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FDA approves midazolam nasal spray for seizure clusters
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.
Insomnia symptoms correlate with seizure frequency
PHILADELPHIA – . Insomnia symptoms are not associated with epilepsy type, number of antiepileptic drugs (AEDs), or AED standardized dose, however.
“Given the potential benefits of sleep therapies on epilepsy outcomes, routine screening of insomnia symptoms is warranted,” said lead study author Thapanee Somboon, MD, a researcher at the sleep disorders center at Cleveland Clinic Neurological Institute in Ohio and at Prasat Neurological Institute in Bangkok.
Insomnia is common and associated with depression in patients with epilepsy, but prior studies that looked at the relationship between insomnia and epilepsy-related characteristics yielded limited and conflicting results, according to Dr. Somboon.
To evaluate potential associations between insomnia and epilepsy, Dr. Somboon and colleagues conducted a prospective analysis of data from 270 patients with epilepsy who presented to the Cleveland Clinic Epilepsy Center for an initial evaluation between January and August 2018. The patients completed the Insomnia Severity Index (ISI). An ISI score of 8 or greater indicated clinical insomnia symptoms, and an ISI score of 15 or greater indicated moderate or severe insomnia symptoms.
The researchers used Spearman’s correlation and the Kruskal-Wallis test to evaluate associations among insomnia symptoms and AED standardized dose, monthly seizure frequency, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Questionnaire (GAD-7), and Quality of Life in Epilepsy-10 (QOLIE10).
Among the 270 patients, the average age was 43.5 years, 58% were female, 74% had focal epilepsy, and 26% had one or more seizures per month. The population’s median ISI score was 7. Nearly half had an ISI score of 8 or greater, and 23% had an ISI score of 15 or greater.
“A positive correlation was found between ISI and PHQ-9 (r = 0.64, P less than .001), GAD-7 (r = 0.68, P less than .001), QOLIE (r = 0.55, P less than .001), and monthly seizure frequency (r = 0.31, P less than .001),” the researchers reported. Insomnia symptoms had a significantly stronger correlation with PHQ-9 and GAD-7 than with seizure frequency.
Dr. Somboon had no disclosures. A coinvestigator has received research support from Jazz Pharmaceuticals.
SOURCE: Somboon T et al. AAN 2019, Abstract P3.6-026.
PHILADELPHIA – . Insomnia symptoms are not associated with epilepsy type, number of antiepileptic drugs (AEDs), or AED standardized dose, however.
“Given the potential benefits of sleep therapies on epilepsy outcomes, routine screening of insomnia symptoms is warranted,” said lead study author Thapanee Somboon, MD, a researcher at the sleep disorders center at Cleveland Clinic Neurological Institute in Ohio and at Prasat Neurological Institute in Bangkok.
Insomnia is common and associated with depression in patients with epilepsy, but prior studies that looked at the relationship between insomnia and epilepsy-related characteristics yielded limited and conflicting results, according to Dr. Somboon.
To evaluate potential associations between insomnia and epilepsy, Dr. Somboon and colleagues conducted a prospective analysis of data from 270 patients with epilepsy who presented to the Cleveland Clinic Epilepsy Center for an initial evaluation between January and August 2018. The patients completed the Insomnia Severity Index (ISI). An ISI score of 8 or greater indicated clinical insomnia symptoms, and an ISI score of 15 or greater indicated moderate or severe insomnia symptoms.
The researchers used Spearman’s correlation and the Kruskal-Wallis test to evaluate associations among insomnia symptoms and AED standardized dose, monthly seizure frequency, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Questionnaire (GAD-7), and Quality of Life in Epilepsy-10 (QOLIE10).
Among the 270 patients, the average age was 43.5 years, 58% were female, 74% had focal epilepsy, and 26% had one or more seizures per month. The population’s median ISI score was 7. Nearly half had an ISI score of 8 or greater, and 23% had an ISI score of 15 or greater.
