in additional resections.
• Postop monitoring detected clinical seizures at the resection margins, subclinical seizures and interictal discharges at the resection margins, and both clinical and subclinical seizures that indicated a new epileptogenic focus.

Hidalgo ET, Frankel HG, Rodriguez C, et al. Invasive monitoring after resection of epileptogenic neocortical lesions in multi-staged epilepsy surgery in children. Epilepsy Res. 2018; 148:48-54.   

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Among people with Alzheimer Disease, the risk of developing a stroke is significantly greater if they are using antiepileptic drugs, according to a large study published in the Journal of the American Heart Association.

• The Medication Use and Alzheimer’s Disease cohort, which includes all the people in Finland who have been clinically diagnosed with Alzheimer disease (70,718) from 2005 to 2011, was analyzed to look for a correlation between the disease and antiepileptic drug use.
• Patients who had used the medications were about 37% more likely to have experienced a stroke, compared to nondrug users (hazard ratio [HR], 1.37).
• The likelihood of having a stroke in this patient population was greatest during the first 3 months of taking antiepileptic medication (HR, 2.36).
• The association between drug use and ischemic stroke was less than that observed between drug use and hemorrhagic stroke (HR, 1.34 vs 1.44).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People with Alzheimer Disease: A Matched Cohort Study. J Am Heart Assoc. 2018; 7: e009742. DOI: 10.1161/JAHA.118.009742.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.

Standard depth invasive electrodes are typically used to precisely locate areas of the brain that are responsible for seizures in patients with medically refractory epilepsy, but a recent analysis suggests that hybrid depth microwire electrodes may be just as effective and just as safe.

• Investigators at Cedars-Sinai Medical Center reviewed 53 cases of refractory epilepsy who had surgery between 2006 and 2017.
• The analysis included 555 electrodes and revealed a complication rate of 2.3% per electrode and a per case rate of 20.8%; no infections or deaths were reported.
• The researchers did not uncover a difference in complication rates between standard and hybrid depth electrodes.
• Hybrid depth electrodes were as reliable as standard electrodes in pinpointing seizure onset zones.

Carlson AA, Rutishauser U, Mamelak AN. Safety and utility of hybrid depth electrodes for seizure localization and single-unit neuronal recording [published online ahead of print Oct 16, 2018]. Stereotact Funct Neurosurg.

Children with autism who also have an abnormal EEG or epilepsy are more likely to experience problems with developmental and adaptive functioning, according to an analysis of 443 patients with autism spectrum disorder (ASD).

• The medical records of children with autism were reviewed by researchers at Cincinnati Children’s Hospital Medical Center.
• The children were divided into 3 categories: those with ASD, no epilepsy, and abnormal EEG results; those with ASD, no epilepsy, and normal EEG; and those with ASD and epilepsy.
• Among 372 patients with ASD without epilepsy, 25.5% had an abnormal EEG; these patients were more likely to have more impaired adaptive functioning when compared to patients with normal EEG readings.
• Children with abnormal EEG readings presented with similar abnormalities to the group with epilepsy.
• Patients with epilepsy had lower scores on all the tests that measure developmental and adaptive functioning, when compared to those with normal EEG readings.

Capal JK, Carosella C, Corbin E, et al. EEG endophenotypes in autism spectrum disorder [published online ahead of print Oct 17, 2018]. Epilepsy Behav.  

Children with autism who also have an abnormal EEG or epilepsy are more likely to experience problems with developmental and adaptive functioning, according to an analysis of 443 patients with autism spectrum disorder (ASD).

• The medical records of children with autism were reviewed by researchers at Cincinnati Children’s Hospital Medical Center.
• The children were divided into 3 categories: those with ASD, no epilepsy, and abnormal EEG results; those with ASD, no epilepsy, and normal EEG; and those with ASD and epilepsy.
• Among 372 patients with ASD without epilepsy, 25.5% had an abnormal EEG; these patients were more likely to have more impaired adaptive functioning when compared to patients with normal EEG readings.
• Children with abnormal EEG readings presented with similar abnormalities to the group with epilepsy.
• Patients with epilepsy had lower scores on all the tests that measure developmental and adaptive functioning, when compared to those with normal EEG readings.

Capal JK, Carosella C, Corbin E, et al. EEG endophenotypes in autism spectrum disorder [published online ahead of print Oct 17, 2018]. Epilepsy Behav.  

Children with autism who also have an abnormal EEG or epilepsy are more likely to experience problems with developmental and adaptive functioning, according to an analysis of 443 patients with autism spectrum disorder (ASD).

