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Oligoclonal bands, initial seizures increase risk of post-ADEM epilepsy in children
BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.
Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.
Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.
That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.
A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).
Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.
Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.
Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).
Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.
By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.
Dr. Rossor and his coauthors had no financial disclosures.
SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.
BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.
Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.
Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.
That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.
A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).
Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.
Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.
Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).
Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.
By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.
Dr. Rossor and his coauthors had no financial disclosures.
SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.
BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.
Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.
Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.
That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.
A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).
Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.
Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.
Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).
Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.
By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.
Dr. Rossor and his coauthors had no financial disclosures.
SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.
REPORTING FROM ECTRIMS 2018
Key clinical point: .
Major finding: Oligoclonal bands in CSF increased the risk of post-ADEM epilepsy by more than 20 times.
Study details: The retrospective cohort review comprised 74 children.
Disclosures: Dr. Rossor and his coauthors had no financial disclosures.
Source: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.
Modeling favors immediate AED after unprovoked first seizure
including those who are at low risk of recurrent seizures, results of a decision analysis suggest.
Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, the model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.
The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patients with a single unprovoked seizure, according to their report in Neurology.
Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, of the department of neurology, Massachusetts General Hospital, Boston, and his coauthors in their report.
“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said in a discussion of their study results.
To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.
The goal of the simulation was to determine which treatment strategy – immediate or delayed AED – would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.
The first base case was a 30-year-old man with no other risk factors for recurrent seizure, other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.
“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.
The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.
The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation indeed favored deferred AED treatment by a small margin, the investigators said.
“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they wrote.
The study was supported by the National Institutes of Health-National Institute of Neurological Disorders and Stroke. Dr. Westover and his coauthors had no relevant disclosures to report.
SOURCE: Bao EL et al. Neurology. 2018 Sep 12. pii: 10.1212/WNL.0000000000006319.
The conclusion of this decision analysis by Bao and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to authors of an accompanying editorial.
The decision analysis is based on a reasonable though not comprehensive set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, said in the editorial.
Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.
This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, quality-adjusted life years (QALYs) can be difficult to integrate into clinical decision making.
Nonetheless, the findings are worth considering in clinical practice, authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” they wrote.
Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD , are with department of neurology, Brigham and Women’s Hospital, Boston. Their editorial appeared in Neurology . Dr. Jacobs reported being partially supported by NIH/National Institute of Neurological Disorders and Stroke and is an inventor on patents related to synthesis and use of DNA-binding small molecules targeted to transcription factor–binding sites. Dr. Lee reported that he has received prior NIH funding, has served on the scientific advisory board of Lundbeck, has done contract work for SleepMed/DigiTrace and Advance Medical.
The conclusion of this decision analysis by Bao and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to authors of an accompanying editorial.
The decision analysis is based on a reasonable though not comprehensive set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, said in the editorial.
Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.
This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, quality-adjusted life years (QALYs) can be difficult to integrate into clinical decision making.
Nonetheless, the findings are worth considering in clinical practice, authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” they wrote.
Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD , are with department of neurology, Brigham and Women’s Hospital, Boston. Their editorial appeared in Neurology . Dr. Jacobs reported being partially supported by NIH/National Institute of Neurological Disorders and Stroke and is an inventor on patents related to synthesis and use of DNA-binding small molecules targeted to transcription factor–binding sites. Dr. Lee reported that he has received prior NIH funding, has served on the scientific advisory board of Lundbeck, has done contract work for SleepMed/DigiTrace and Advance Medical.
The conclusion of this decision analysis by Bao and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to authors of an accompanying editorial.
The decision analysis is based on a reasonable though not comprehensive set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, said in the editorial.
Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.
This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, quality-adjusted life years (QALYs) can be difficult to integrate into clinical decision making.
Nonetheless, the findings are worth considering in clinical practice, authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” they wrote.
Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD , are with department of neurology, Brigham and Women’s Hospital, Boston. Their editorial appeared in Neurology . Dr. Jacobs reported being partially supported by NIH/National Institute of Neurological Disorders and Stroke and is an inventor on patents related to synthesis and use of DNA-binding small molecules targeted to transcription factor–binding sites. Dr. Lee reported that he has received prior NIH funding, has served on the scientific advisory board of Lundbeck, has done contract work for SleepMed/DigiTrace and Advance Medical.
including those who are at low risk of recurrent seizures, results of a decision analysis suggest.
Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, the model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.
The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patients with a single unprovoked seizure, according to their report in Neurology.
Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, of the department of neurology, Massachusetts General Hospital, Boston, and his coauthors in their report.
“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said in a discussion of their study results.
To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.
The goal of the simulation was to determine which treatment strategy – immediate or delayed AED – would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.
The first base case was a 30-year-old man with no other risk factors for recurrent seizure, other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.
“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.
The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.
The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation indeed favored deferred AED treatment by a small margin, the investigators said.
“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they wrote.
The study was supported by the National Institutes of Health-National Institute of Neurological Disorders and Stroke. Dr. Westover and his coauthors had no relevant disclosures to report.
SOURCE: Bao EL et al. Neurology. 2018 Sep 12. pii: 10.1212/WNL.0000000000006319.
including those who are at low risk of recurrent seizures, results of a decision analysis suggest.
Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, the model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.