“A positive correlation was found between ISI and PHQ-9 (r = 0.64, P less than .001), GAD-7 (r = 0.68, P less than .001), QOLIE (r = 0.55, P less than .001), and monthly seizure frequency (r = 0.31, P less than .001),” the researchers reported. Insomnia symptoms had a significantly stronger correlation with PHQ-9 and GAD-7 than with seizure frequency.
Dr. Somboon had no disclosures. A coinvestigator has received research support from Jazz Pharmaceuticals.
SOURCE: Somboon T et al. AAN 2019, Abstract P3.6-026.
PHILADELPHIA – . Insomnia symptoms are not associated with epilepsy type, number of antiepileptic drugs (AEDs), or AED standardized dose, however.
“Given the potential benefits of sleep therapies on epilepsy outcomes, routine screening of insomnia symptoms is warranted,” said lead study author Thapanee Somboon, MD, a researcher at the sleep disorders center at Cleveland Clinic Neurological Institute in Ohio and at Prasat Neurological Institute in Bangkok.
Insomnia is common and associated with depression in patients with epilepsy, but prior studies that looked at the relationship between insomnia and epilepsy-related characteristics yielded limited and conflicting results, according to Dr. Somboon.
To evaluate potential associations between insomnia and epilepsy, Dr. Somboon and colleagues conducted a prospective analysis of data from 270 patients with epilepsy who presented to the Cleveland Clinic Epilepsy Center for an initial evaluation between January and August 2018. The patients completed the Insomnia Severity Index (ISI). An ISI score of 8 or greater indicated clinical insomnia symptoms, and an ISI score of 15 or greater indicated moderate or severe insomnia symptoms.
The researchers used Spearman’s correlation and the Kruskal-Wallis test to evaluate associations among insomnia symptoms and AED standardized dose, monthly seizure frequency, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Questionnaire (GAD-7), and Quality of Life in Epilepsy-10 (QOLIE10).
Among the 270 patients, the average age was 43.5 years, 58% were female, 74% had focal epilepsy, and 26% had one or more seizures per month. The population’s median ISI score was 7. Nearly half had an ISI score of 8 or greater, and 23% had an ISI score of 15 or greater.
“A positive correlation was found between ISI and PHQ-9 (r = 0.64, P less than .001), GAD-7 (r = 0.68, P less than .001), QOLIE (r = 0.55, P less than .001), and monthly seizure frequency (r = 0.31, P less than .001),” the researchers reported. Insomnia symptoms had a significantly stronger correlation with PHQ-9 and GAD-7 than with seizure frequency.
Dr. Somboon had no disclosures. A coinvestigator has received research support from Jazz Pharmaceuticals.
SOURCE: Somboon T et al. AAN 2019, Abstract P3.6-026.
REPORTING FROM AAN 2019
More than one in six patients with status epilepticus are readmitted after hospital discharge
PHILADELPHIA – according to research presented at the annual meeting of the American Academy of Neurology. It is possible to identify patients at high risk of readmission, which could allow neurologists to reduce their clinical and economic burden, said the investigators.
Status epilepticus is a major neurologic emergency. Patients often have significant disability and may represent a burden on their families and on the health care system. To identify independent predictors of 30-day hospital readmission among patients discharged after generalized convulsive status epilepticus, Mohamad Rahwan, MD, a neurologist at the Medical University of South Carolina, Charleston, and colleagues examined data from the 2014 Nationwide Readmission Database.
The investigators included adults with a primary discharge diagnosis of generalized convulsive status epilepticus, identified by the ICD-9-CM code 345.3, in their study. Patients who died during hospitalization, had missing information on the length of stay, or were discharged in December 2014 were excluded from analysis. Dr. Rahwan and colleagues calculated the overall 30-day readmission rate for the sample and compared prespecified groups by their 30-day readmission status. They performed multiple logistic regression analysis to identify independent predictors of 30-day readmission, adjusting for potential confounders.