• The medical records of children with autism were reviewed by researchers at Cincinnati Children’s Hospital Medical Center.
• The children were divided into 3 categories: those with ASD, no epilepsy, and abnormal EEG results; those with ASD, no epilepsy, and normal EEG; and those with ASD and epilepsy.
• Among 372 patients with ASD without epilepsy, 25.5% had an abnormal EEG; these patients were more likely to have more impaired adaptive functioning when compared to patients with normal EEG readings.
• Children with abnormal EEG readings presented with similar abnormalities to the group with epilepsy.
• Patients with epilepsy had lower scores on all the tests that measure developmental and adaptive functioning, when compared to those with normal EEG readings.

Capal JK, Carosella C, Corbin E, et al. EEG endophenotypes in autism spectrum disorder [published online ahead of print Oct 17, 2018]. Epilepsy Behav.  

WASHINGTON, DC—The Drug Enforcement Administration (DEA) has reclassified Epidiolex, an oral cannabidiol (CBD) solution, from Schedule I to Schedule V, the lowest category of scheduled substances. The FDA approved Epidiolex earlier this year for the adjunctive treatment of seizures in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome aged 2 and older. The DEA’s action paves the way for the manufacturer, GW Pharmaceuticals, to begin marketing Epidiolex, which is expected to be available in the United States this fall.

The DEA’s final rescheduling order is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinol (THC). In practice, this means that the rescheduling currently applies only to Epidiolex, since this is the only formulation of CBD that has received FDA approval.

A Low Potential for Abuse

“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS and Dravet syndrome, two of the most debilitating forms of epilepsy, can access this important new treatment option through their physicians,” said GW Pharmaceutical’s Chief Executive Officer Justin Gover in a statement.

During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndrome, the FDA and GW Pharmaceuticals concluded that the potential to abuse CBD was low, since it does not contain THC, the primary psychoactive component of cannabis.

All other marijuana products are currently classified as Schedule I, along with illegal substances such as heroin and cocaine.

An Established Medical Use

Epidiolex had received fast track and rare pediatric designations from the FDA for LGS and Dravet syndrome; the approval was based on three pivotal randomized, double-blind, placebo-controlled clinical trials. The drug met its primary end point of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and those with Dravet syndrome.

Safety evaluations assessed data from 1,756 patients and found that the 20 deaths seen during the study period were not clearly linked to Epidiolex and may be expected for children with severe seizure disorders.

In supplementary information accompanying the order, the DEA’s Acting Administrator Uttam Dhillon noted that the FDA’s approval of Epidiolex means that “it has a currently accepted medical use in treatment for purposes of the Controlled Substances Act [CSA]. Accordingly, Epidiolex no longer meets the criteria for placement in Schedule I of the CSA.” Schedule I drugs do not have a currently accepted medical use.

Schedule V drugs, according to the DEA, are defined as “drugs with lower potential for abuse than Schedule IV and [that] consist of preparations containing limited quantities of certain narcotics.” Other Schedule V drugs include cough medicine with less than 200 mg of codeine or per 100 mL, antidiarrheal medications, pregabalin, and the antiepileptic drugs brivaracetam and lacosamide. “Schedule V drugs represent the least potential for abuse,” according to the DEA.

Initial dosing recommendations for Epidiolex are to titrate to a dose of 10 mg/kg/day. Dose adjustments to 20 mg/kg/day are permissible, depending on clinical response and tolerability. The manufacturer has submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of tuberous sclerosis complex.

—Kari Oakes

WASHINGTON, DC—The Drug Enforcement Administration (DEA) has reclassified Epidiolex, an oral cannabidiol (CBD) solution, from Schedule I to Schedule V, the lowest category of scheduled substances. The FDA approved Epidiolex earlier this year for the adjunctive treatment of seizures in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome aged 2 and older. The DEA’s action paves the way for the manufacturer, GW Pharmaceuticals, to begin marketing Epidiolex, which is expected to be available in the United States this fall.

The DEA’s final rescheduling order is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinol (THC). In practice, this means that the rescheduling currently applies only to Epidiolex, since this is the only formulation of CBD that has received FDA approval.

A Low Potential for Abuse

“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS and Dravet syndrome, two of the most debilitating forms of epilepsy, can access this important new treatment option through their physicians,” said GW Pharmaceutical’s Chief Executive Officer Justin Gover in a statement.

During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndrome, the FDA and GW Pharmaceuticals concluded that the potential to abuse CBD was low, since it does not contain THC, the primary psychoactive component of cannabis.

All other marijuana products are currently classified as Schedule I, along with illegal substances such as heroin and cocaine.

An Established Medical Use

Epidiolex had received fast track and rare pediatric designations from the FDA for LGS and Dravet syndrome; the approval was based on three pivotal randomized, double-blind, placebo-controlled clinical trials. The drug met its primary end point of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and those with Dravet syndrome.

Safety evaluations assessed data from 1,756 patients and found that the 20 deaths seen during the study period were not clearly linked to Epidiolex and may be expected for children with severe seizure disorders.