The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patients with a single unprovoked seizure, according to their report in Neurology.
Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, of the department of neurology, Massachusetts General Hospital, Boston, and his coauthors in their report.
“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said in a discussion of their study results.
To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.
The goal of the simulation was to determine which treatment strategy – immediate or delayed AED – would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.
The first base case was a 30-year-old man with no other risk factors for recurrent seizure, other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.
“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.
The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.
The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation indeed favored deferred AED treatment by a small margin, the investigators said.
“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they wrote.
The study was supported by the National Institutes of Health-National Institute of Neurological Disorders and Stroke. Dr. Westover and his coauthors had no relevant disclosures to report.
SOURCE: Bao EL et al. Neurology. 2018 Sep 12. pii: 10.1212/WNL.0000000000006319.
FROM NEUROLOGY
Key clinical point: Based on quality-adjusted life years (QALYs), immediate treatment of a first unprovoked seizure may be preferable to delayed treatment over a wide range of patients, including those who are at low risk of recurrent seizures.
Major finding: In a base case of a first unprovoked seizure and no other risk factors for recurrent seizure, immediate, and deferred antiepileptic drug treatment resulted in 19.04 and 18.65 QALYs, respectively.
Study details: A simulated clinical trial using decision analysis modeling, which included three base cases representing various degrees of seizure recurrence risk.
Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke. Study authors had no relevant disclosures to report.
Source: Bao EL et al. Neurology. 2018 Sep 12. pii: 10.1212/WNL.0000000000006319.
Pediatric Status Epilepticus Takes Heavy Toll
Pediatric status epilepticus (SE) is an expensive disorder and is not uncommon in this patient population, according to a recent review of the medical literature.
- Gurcharran et al note that pediatric SE occurs in about 20per 100,000 children each year.
- The disorder carries a mortality of 3%.
- The most common risk factor for morbidity and death is symptomatic etiology, with acute presentation more common than remote.
- A single episode of status epilepticus costs more than $10,000 to manage and can reach more than $100,000 in children with refractory disease.
- The most common cause of the condition is febrile SE, which usually occurs in early childhood.
Gurcharran K, Grinspan ZM. The burden of pediatric status epilepticus: epidemiology, morbidity, and mortality. [Published online ahead of print August 29, 2018] Seizure. https://doi.org/10.1016/j.seizure.2018.08.021.
Pediatric status epilepticus (SE) is an expensive disorder and is not uncommon in this patient population, according to a recent review of the medical literature.
- Gurcharran et al note that pediatric SE occurs in about 20per 100,000 children each year.
- The disorder carries a mortality of 3%.
- The most common risk factor for morbidity and death is symptomatic etiology, with acute presentation more common than remote.
- A single episode of status epilepticus costs more than $10,000 to manage and can reach more than $100,000 in children with refractory disease.
- The most common cause of the condition is febrile SE, which usually occurs in early childhood.
Gurcharran K, Grinspan ZM. The burden of pediatric status epilepticus: epidemiology, morbidity, and mortality. [Published online ahead of print August 29, 2018] Seizure. https://doi.org/10.1016/j.seizure.2018.08.021.
Pediatric status epilepticus (SE) is an expensive disorder and is not uncommon in this patient population, according to a recent review of the medical literature.
- Gurcharran et al note that pediatric SE occurs in about 20per 100,000 children each year.
- The disorder carries a mortality of 3%.
- The most common risk factor for morbidity and death is symptomatic etiology, with acute presentation more common than remote.
- A single episode of status epilepticus costs more than $10,000 to manage and can reach more than $100,000 in children with refractory disease.
- The most common cause of the condition is febrile SE, which usually occurs in early childhood.
Gurcharran K, Grinspan ZM. The burden of pediatric status epilepticus: epidemiology, morbidity, and mortality. [Published online ahead of print August 29, 2018] Seizure. https://doi.org/10.1016/j.seizure.2018.08.021.
Are New Treatments for Pediatric Refractory Status Epilepticus Effective?
While several emerging treatments have been recommended for children with refractory status epilepticus, most of the research supporting these modalities are anecdotal in nature, according to a review published in Seizure.
- Randomized controlled trials have evaluated hypothermia and found it is no more effective than placebo for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE).
- Case series have suggested that a ketogenic diet may benefit children with RSE.
- A few case reports involving the ketogenic diet found seizures were stopped within a week in 20-90% of children.
- One double blind trial concluded that brexanolone was no more effective than placebo for weaning patients off 3rd line anesthetic agents and freedom from RSE after 24 hours.
Arya R, Rotenberg A. Dietary, immunological, surgical, and other emerging treatments for pediatric refractory status epilepticus. [Published online ahead of print Sept 14, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.002.
While several emerging treatments have been recommended for children with refractory status epilepticus, most of the research supporting these modalities are anecdotal in nature, according to a review published in Seizure.
- Randomized controlled trials have evaluated hypothermia and found it is no more effective than placebo for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE).
- Case series have suggested that a ketogenic diet may benefit children with RSE.
- A few case reports involving the ketogenic diet found seizures were stopped within a week in 20-90% of children.
- One double blind trial concluded that brexanolone was no more effective than placebo for weaning patients off 3rd line anesthetic agents and freedom from RSE after 24 hours.