In all, 14,562 adults were discharged with a diagnosis of generalized convulsive status epilepticus. Of this population, 2,520 patients (17.3%) were readmitted within 30 days. Multivariate logistic regression analysis indicated that patients discharged against medical advice (odds ratio, 1.45), those discharged to short-term hospital (OR, 1.39), those with comorbid conditions (OR for Charlson Comorbidity Index of 1, 1.12; OR for Charlson Comorbidity Index of 2 or greater, 1.32), and those with a length of stay exceeding 6 days (OR, 1.42) had a greater risk of 30-day readmission. The researchers observed an inverse association for patients aged 45 years or older and for those in high-income households. “Greater attention to high-risk subgroups may identify opportunities to ameliorate the clinical and economic burden of early readmissions after generalized convulsive status epilepticus,” said the researchers.
The researchers had no disclosures.
SOURCE: Rahwan M et al. AAN 2019, Abstract S36.006.
PHILADELPHIA – according to research presented at the annual meeting of the American Academy of Neurology. It is possible to identify patients at high risk of readmission, which could allow neurologists to reduce their clinical and economic burden, said the investigators.
Status epilepticus is a major neurologic emergency. Patients often have significant disability and may represent a burden on their families and on the health care system. To identify independent predictors of 30-day hospital readmission among patients discharged after generalized convulsive status epilepticus, Mohamad Rahwan, MD, a neurologist at the Medical University of South Carolina, Charleston, and colleagues examined data from the 2014 Nationwide Readmission Database.
The investigators included adults with a primary discharge diagnosis of generalized convulsive status epilepticus, identified by the ICD-9-CM code 345.3, in their study. Patients who died during hospitalization, had missing information on the length of stay, or were discharged in December 2014 were excluded from analysis. Dr. Rahwan and colleagues calculated the overall 30-day readmission rate for the sample and compared prespecified groups by their 30-day readmission status. They performed multiple logistic regression analysis to identify independent predictors of 30-day readmission, adjusting for potential confounders.
In all, 14,562 adults were discharged with a diagnosis of generalized convulsive status epilepticus. Of this population, 2,520 patients (17.3%) were readmitted within 30 days. Multivariate logistic regression analysis indicated that patients discharged against medical advice (odds ratio, 1.45), those discharged to short-term hospital (OR, 1.39), those with comorbid conditions (OR for Charlson Comorbidity Index of 1, 1.12; OR for Charlson Comorbidity Index of 2 or greater, 1.32), and those with a length of stay exceeding 6 days (OR, 1.42) had a greater risk of 30-day readmission. The researchers observed an inverse association for patients aged 45 years or older and for those in high-income households. “Greater attention to high-risk subgroups may identify opportunities to ameliorate the clinical and economic burden of early readmissions after generalized convulsive status epilepticus,” said the researchers.
The researchers had no disclosures.
SOURCE: Rahwan M et al. AAN 2019, Abstract S36.006.
PHILADELPHIA – according to research presented at the annual meeting of the American Academy of Neurology. It is possible to identify patients at high risk of readmission, which could allow neurologists to reduce their clinical and economic burden, said the investigators.
Status epilepticus is a major neurologic emergency. Patients often have significant disability and may represent a burden on their families and on the health care system. To identify independent predictors of 30-day hospital readmission among patients discharged after generalized convulsive status epilepticus, Mohamad Rahwan, MD, a neurologist at the Medical University of South Carolina, Charleston, and colleagues examined data from the 2014 Nationwide Readmission Database.
The investigators included adults with a primary discharge diagnosis of generalized convulsive status epilepticus, identified by the ICD-9-CM code 345.3, in their study. Patients who died during hospitalization, had missing information on the length of stay, or were discharged in December 2014 were excluded from analysis. Dr. Rahwan and colleagues calculated the overall 30-day readmission rate for the sample and compared prespecified groups by their 30-day readmission status. They performed multiple logistic regression analysis to identify independent predictors of 30-day readmission, adjusting for potential confounders.