In supplementary information accompanying the order, the DEA’s Acting Administrator Uttam Dhillon noted that the FDA’s approval of Epidiolex means that “it has a currently accepted medical use in treatment for purposes of the Controlled Substances Act [CSA]. Accordingly, Epidiolex no longer meets the criteria for placement in Schedule I of the CSA.” Schedule I drugs do not have a currently accepted medical use.

Schedule V drugs, according to the DEA, are defined as “drugs with lower potential for abuse than Schedule IV and [that] consist of preparations containing limited quantities of certain narcotics.” Other Schedule V drugs include cough medicine with less than 200 mg of codeine or per 100 mL, antidiarrheal medications, pregabalin, and the antiepileptic drugs brivaracetam and lacosamide. “Schedule V drugs represent the least potential for abuse,” according to the DEA.

Initial dosing recommendations for Epidiolex are to titrate to a dose of 10 mg/kg/day. Dose adjustments to 20 mg/kg/day are permissible, depending on clinical response and tolerability. The manufacturer has submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of tuberous sclerosis complex.

—Kari Oakes

WASHINGTON, DC—The Drug Enforcement Administration (DEA) has reclassified Epidiolex, an oral cannabidiol (CBD) solution, from Schedule I to Schedule V, the lowest category of scheduled substances. The FDA approved Epidiolex earlier this year for the adjunctive treatment of seizures in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome aged 2 and older. The DEA’s action paves the way for the manufacturer, GW Pharmaceuticals, to begin marketing Epidiolex, which is expected to be available in the United States this fall.

The DEA’s final rescheduling order is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinol (THC). In practice, this means that the rescheduling currently applies only to Epidiolex, since this is the only formulation of CBD that has received FDA approval.

A Low Potential for Abuse

“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS and Dravet syndrome, two of the most debilitating forms of epilepsy, can access this important new treatment option through their physicians,” said GW Pharmaceutical’s Chief Executive Officer Justin Gover in a statement.

During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndrome, the FDA and GW Pharmaceuticals concluded that the potential to abuse CBD was low, since it does not contain THC, the primary psychoactive component of cannabis.

All other marijuana products are currently classified as Schedule I, along with illegal substances such as heroin and cocaine.

An Established Medical Use

Epidiolex had received fast track and rare pediatric designations from the FDA for LGS and Dravet syndrome; the approval was based on three pivotal randomized, double-blind, placebo-controlled clinical trials. The drug met its primary end point of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and those with Dravet syndrome.

Safety evaluations assessed data from 1,756 patients and found that the 20 deaths seen during the study period were not clearly linked to Epidiolex and may be expected for children with severe seizure disorders.

In supplementary information accompanying the order, the DEA’s Acting Administrator Uttam Dhillon noted that the FDA’s approval of Epidiolex means that “it has a currently accepted medical use in treatment for purposes of the Controlled Substances Act [CSA]. Accordingly, Epidiolex no longer meets the criteria for placement in Schedule I of the CSA.” Schedule I drugs do not have a currently accepted medical use.

Schedule V drugs, according to the DEA, are defined as “drugs with lower potential for abuse than Schedule IV and [that] consist of preparations containing limited quantities of certain narcotics.” Other Schedule V drugs include cough medicine with less than 200 mg of codeine or per 100 mL, antidiarrheal medications, pregabalin, and the antiepileptic drugs brivaracetam and lacosamide. “Schedule V drugs represent the least potential for abuse,” according to the DEA.

Initial dosing recommendations for Epidiolex are to titrate to a dose of 10 mg/kg/day. Dose adjustments to 20 mg/kg/day are permissible, depending on clinical response and tolerability. The manufacturer has submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of tuberous sclerosis complex.

—Kari Oakes

CHICAGO—Use of rapid sequence MRI in the evaluation of neonates with seizures and no hypoxic-ischemic encephalopathy (HIE) is associated with reduced number of CT and MRI scans and similar length of hospital stay and cost, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. “The potential reduction in radiation and sedation exposure associated with CTs and regular MRIs makes rapid sequence MRI an attractive imaging modality in this population,” said Theresa M. Czech, MD, and Andrea C. Pardo, MD, attending physicians at Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. Czech is an Instructor in Pediatrics, and Dr. Pardo is an Assistant Professor of Pediatrics, both at Northwestern University Feinberg School of Medicine in Chicago.

Neurologists routinely use brain imaging to identify the etiologies of neonatal seizures. Rapid sequence MRI “can reduce the risk of radiation associated with CT or the need for procedural sedation associated with regular MRIs,” said Drs. Czech and Pardo. “Our goal was to determine whether the implementation of a protocol recommending the use of rapid sequence MRI was associated with increased efficiency in the evaluation of neonates with seizures.” Rapid sequence MRI consisted of three plane ultrafast T2 sequences with gradient echo and diffusion weighted sequences.