Arya R, Rotenberg A. Dietary, immunological, surgical, and other emerging treatments for pediatric refractory status epilepticus. [Published online ahead of print Sept 14, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.002.
While several emerging treatments have been recommended for children with refractory status epilepticus, most of the research supporting these modalities are anecdotal in nature, according to a review published in Seizure.
- Randomized controlled trials have evaluated hypothermia and found it is no more effective than placebo for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE).
- Case series have suggested that a ketogenic diet may benefit children with RSE.
- A few case reports involving the ketogenic diet found seizures were stopped within a week in 20-90% of children.
- One double blind trial concluded that brexanolone was no more effective than placebo for weaning patients off 3rd line anesthetic agents and freedom from RSE after 24 hours.
Arya R, Rotenberg A. Dietary, immunological, surgical, and other emerging treatments for pediatric refractory status epilepticus. [Published online ahead of print Sept 14, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.002.
Cross Sensitivity of Antiepileptic Side Effects
Patients will likely develop intolerable psychiatric and behavioral side effects (IPBSE) to an antiepileptic drug if they are already sensitive to another one, according to researchers from Yale and Columbia University.
- A review of the records of over 2,000 patients found that about 20% were taking at least two antiepileptic drug and had at IPBSE to at least one of the drugs.
- Cross sensitivity was detected between zonisamide and levetiracetam.
- The odds of developing said side effects from levetiracetam or from zonisamide were significantly higher in a patient that had had a side effect to another antiepileptic drug than in patients who had no IPBSE to other antiepileptic drugs (20.5% versus 7.5%.)
- A history of depression and psychosis increase the risk of IPBSE among patients taking antiepileptic medication.
Chen B, Choi H, Hirsch LJ, et al. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. [Published online ahead of print Sept 22, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.014.
Patients will likely develop intolerable psychiatric and behavioral side effects (IPBSE) to an antiepileptic drug if they are already sensitive to another one, according to researchers from Yale and Columbia University.
- A review of the records of over 2,000 patients found that about 20% were taking at least two antiepileptic drug and had at IPBSE to at least one of the drugs.
- Cross sensitivity was detected between zonisamide and levetiracetam.
- The odds of developing said side effects from levetiracetam or from zonisamide were significantly higher in a patient that had had a side effect to another antiepileptic drug than in patients who had no IPBSE to other antiepileptic drugs (20.5% versus 7.5%.)
- A history of depression and psychosis increase the risk of IPBSE among patients taking antiepileptic medication.
Chen B, Choi H, Hirsch LJ, et al. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. [Published online ahead of print Sept 22, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.014.
Patients will likely develop intolerable psychiatric and behavioral side effects (IPBSE) to an antiepileptic drug if they are already sensitive to another one, according to researchers from Yale and Columbia University.
- A review of the records of over 2,000 patients found that about 20% were taking at least two antiepileptic drug and had at IPBSE to at least one of the drugs.
- Cross sensitivity was detected between zonisamide and levetiracetam.
- The odds of developing said side effects from levetiracetam or from zonisamide were significantly higher in a patient that had had a side effect to another antiepileptic drug than in patients who had no IPBSE to other antiepileptic drugs (20.5% versus 7.5%.)
- A history of depression and psychosis increase the risk of IPBSE among patients taking antiepileptic medication.
Chen B, Choi H, Hirsch LJ, et al. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. [Published online ahead of print Sept 22, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.014.
Disrupted Sleep, Cardiorespiratory Dysfunction Linked to SUDEP
Periictal cardiorespiratory dysfunction, sleep-disordered breathing, and endocrine dysfunction have all been linked to sudden unexpected death from epilepsy (SUDEP).
- Investigators conducted a prospective observational study on 30 patients in the Columbia University Medical Center’s adult epilepsy monitoring unit.
- Their analysis found that patients who were at high risk for SUDEP were more likely to experience cardiorespiratory dysfunction (60% vs 27%).
- Sleep-disordered breathing was found in 88% of patients with inpatient or outpatient polysomnography results that were fully scorable.
- The researchers also found endocrine dysfunction in 35% of patients, with men more likely to experience the problem.
- The analysis did not detect a significant relationship between cardiorespiratory dysfunction, sleep-disordered breathing, and neuroendocrine status.
Billakota S, Odom N, Westwood AJ, et al. Sleep-disordered breathing, neuroendocrine function, and clinical SUDEP risk in patients with epilepsy. Epilepsy Behav. 2018;87:78-82.
Periictal cardiorespiratory dysfunction, sleep-disordered breathing, and endocrine dysfunction have all been linked to sudden unexpected death from epilepsy (SUDEP).
- Investigators conducted a prospective observational study on 30 patients in the Columbia University Medical Center’s adult epilepsy monitoring unit.
- Their analysis found that patients who were at high risk for SUDEP were more likely to experience cardiorespiratory dysfunction (60% vs 27%).
- Sleep-disordered breathing was found in 88% of patients with inpatient or outpatient polysomnography results that were fully scorable.
- The researchers also found endocrine dysfunction in 35% of patients, with men more likely to experience the problem.
- The analysis did not detect a significant relationship between cardiorespiratory dysfunction, sleep-disordered breathing, and neuroendocrine status.