In all, 14,562 adults were discharged with a diagnosis of generalized convulsive status epilepticus. Of this population, 2,520 patients (17.3%) were readmitted within 30 days. Multivariate logistic regression analysis indicated that patients discharged against medical advice (odds ratio, 1.45), those discharged to short-term hospital (OR, 1.39), those with comorbid conditions (OR for Charlson Comorbidity Index of 1, 1.12; OR for Charlson Comorbidity Index of 2 or greater, 1.32), and those with a length of stay exceeding 6 days (OR, 1.42) had a greater risk of 30-day readmission. The researchers observed an inverse association for patients aged 45 years or older and for those in high-income households. “Greater attention to high-risk subgroups may identify opportunities to ameliorate the clinical and economic burden of early readmissions after generalized convulsive status epilepticus,” said the researchers.
The researchers had no disclosures.
SOURCE: Rahwan M et al. AAN 2019, Abstract S36.006.
REPORTING FROM AAN 2019
Changes in brain networks may predict MS worsening
PHILADELPHIA – (MS), according to a study described at the annual meeting of the American Academy of Neurology.
Neurologists do not have reliable biomarkers to predict disease evolution in the medium or long term for patients with MS. The ability to predict disease evolution accurately could aid in the choice of treatment.
Maria Assunta Rocca, MD, head of the Neuroimaging of CNS White Matter Unit, Department of Neurology, Institute of Experimental Neurology, Scientific Institute Ospedale, San Raffaele, Milan, Italy, and colleagues sought to evaluate structural and functional network MRI measures as predictors of clinical deterioration over 6.5 years. They obtained conventional, 3D, T1-weighted, diffusion-weighted MRI, and resting-state functional MRI images at baseline from 233 patients with MS and 77 healthy controls. Patients underwent a neurologic examination at baseline and after a median follow-up period of 6.5 years. At follow-up, the researchers classified patients as clinically stable or worsened, according to their change in Expanded Disability Status Scale (EDSS) score. They also evaluated conversion to secondary progressive MS among patients with relapsing remitting MS at baseline.
To identify the main large-scale resting state functional connectivity networks, Dr. Rocca and colleagues applied spatial independent component analysis to resting state functional MRI data. They applied the same technique to gray matter probability maps and fractional anisotropy maps to identify the corresponding structural gray matter and white matter networks.
At follow-up, 105 patients with MS (45%) had significant EDSS worsening. Of 157 patients with relapsing remitting MS, 26 (16%) converted to secondary progressive MS. The multivariable model, after adjustment for follow-up duration, identified baseline EDSS score (odds ratio, 1.59), normalized gray matter volume (OR, 0.99), and abnormally high baseline resting state functional connectivity of the left precentral gyrus in the sensorimotor network (OR, 1.67) as predictors of EDSS worsening. These variables remained significant after the researchers adjusted for treatment effect. Independent variables associated with conversion to secondary progressive MS included baseline EDSS score (OR, 2.8) and atrophy of gray matter networks associated with sensory (OR, 0.5) and motor (OR, 0.4) functions.
Dr. Rocca received personal compensation from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche. Coauthors reported research support from Biogen, Merck Serono, Novartis, Teva, and Roche..
SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.
PHILADELPHIA – (MS), according to a study described at the annual meeting of the American Academy of Neurology.
Neurologists do not have reliable biomarkers to predict disease evolution in the medium or long term for patients with MS. The ability to predict disease evolution accurately could aid in the choice of treatment.
Maria Assunta Rocca, MD, head of the Neuroimaging of CNS White Matter Unit, Department of Neurology, Institute of Experimental Neurology, Scientific Institute Ospedale, San Raffaele, Milan, Italy, and colleagues sought to evaluate structural and functional network MRI measures as predictors of clinical deterioration over 6.5 years. They obtained conventional, 3D, T1-weighted, diffusion-weighted MRI, and resting-state functional MRI images at baseline from 233 patients with MS and 77 healthy controls. Patients underwent a neurologic examination at baseline and after a median follow-up period of 6.5 years. At follow-up, the researchers classified patients as clinically stable or worsened, according to their change in Expanded Disability Status Scale (EDSS) score. They also evaluated conversion to secondary progressive MS among patients with relapsing remitting MS at baseline.