The researchers compared outcomes before and after the implementation of a protocol recommending the use of rapid sequence MRI. The primary outcome was hospital length of stay. Secondary outcomes included the use of other imaging modalities (ie, head ultrasound, CT, and MRI), cost of imaging, and cost of hospitalization. They excluded neonates with clinical evidence of HIE. Continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using the chi-squared test.

In all, 95 patients (gestational age, 39 weeks; 63% male) met inclusion criteria—47 in the preintervention group and 48 in the postintervention group. The groups had similar demographics and severity of illness. Implementation of the protocol-guided rapid sequence MRI was associated with decreased use of CT (34% vs 10%) and full MRI (85% vs 62%). Use of head ultrasound (28% vs 12%), length of hospital stay, and costs were not significantly different between groups.

CHICAGO—Use of rapid sequence MRI in the evaluation of neonates with seizures and no hypoxic-ischemic encephalopathy (HIE) is associated with reduced number of CT and MRI scans and similar length of hospital stay and cost, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. “The potential reduction in radiation and sedation exposure associated with CTs and regular MRIs makes rapid sequence MRI an attractive imaging modality in this population,” said Theresa M. Czech, MD, and Andrea C. Pardo, MD, attending physicians at Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. Czech is an Instructor in Pediatrics, and Dr. Pardo is an Assistant Professor of Pediatrics, both at Northwestern University Feinberg School of Medicine in Chicago.

Neurologists routinely use brain imaging to identify the etiologies of neonatal seizures. Rapid sequence MRI “can reduce the risk of radiation associated with CT or the need for procedural sedation associated with regular MRIs,” said Drs. Czech and Pardo. “Our goal was to determine whether the implementation of a protocol recommending the use of rapid sequence MRI was associated with increased efficiency in the evaluation of neonates with seizures.” Rapid sequence MRI consisted of three plane ultrafast T2 sequences with gradient echo and diffusion weighted sequences.

The researchers compared outcomes before and after the implementation of a protocol recommending the use of rapid sequence MRI. The primary outcome was hospital length of stay. Secondary outcomes included the use of other imaging modalities (ie, head ultrasound, CT, and MRI), cost of imaging, and cost of hospitalization. They excluded neonates with clinical evidence of HIE. Continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using the chi-squared test.

In all, 95 patients (gestational age, 39 weeks; 63% male) met inclusion criteria—47 in the preintervention group and 48 in the postintervention group. The groups had similar demographics and severity of illness. Implementation of the protocol-guided rapid sequence MRI was associated with decreased use of CT (34% vs 10%) and full MRI (85% vs 62%). Use of head ultrasound (28% vs 12%), length of hospital stay, and costs were not significantly different between groups.

CHICAGO—Use of rapid sequence MRI in the evaluation of neonates with seizures and no hypoxic-ischemic encephalopathy (HIE) is associated with reduced number of CT and MRI scans and similar length of hospital stay and cost, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. “The potential reduction in radiation and sedation exposure associated with CTs and regular MRIs makes rapid sequence MRI an attractive imaging modality in this population,” said Theresa M. Czech, MD, and Andrea C. Pardo, MD, attending physicians at Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. Czech is an Instructor in Pediatrics, and Dr. Pardo is an Assistant Professor of Pediatrics, both at Northwestern University Feinberg School of Medicine in Chicago.

Neurologists routinely use brain imaging to identify the etiologies of neonatal seizures. Rapid sequence MRI “can reduce the risk of radiation associated with CT or the need for procedural sedation associated with regular MRIs,” said Drs. Czech and Pardo. “Our goal was to determine whether the implementation of a protocol recommending the use of rapid sequence MRI was associated with increased efficiency in the evaluation of neonates with seizures.” Rapid sequence MRI consisted of three plane ultrafast T2 sequences with gradient echo and diffusion weighted sequences.

The researchers compared outcomes before and after the implementation of a protocol recommending the use of rapid sequence MRI. The primary outcome was hospital length of stay. Secondary outcomes included the use of other imaging modalities (ie, head ultrasound, CT, and MRI), cost of imaging, and cost of hospitalization. They excluded neonates with clinical evidence of HIE. Continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using the chi-squared test.

In all, 95 patients (gestational age, 39 weeks; 63% male) met inclusion criteria—47 in the preintervention group and 48 in the postintervention group. The groups had similar demographics and severity of illness. Implementation of the protocol-guided rapid sequence MRI was associated with decreased use of CT (34% vs 10%) and full MRI (85% vs 62%). Use of head ultrasound (28% vs 12%), length of hospital stay, and costs were not significantly different between groups.