Billakota S, Odom N, Westwood AJ, et al. Sleep-disordered breathing, neuroendocrine function, and clinical SUDEP risk in patients with epilepsy. Epilepsy Behav. 2018;87:78-82.
Periictal cardiorespiratory dysfunction, sleep-disordered breathing, and endocrine dysfunction have all been linked to sudden unexpected death from epilepsy (SUDEP).
- Investigators conducted a prospective observational study on 30 patients in the Columbia University Medical Center’s adult epilepsy monitoring unit.
- Their analysis found that patients who were at high risk for SUDEP were more likely to experience cardiorespiratory dysfunction (60% vs 27%).
- Sleep-disordered breathing was found in 88% of patients with inpatient or outpatient polysomnography results that were fully scorable.
- The researchers also found endocrine dysfunction in 35% of patients, with men more likely to experience the problem.
- The analysis did not detect a significant relationship between cardiorespiratory dysfunction, sleep-disordered breathing, and neuroendocrine status.
Billakota S, Odom N, Westwood AJ, et al. Sleep-disordered breathing, neuroendocrine function, and clinical SUDEP risk in patients with epilepsy. Epilepsy Behav. 2018;87:78-82.
Quality of Life in Pediatric Epilepsy Dependent on Parental Coping
Health-related quality of life for children with epilepsy appears to be dependent in part on their parents’ ability to cope with the disorder, according to a recent study published in Epilepsy and Behavior.
- The analysis of 108 children and teens with epilepsy also revealed an association between parental helplessness and poorer quality of life.
- As expected, the severity of the child’s epilepsy was linked to poorer quality of life as well.
- These conclusions were based on parents’ responses to the Illness Cognition Questionnaire-Parent (ICQ-P), and the Quality of Life in Childhood Epilepsy questionnaire (QOLCE).
- ICQ-P evaluates a parent’s ability to cope with disease with the help of constructs of illness cognition.
- QOLCE helps clinicians evaluates the overall functioning of a child as perceived by parents.
McLaughlin RM, Schraegle WA, Nussbaum NL, et al. Parental coping and its role in predicting health-related quality of life in pediatric epilepsy. [Published online ahead of print August 23, 2018] Epilepsy Behav. doi: 10.1016/j.yebeh.2018.08.009
Health-related quality of life for children with epilepsy appears to be dependent in part on their parents’ ability to cope with the disorder, according to a recent study published in Epilepsy and Behavior.
- The analysis of 108 children and teens with epilepsy also revealed an association between parental helplessness and poorer quality of life.
- As expected, the severity of the child’s epilepsy was linked to poorer quality of life as well.
- These conclusions were based on parents’ responses to the Illness Cognition Questionnaire-Parent (ICQ-P), and the Quality of Life in Childhood Epilepsy questionnaire (QOLCE).
- ICQ-P evaluates a parent’s ability to cope with disease with the help of constructs of illness cognition.
- QOLCE helps clinicians evaluates the overall functioning of a child as perceived by parents.
McLaughlin RM, Schraegle WA, Nussbaum NL, et al. Parental coping and its role in predicting health-related quality of life in pediatric epilepsy. [Published online ahead of print August 23, 2018] Epilepsy Behav. doi: 10.1016/j.yebeh.2018.08.009
Health-related quality of life for children with epilepsy appears to be dependent in part on their parents’ ability to cope with the disorder, according to a recent study published in Epilepsy and Behavior.
- The analysis of 108 children and teens with epilepsy also revealed an association between parental helplessness and poorer quality of life.
- As expected, the severity of the child’s epilepsy was linked to poorer quality of life as well.
- These conclusions were based on parents’ responses to the Illness Cognition Questionnaire-Parent (ICQ-P), and the Quality of Life in Childhood Epilepsy questionnaire (QOLCE).
- ICQ-P evaluates a parent’s ability to cope with disease with the help of constructs of illness cognition.
- QOLCE helps clinicians evaluates the overall functioning of a child as perceived by parents.
McLaughlin RM, Schraegle WA, Nussbaum NL, et al. Parental coping and its role in predicting health-related quality of life in pediatric epilepsy. [Published online ahead of print August 23, 2018] Epilepsy Behav. doi: 10.1016/j.yebeh.2018.08.009
DEA moves Epidiolex to schedule V, clearing the way for marketing
Epidiolex, a cannabis-derived product approved earlier this year by the Food and Drug Administration for the treatment of childhood seizure syndromes, has been reclassified by the Drug Enforcement Administration. This paves the way for the manufacturer to begin marketing Epidiolex, which is expected to be on the market within 6 weeks.
GW Pharmaceuticals, in a Sept. 27 press release announcing the rescheduling of the company’s oral cannabidiol (CBD) solution, said that .
The final rescheduling order from the DEA is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinols. 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.
“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS [Lennox-Gastaut syndrome] 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 from the company announcing the reclassification.
During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndromes, both the FDA and GW Pharmaceuticals assessed the abuse potential for CBD as very low, since it does not contain tetrahydrocannabinol, the primary psychoactive component of cannabis.
All other marijuana products are currently classified as schedule I drugs, along with such illegal substances as heroin and cocaine.