To identify the main large-scale resting state functional connectivity networks, Dr. Rocca and colleagues applied spatial independent component analysis to resting state functional MRI data. They applied the same technique to gray matter probability maps and fractional anisotropy maps to identify the corresponding structural gray matter and white matter networks.
At follow-up, 105 patients with MS (45%) had significant EDSS worsening. Of 157 patients with relapsing remitting MS, 26 (16%) converted to secondary progressive MS. The multivariable model, after adjustment for follow-up duration, identified baseline EDSS score (odds ratio, 1.59), normalized gray matter volume (OR, 0.99), and abnormally high baseline resting state functional connectivity of the left precentral gyrus in the sensorimotor network (OR, 1.67) as predictors of EDSS worsening. These variables remained significant after the researchers adjusted for treatment effect. Independent variables associated with conversion to secondary progressive MS included baseline EDSS score (OR, 2.8) and atrophy of gray matter networks associated with sensory (OR, 0.5) and motor (OR, 0.4) functions.
Dr. Rocca received personal compensation from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche. Coauthors reported research support from Biogen, Merck Serono, Novartis, Teva, and Roche..
SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.
PHILADELPHIA – (MS), according to a study described at the annual meeting of the American Academy of Neurology.
Neurologists do not have reliable biomarkers to predict disease evolution in the medium or long term for patients with MS. The ability to predict disease evolution accurately could aid in the choice of treatment.
Maria Assunta Rocca, MD, head of the Neuroimaging of CNS White Matter Unit, Department of Neurology, Institute of Experimental Neurology, Scientific Institute Ospedale, San Raffaele, Milan, Italy, and colleagues sought to evaluate structural and functional network MRI measures as predictors of clinical deterioration over 6.5 years. They obtained conventional, 3D, T1-weighted, diffusion-weighted MRI, and resting-state functional MRI images at baseline from 233 patients with MS and 77 healthy controls. Patients underwent a neurologic examination at baseline and after a median follow-up period of 6.5 years. At follow-up, the researchers classified patients as clinically stable or worsened, according to their change in Expanded Disability Status Scale (EDSS) score. They also evaluated conversion to secondary progressive MS among patients with relapsing remitting MS at baseline.
To identify the main large-scale resting state functional connectivity networks, Dr. Rocca and colleagues applied spatial independent component analysis to resting state functional MRI data. They applied the same technique to gray matter probability maps and fractional anisotropy maps to identify the corresponding structural gray matter and white matter networks.
At follow-up, 105 patients with MS (45%) had significant EDSS worsening. Of 157 patients with relapsing remitting MS, 26 (16%) converted to secondary progressive MS. The multivariable model, after adjustment for follow-up duration, identified baseline EDSS score (odds ratio, 1.59), normalized gray matter volume (OR, 0.99), and abnormally high baseline resting state functional connectivity of the left precentral gyrus in the sensorimotor network (OR, 1.67) as predictors of EDSS worsening. These variables remained significant after the researchers adjusted for treatment effect. Independent variables associated with conversion to secondary progressive MS included baseline EDSS score (OR, 2.8) and atrophy of gray matter networks associated with sensory (OR, 0.5) and motor (OR, 0.4) functions.
Dr. Rocca received personal compensation from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche. Coauthors reported research support from Biogen, Merck Serono, Novartis, Teva, and Roche..
SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.
REPORTING FROM AAN 2019
Key clinical point: Structural and functional network MRI measures predict long-term worsening in multiple sclerosis.
Major finding: The odds ratio of worsening for patients with abnormally high baseline resting state functional connectivity is 1.67.
Study details: A prospective imaging study of 233 patients with multiple sclerosis and 77 healthy controls.