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 endpoint of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and Dravet syndrome.
Safety evaluations assessed data from 1,756 patients, finding that the 20 deaths seen during the study period were not clearly linked to Epidiolex and not unexpected 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 CSA [Controlled Substances Act]. Accordingly, Epidiolex no longer meets the criteria for placement in schedule I of the CSA.” Schedule I drugs, by definition, do not have a currently accepted medical use.
Schedule V drugs, according to the DEA’s website, are currently defined as “drugs with lower potential for abuse than schedule IV and consist of preparations containing limited quantities of certain narcotics.” Other schedule V drugs include cough medicine with less than 200 mg of codeine/100 mL, antidiarrheal medications, pregabalin (Lyrica), and the antiepileptics brivaracetam (Briviact) and lacosamide (Vimpat). “Schedule V drugs represents the least potential for abuse,” according to the website.
Epidiolex is indicated for adjunctive treatment of seizures in patients with LGS or Dravet syndrome aged 2 years and older. Initial dosing recommendations are to titrate to a dose of 10 mg/kg/day, with dose adjustments permissible up to 20 mg/kg/day depending on clinical response and tolerability. The manufacturer has also submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of another seizure disorder, tuberous sclerosis complex.
Epidiolex, a cannabis-derived product approved earlier this year by the Food and Drug Administration for the treatment of childhood seizure syndromes, has been reclassified by the Drug Enforcement Administration. This paves the way for the manufacturer to begin marketing Epidiolex, which is expected to be on the market within 6 weeks.
GW Pharmaceuticals, in a Sept. 27 press release announcing the rescheduling of the company’s oral cannabidiol (CBD) solution, said that .
The final rescheduling order from the DEA is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinols. 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.
“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS [Lennox-Gastaut syndrome] 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 from the company announcing the reclassification.
During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndromes, both the FDA and GW Pharmaceuticals assessed the abuse potential for CBD as very low, since it does not contain tetrahydrocannabinol, the primary psychoactive component of cannabis.
All other marijuana products are currently classified as schedule I drugs, along with such illegal substances as heroin and cocaine.
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 endpoint of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and Dravet syndrome.
Safety evaluations assessed data from 1,756 patients, finding that the 20 deaths seen during the study period were not clearly linked to Epidiolex and not unexpected 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 CSA [Controlled Substances Act]. Accordingly, Epidiolex no longer meets the criteria for placement in schedule I of the CSA.” Schedule I drugs, by definition, do not have a currently accepted medical use.
Schedule V drugs, according to the DEA’s website, are currently defined as “drugs with lower potential for abuse than schedule IV and consist of preparations containing limited quantities of certain narcotics.” Other schedule V drugs include cough medicine with less than 200 mg of codeine/100 mL, antidiarrheal medications, pregabalin (Lyrica), and the antiepileptics brivaracetam (Briviact) and lacosamide (Vimpat). “Schedule V drugs represents the least potential for abuse,” according to the website.
Epidiolex is indicated for adjunctive treatment of seizures in patients with LGS or Dravet syndrome aged 2 years and older. Initial dosing recommendations are to titrate to a dose of 10 mg/kg/day, with dose adjustments permissible up to 20 mg/kg/day depending on clinical response and tolerability. The manufacturer has also submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of another seizure disorder, tuberous sclerosis complex.
Epidiolex, a cannabis-derived product approved earlier this year by the Food and Drug Administration for the treatment of childhood seizure syndromes, has been reclassified by the Drug Enforcement Administration. This paves the way for the manufacturer to begin marketing Epidiolex, which is expected to be on the market within 6 weeks.
GW Pharmaceuticals, in a Sept. 27 press release announcing the rescheduling of the company’s oral cannabidiol (CBD) solution, said that .
The final rescheduling order from the DEA is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinols. 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.
“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS [Lennox-Gastaut syndrome] 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 from the company announcing the reclassification.
During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndromes, both the FDA and GW Pharmaceuticals assessed the abuse potential for CBD as very low, since it does not contain tetrahydrocannabinol, the primary psychoactive component of cannabis.
All other marijuana products are currently classified as schedule I drugs, along with such illegal substances as heroin and cocaine.
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 endpoint of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and Dravet syndrome.
Safety evaluations assessed data from 1,756 patients, finding that the 20 deaths seen during the study period were not clearly linked to Epidiolex and not unexpected 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 CSA [Controlled Substances Act]. Accordingly, Epidiolex no longer meets the criteria for placement in schedule I of the CSA.” Schedule I drugs, by definition, do not have a currently accepted medical use.
Schedule V drugs, according to the DEA’s website, are currently defined as “drugs with lower potential for abuse than schedule IV and consist of preparations containing limited quantities of certain narcotics.” Other schedule V drugs include cough medicine with less than 200 mg of codeine/100 mL, antidiarrheal medications, pregabalin (Lyrica), and the antiepileptics brivaracetam (Briviact) and lacosamide (Vimpat). “Schedule V drugs represents the least potential for abuse,” according to the website.
Epidiolex is indicated for adjunctive treatment of seizures in patients with LGS or Dravet syndrome aged 2 years and older. Initial dosing recommendations are to titrate to a dose of 10 mg/kg/day, with dose adjustments permissible up to 20 mg/kg/day depending on clinical response and tolerability. The manufacturer has also submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of another seizure disorder, tuberous sclerosis complex.
Multiday Seizure Cycles May Be Common
Tracking seizure cycles could facilitate personalized medicine and improve seizure reduction.
Multiday epileptic seizure cycles may occur in many individuals with epilepsy, according to a retrospective cohort study published online ahead of print September 12 in Lancet Neurology.
About 80% of patients in the study showed circadian modulation of their seizure rates, and more than 20% had strong circaseptan (ie, seven-day) rhythms, said Mark J. Cook, MD, a neurologist at St. Vincent’s Hospital in Melbourne, and colleagues. 
The high prevalence of multiday seizure cycles could present an opportunity to improve treatment through the development of patient-specific chronotherapy (ie, the administration of medication when seizures are most likely). “Even without fully understanding the mechanisms of seizure cycles, temporal patterns can be incorporated into patient management plans,” said Dr. Cook.
The investigators based their study on two seizure datasets. One was a US cohort of 1,118 patients who reported at least 100 seizures through the SeizureTracker website or mobile app. The other was an Australian cohort of 12 patients with focal epilepsy who had at least 30 seizures recorded by an implanted electrocorticography device during follow-up that ranged between six months and three years.
In the US cohort, 86% of participants had at least one significant cycle in their seizure times, and 64% had more than one cycle. Most of the cycles (80%) were circadian, while 21% of people had significant circaseptan cycles in one analysis using the Hodges-Ajne test, a statistical method used to test for circular uniformity. “Many patients also showed some evidence of cycles lasting up to a month,” said the authors.
A confirmatory analysis using Monte Carlo simulation found that 7% of people, or 77 individuals, had significant circaseptan cycles. “The probability that 77 patients would randomly share a specific cycle is infinitesimal,” said the authors.
In the Australian study, 11 of 12 patients had strong rhythms at 24 hours, one had a significant cycle of exactly one week, and two others had cycles of approximately one week.
“Some people had stronger rhythms at time scales longer than 24 hours, which suggests that circadian regulation was not necessarily the strongest modulating factor of epileptic activity,” said the investigators. The cause of longer seizure cycles remains unclear, though peak seizure times might be linked to varying stress levels, seasonal changes in sleep quality, or biologic cycles such as menstruation.
—Andrew D. Bowser
Suggested Reading
Karoly PJ, Goldenholz DM, Freestone DR, et al. Circadian and circaseptan rhythms in human epilepsy: a retrospective cohort study. Lancet Neurol. 2018 Sep 12 [Epub ahead of print].
Tracking seizure cycles could facilitate personalized medicine and improve seizure reduction.
Tracking seizure cycles could facilitate personalized medicine and improve seizure reduction.
Multiday epileptic seizure cycles may occur in many individuals with epilepsy, according to a retrospective cohort study published online ahead of print September 12 in Lancet Neurology.
About 80% of patients in the study showed circadian modulation of their seizure rates, and more than 20% had strong circaseptan (ie, seven-day) rhythms, said Mark J. Cook, MD, a neurologist at St. Vincent’s Hospital in Melbourne, and colleagues.
The high prevalence of multiday seizure cycles could present an opportunity to improve treatment through the development of patient-specific chronotherapy (ie, the administration of medication when seizures are most likely). “Even without fully understanding the mechanisms of seizure cycles, temporal patterns can be incorporated into patient management plans,” said Dr. Cook.
The investigators based their study on two seizure datasets. One was a US cohort of 1,118 patients who reported at least 100 seizures through the SeizureTracker website or mobile app. The other was an Australian cohort of 12 patients with focal epilepsy who had at least 30 seizures recorded by an implanted electrocorticography device during follow-up that ranged between six months and three years.
In the US cohort, 86% of participants had at least one significant cycle in their seizure times, and 64% had more than one cycle. Most of the cycles (80%) were circadian, while 21% of people had significant circaseptan cycles in one analysis using the Hodges-Ajne test, a statistical method used to test for circular uniformity. “Many patients also showed some evidence of cycles lasting up to a month,” said the authors.
A confirmatory analysis using Monte Carlo simulation found that 7% of people, or 77 individuals, had significant circaseptan cycles. “The probability that 77 patients would randomly share a specific cycle is infinitesimal,” said the authors.
In the Australian study, 11 of 12 patients had strong rhythms at 24 hours, one had a significant cycle of exactly one week, and two others had cycles of approximately one week.
“Some people had stronger rhythms at time scales longer than 24 hours, which suggests that circadian regulation was not necessarily the strongest modulating factor of epileptic activity,” said the investigators. The cause of longer seizure cycles remains unclear, though peak seizure times might be linked to varying stress levels, seasonal changes in sleep quality, or biologic cycles such as menstruation.
—Andrew D. Bowser
Suggested Reading
Karoly PJ, Goldenholz DM, Freestone DR, et al. Circadian and circaseptan rhythms in human epilepsy: a retrospective cohort study. Lancet Neurol. 2018 Sep 12 [Epub ahead of print].
Multiday epileptic seizure cycles may occur in many individuals with epilepsy, according to a retrospective cohort study published online ahead of print September 12 in Lancet Neurology.