Disclosures: Dr. Rocca received personal compensation from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche. Coauthors reported research support from Biogen, Merck Serono, Novartis, Teva, and Roche.
Source: Filippi M et al. AAN 2019, Abstract S49.004.
Patients describe significant impact of epilepsy on their lives
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
PHILADELPHIA – said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.
“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.
To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).
A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).
The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).
Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.
Eisai sponsored the study.
REPORTING FROM AAN 2019
Key clinical point: Adults with focal epilepsy report a range of high-disturbance symptoms and impacts on daily life.
Major finding: The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (reported by 74% of respondents), limited ability to work and/or go to school (61%), limitations on leisure and social activities (58%), and memory loss (47%).
Study details: Qualitative, semistructured interviews with 62 adults with focal epilepsy at different stages of illness: early, middle, and late.
Disclosures: Eisai sponsored the study.
Cannabidiol reduces seizures in Dravet syndrome
Philadelphia – according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.
“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”
Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.
The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.
Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.
The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.
The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.
“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.
GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.
SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.
Philadelphia – according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.
“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”
Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.
The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.
Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.
The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.
The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.
“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.
GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.
SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.
Philadelphia – according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.
“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”
Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.
The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.
Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.
The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.
The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.
“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.
GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.
SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.
REPORTING FROM AAN 2019
Angelman syndrome treatment safe, well-tolerated, and effective in exploratory analyses
Philadelphia – according to results of a study presented at the annual meeting of the American Academy of Neurology.
Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.
This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.
“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”
OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.
A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.
Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.
Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).
These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.
“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”
Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.
Philadelphia – according to results of a study presented at the annual meeting of the American Academy of Neurology.
Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.
This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.
“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”
OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.
A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.
Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.
Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).
These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.
“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”
Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.
Philadelphia – according to results of a study presented at the annual meeting of the American Academy of Neurology.
Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.
This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.
“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”
OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.
A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.
Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.
Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).
These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.
“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”
Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.
REPORTING FROM AAN 2019
Postvaccination febrile seizures are no more severe than other febrile seizures
according to a study in Pediatrics.
Lucy Deng, MBBS, of the University of Sydney and her colleagues investigated 1,022 index febrile seizures in children aged 6 years or less, of which 6% (n = 67) were VP-FSs and 94% (n = 955) were NVP-FSs. Both univariate and multivariate analyses showed no increased risk of severe seizure associated with VP-FSs, compared with NVP-FS. Most of the febrile seizures of either type were brief (15 minutes or less) and had a length of stay of 1 day or less; there also were no differences in 24-hour recurrence. The most common symptom was respiratory, and the rates were similar in each group (62.7% with VP-FS vs. 62.8% with NVP-FS). In keeping with a known 100% increased risk associated with measles vaccination, 84% of VP-FSs were associated with measles-containing vaccines. The majority of the remaining VP-FSs occurred after combination vaccines.
One limitation is that, because these cases were documented in sentinel tertiary pediatric hospitals, the case ascertainment may not be representative. Also, the small proportion of VP-FSs and limited cohort size means the study may not have been powered to detect true differences in prolonged seizures between the groups, Dr. Deng and her colleagues wrote.
“This study confirms that VP-FSs are clinically not any different from NVP-FSs and should be managed the same way,” the researchers concluded.
The authors reported no relevant financial disclosures, although Dr. Deng is supported by the University of Sydney Training Program scholarship, and two other study authors are supported by Australian National Health and Medical Research Council Career Development Fellowships. The study was funded by a grant from the Australian Government Department of Health and the National Health and Medical Research Council.
SOURCE: Deng L et al. Pediatrics. 2019 Apr 19. doi: 10.1542/peds.2018-2120.
according to a study in Pediatrics.