About 80% of patients in the study showed circadian modulation of their seizure rates, and more than 20% had strong circaseptan (ie, seven-day) rhythms, said Mark J. Cook, MD, a neurologist at St. Vincent’s Hospital in Melbourne, and colleagues.
The high prevalence of multiday seizure cycles could present an opportunity to improve treatment through the development of patient-specific chronotherapy (ie, the administration of medication when seizures are most likely). “Even without fully understanding the mechanisms of seizure cycles, temporal patterns can be incorporated into patient management plans,” said Dr. Cook.
The investigators based their study on two seizure datasets. One was a US cohort of 1,118 patients who reported at least 100 seizures through the SeizureTracker website or mobile app. The other was an Australian cohort of 12 patients with focal epilepsy who had at least 30 seizures recorded by an implanted electrocorticography device during follow-up that ranged between six months and three years.
In the US cohort, 86% of participants had at least one significant cycle in their seizure times, and 64% had more than one cycle. Most of the cycles (80%) were circadian, while 21% of people had significant circaseptan cycles in one analysis using the Hodges-Ajne test, a statistical method used to test for circular uniformity. “Many patients also showed some evidence of cycles lasting up to a month,” said the authors.
A confirmatory analysis using Monte Carlo simulation found that 7% of people, or 77 individuals, had significant circaseptan cycles. “The probability that 77 patients would randomly share a specific cycle is infinitesimal,” said the authors.
In the Australian study, 11 of 12 patients had strong rhythms at 24 hours, one had a significant cycle of exactly one week, and two others had cycles of approximately one week.
“Some people had stronger rhythms at time scales longer than 24 hours, which suggests that circadian regulation was not necessarily the strongest modulating factor of epileptic activity,” said the investigators. The cause of longer seizure cycles remains unclear, though peak seizure times might be linked to varying stress levels, seasonal changes in sleep quality, or biologic cycles such as menstruation.
—Andrew D. Bowser
Suggested Reading
Karoly PJ, Goldenholz DM, Freestone DR, et al. Circadian and circaseptan rhythms in human epilepsy: a retrospective cohort study. Lancet Neurol. 2018 Sep 12 [Epub ahead of print].
Long-Term Data Suggest Benefits of Adjunctive CBD in Treatment-Resistant Epilepsies
The drug promotes sustained reductions in seizure frequency and contributes to seizure freedom for some patients.
Pooled data from an expanded-access program provide further evidence that adjunctive cannabidiol (CBD) provides meaningful reductions in seizure frequency in patients with treatment-resistant epilepsies. The data were published in the August issue of Epilepsia.
Studies have recently indicated that adjunctive CBD effectively reduces seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. An expanded-access program was created in January 2014 to offer CBD to patients with treatment-resistant epilepsies. Data on safety, tolerability, and efficacy during the first year of the study have been reported. Jerzy P. Szaflarski, MD, PhD, Professor of Neurology at the University of Alabama at Birmingham, and colleagues examined results for safety outcomes at 144 weeks and efficacy outcomes at 96 weeks. 
An Expanded-Access Program
All participants in the program had treatment-resistant epilepsy and were receiving stable doses of antiepileptic drugs (AEDs) for at least four weeks before enrollment. During a four-week baseline period, parents and caregivers kept diaries of all countable seizure types. Participants subsequently received a plant-based oral pharmaceutical formulation of CBD (100 mg/mL). Treatment was initiated at a dose of 2–10 mg/kg/day and was titrated to a maximum dose of 25–50 mg/kg/day.
Patients were examined every two to four weeks until the 16th week, and every two to 12 weeks after that point. The efficacy outcomes included the percentage change from baseline in median monthly convulsive seizure frequency and total seizure frequency, and the percentages of patients with at least 50%, at least 75%, and 100% reductions in seizures, compared with baseline. Investigators documented adverse events at each visit.
CBD Was Well Tolerated
The safety analysis included 607 patients, and the efficacy analysis included 580 patients. Among patients included in the safety analysis, 24% withdrew from the study. The most common reasons for withdrawal were lack of efficacy (15%) and adverse events (5%). Participants’ mean age was 13, and 52% of patients were male. The median number of concomitant AEDs was three, the median dose of CBD was 25 mg/kg/day, and the median treatment duration was 48 weeks.
At 12 weeks, adjunctive CBD was associated with a 51% reduction in median monthly convulsive seizures and a 48% reduction in total seizures. Reductions in these seizure types were similar through 96 weeks. At 12 weeks, 52% of patients had a reduction in convulsive seizures of at least 50%, 31% had a reduction of at least 75%, and 11% had a 100% reduction. These response rates were similar through 96 weeks of treatment.
CBD was generally well tolerated. The most common adverse events were diarrhea (29%) and somnolence (22%). About 10% of patients had abnormal liver adverse events, and 75% of them were taking valproate. Among patients taking concomitant clobazam, 38% had somnolence, compared with 14% of patients not taking concomitant clobazam.
The expanded-access program is not placebo-controlled, and neither patients nor investigators are blinded. Furthermore, reporting methods varied between study sites. Despite these limitations, the data indicate that adjunctive CBD significantly reduces seizure frequency, according to the authors.