Lucy Deng, MBBS, of the University of Sydney and her colleagues investigated 1,022 index febrile seizures in children aged 6 years or less, of which 6% (n = 67) were VP-FSs and 94% (n = 955) were NVP-FSs. Both univariate and multivariate analyses showed no increased risk of severe seizure associated with VP-FSs, compared with NVP-FS. Most of the febrile seizures of either type were brief (15 minutes or less) and had a length of stay of 1 day or less; there also were no differences in 24-hour recurrence. The most common symptom was respiratory, and the rates were similar in each group (62.7% with VP-FS vs. 62.8% with NVP-FS). In keeping with a known 100% increased risk associated with measles vaccination, 84% of VP-FSs were associated with measles-containing vaccines. The majority of the remaining VP-FSs occurred after combination vaccines.
One limitation is that, because these cases were documented in sentinel tertiary pediatric hospitals, the case ascertainment may not be representative. Also, the small proportion of VP-FSs and limited cohort size means the study may not have been powered to detect true differences in prolonged seizures between the groups, Dr. Deng and her colleagues wrote.
“This study confirms that VP-FSs are clinically not any different from NVP-FSs and should be managed the same way,” the researchers concluded.
The authors reported no relevant financial disclosures, although Dr. Deng is supported by the University of Sydney Training Program scholarship, and two other study authors are supported by Australian National Health and Medical Research Council Career Development Fellowships. The study was funded by a grant from the Australian Government Department of Health and the National Health and Medical Research Council.
SOURCE: Deng L et al. Pediatrics. 2019 Apr 19. doi: 10.1542/peds.2018-2120.
according to a study in Pediatrics.
Lucy Deng, MBBS, of the University of Sydney and her colleagues investigated 1,022 index febrile seizures in children aged 6 years or less, of which 6% (n = 67) were VP-FSs and 94% (n = 955) were NVP-FSs. Both univariate and multivariate analyses showed no increased risk of severe seizure associated with VP-FSs, compared with NVP-FS. Most of the febrile seizures of either type were brief (15 minutes or less) and had a length of stay of 1 day or less; there also were no differences in 24-hour recurrence. The most common symptom was respiratory, and the rates were similar in each group (62.7% with VP-FS vs. 62.8% with NVP-FS). In keeping with a known 100% increased risk associated with measles vaccination, 84% of VP-FSs were associated with measles-containing vaccines. The majority of the remaining VP-FSs occurred after combination vaccines.
One limitation is that, because these cases were documented in sentinel tertiary pediatric hospitals, the case ascertainment may not be representative. Also, the small proportion of VP-FSs and limited cohort size means the study may not have been powered to detect true differences in prolonged seizures between the groups, Dr. Deng and her colleagues wrote.
“This study confirms that VP-FSs are clinically not any different from NVP-FSs and should be managed the same way,” the researchers concluded.
The authors reported no relevant financial disclosures, although Dr. Deng is supported by the University of Sydney Training Program scholarship, and two other study authors are supported by Australian National Health and Medical Research Council Career Development Fellowships. The study was funded by a grant from the Australian Government Department of Health and the National Health and Medical Research Council.
SOURCE: Deng L et al. Pediatrics. 2019 Apr 19. doi: 10.1542/peds.2018-2120.
FROM PEDIATRICS
FDA concerned about e-cigs/seizures in youth
the agency announced April 3.
Between 2010 and early 2019, the FDA and poison control centers received 35 reports of seizures that mentioned the use of e-cigarettes. Most reports involved youth or young adults, and the reports have increased slightly since June 2018, the announcement says.
“We want to be clear that we don’t yet know if there’s a direct relationship between the use of e-cigarettes and a risk of seizure,” said FDA Commissioner Scott Gottlieb, MD, and Principal Deputy Commissioner Amy Abernethy, MD, PhD, in a statement. “We believe these 35 cases warrant scientific investigation into whether there is in fact a connection.”
In addition, the FDA is trying to determine whether any e-cigarette product-specific factors may be associated with the risk of seizures.
Seizures have been reported after a few puffs or up to 1 day after e-cigarette use and among first-time and experienced users. A few patients had a prior history of seizures or also used other substances, such as marijuana or amphetamines.
“While 35 cases may not seem like much compared to the total number of people using e-cigarettes, we are nonetheless concerned by these reported cases. We also recognized that not all of the cases may be reported,” Dr. Gottlieb and Dr. Abernethy said.
Although seizures are known side effects of nicotine toxicity and have been reported in the context of intentional or accidental swallowing of e-cigarette liquid, the voluntary reports of seizures occurring with vaping could represent a new safety issue, the FDA said.
The agency encouraged people to report cases via an online safety reporting portal. It also provided redacted case reports that involve vaping and seizures.
the agency announced April 3.
Between 2010 and early 2019, the FDA and poison control centers received 35 reports of seizures that mentioned the use of e-cigarettes. Most reports involved youth or young adults, and the reports have increased slightly since June 2018, the announcement says.
“We want to be clear that we don’t yet know if there’s a direct relationship between the use of e-cigarettes and a risk of seizure,” said FDA Commissioner Scott Gottlieb, MD, and Principal Deputy Commissioner Amy Abernethy, MD, PhD, in a statement. “We believe these 35 cases warrant scientific investigation into whether there is in fact a connection.”
In addition, the FDA is trying to determine whether any e-cigarette product-specific factors may be associated with the risk of seizures.
Seizures have been reported after a few puffs or up to 1 day after e-cigarette use and among first-time and experienced users. A few patients had a prior history of seizures or also used other substances, such as marijuana or amphetamines.
“While 35 cases may not seem like much compared to the total number of people using e-cigarettes, we are nonetheless concerned by these reported cases. We also recognized that not all of the cases may be reported,” Dr. Gottlieb and Dr. Abernethy said.
Although seizures are known side effects of nicotine toxicity and have been reported in the context of intentional or accidental swallowing of e-cigarette liquid, the voluntary reports of seizures occurring with vaping could represent a new safety issue, the FDA said.
The agency encouraged people to report cases via an online safety reporting portal. It also provided redacted case reports that involve vaping and seizures.
the agency announced April 3.
Between 2010 and early 2019, the FDA and poison control centers received 35 reports of seizures that mentioned the use of e-cigarettes. Most reports involved youth or young adults, and the reports have increased slightly since June 2018, the announcement says.
“We want to be clear that we don’t yet know if there’s a direct relationship between the use of e-cigarettes and a risk of seizure,” said FDA Commissioner Scott Gottlieb, MD, and Principal Deputy Commissioner Amy Abernethy, MD, PhD, in a statement. “We believe these 35 cases warrant scientific investigation into whether there is in fact a connection.”
In addition, the FDA is trying to determine whether any e-cigarette product-specific factors may be associated with the risk of seizures.
Seizures have been reported after a few puffs or up to 1 day after e-cigarette use and among first-time and experienced users. A few patients had a prior history of seizures or also used other substances, such as marijuana or amphetamines.
“While 35 cases may not seem like much compared to the total number of people using e-cigarettes, we are nonetheless concerned by these reported cases. We also recognized that not all of the cases may be reported,” Dr. Gottlieb and Dr. Abernethy said.
Although seizures are known side effects of nicotine toxicity and have been reported in the context of intentional or accidental swallowing of e-cigarette liquid, the voluntary reports of seizures occurring with vaping could represent a new safety issue, the FDA said.
The agency encouraged people to report cases via an online safety reporting portal. It also provided redacted case reports that involve vaping and seizures.
Valproate, topiramate prescribed in young women despite known teratogenicity risks
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
FROM JAMA NEUROLOGY
Key clinical point: Both valproate and topiramate are prescribed relatively often in women of childbearing age despite known teratogenic risks.
Major finding: Topiramate was the second- or third-most prescribed AED in the analyses. Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy.
Study details: Retrospective cohort study including nearly 47,000 women of childbearing age enrolled in claims databases between 2009 and 2013.
Disclosures: UCB Pharma sponsored the study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
Source: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.