The data support the results of double-blind, placebo-controlled trials that found that add-on CBD reduces seizure frequency, compared with placebo. The FDA in June approved Epidiolex, the formulation of CBD used in the expanded-access program, for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome.
—Erik Greb
Suggested Reading
Szaflarski JP, Bebin EM, Comi AM, et al. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia. 2018;59(8):1540-1548.
The drug promotes sustained reductions in seizure frequency and contributes to seizure freedom for some patients.
The drug promotes sustained reductions in seizure frequency and contributes to seizure freedom for some patients.
Pooled data from an expanded-access program provide further evidence that adjunctive cannabidiol (CBD) provides meaningful reductions in seizure frequency in patients with treatment-resistant epilepsies. The data were published in the August issue of Epilepsia.
Studies have recently indicated that adjunctive CBD effectively reduces seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. An expanded-access program was created in January 2014 to offer CBD to patients with treatment-resistant epilepsies. Data on safety, tolerability, and efficacy during the first year of the study have been reported. Jerzy P. Szaflarski, MD, PhD, Professor of Neurology at the University of Alabama at Birmingham, and colleagues examined results for safety outcomes at 144 weeks and efficacy outcomes at 96 weeks.
An Expanded-Access Program
All participants in the program had treatment-resistant epilepsy and were receiving stable doses of antiepileptic drugs (AEDs) for at least four weeks before enrollment. During a four-week baseline period, parents and caregivers kept diaries of all countable seizure types. Participants subsequently received a plant-based oral pharmaceutical formulation of CBD (100 mg/mL). Treatment was initiated at a dose of 2–10 mg/kg/day and was titrated to a maximum dose of 25–50 mg/kg/day.
Patients were examined every two to four weeks until the 16th week, and every two to 12 weeks after that point. The efficacy outcomes included the percentage change from baseline in median monthly convulsive seizure frequency and total seizure frequency, and the percentages of patients with at least 50%, at least 75%, and 100% reductions in seizures, compared with baseline. Investigators documented adverse events at each visit.
CBD Was Well Tolerated
The safety analysis included 607 patients, and the efficacy analysis included 580 patients. Among patients included in the safety analysis, 24% withdrew from the study. The most common reasons for withdrawal were lack of efficacy (15%) and adverse events (5%). Participants’ mean age was 13, and 52% of patients were male. The median number of concomitant AEDs was three, the median dose of CBD was 25 mg/kg/day, and the median treatment duration was 48 weeks.
At 12 weeks, adjunctive CBD was associated with a 51% reduction in median monthly convulsive seizures and a 48% reduction in total seizures. Reductions in these seizure types were similar through 96 weeks. At 12 weeks, 52% of patients had a reduction in convulsive seizures of at least 50%, 31% had a reduction of at least 75%, and 11% had a 100% reduction. These response rates were similar through 96 weeks of treatment.
CBD was generally well tolerated. The most common adverse events were diarrhea (29%) and somnolence (22%). About 10% of patients had abnormal liver adverse events, and 75% of them were taking valproate. Among patients taking concomitant clobazam, 38% had somnolence, compared with 14% of patients not taking concomitant clobazam.
The expanded-access program is not placebo-controlled, and neither patients nor investigators are blinded. Furthermore, reporting methods varied between study sites. Despite these limitations, the data indicate that adjunctive CBD significantly reduces seizure frequency, according to the authors.
The data support the results of double-blind, placebo-controlled trials that found that add-on CBD reduces seizure frequency, compared with placebo. The FDA in June approved Epidiolex, the formulation of CBD used in the expanded-access program, for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome.
—Erik Greb
Suggested Reading
Szaflarski JP, Bebin EM, Comi AM, et al. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia. 2018;59(8):1540-1548.
Pooled data from an expanded-access program provide further evidence that adjunctive cannabidiol (CBD) provides meaningful reductions in seizure frequency in patients with treatment-resistant epilepsies. The data were published in the August issue of Epilepsia.
Studies have recently indicated that adjunctive CBD effectively reduces seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. An expanded-access program was created in January 2014 to offer CBD to patients with treatment-resistant epilepsies. Data on safety, tolerability, and efficacy during the first year of the study have been reported. Jerzy P. Szaflarski, MD, PhD, Professor of Neurology at the University of Alabama at Birmingham, and colleagues examined results for safety outcomes at 144 weeks and efficacy outcomes at 96 weeks.
An Expanded-Access Program
All participants in the program had treatment-resistant epilepsy and were receiving stable doses of antiepileptic drugs (AEDs) for at least four weeks before enrollment. During a four-week baseline period, parents and caregivers kept diaries of all countable seizure types. Participants subsequently received a plant-based oral pharmaceutical formulation of CBD (100 mg/mL). Treatment was initiated at a dose of 2–10 mg/kg/day and was titrated to a maximum dose of 25–50 mg/kg/day.
Patients were examined every two to four weeks until the 16th week, and every two to 12 weeks after that point. The efficacy outcomes included the percentage change from baseline in median monthly convulsive seizure frequency and total seizure frequency, and the percentages of patients with at least 50%, at least 75%, and 100% reductions in seizures, compared with baseline. Investigators documented adverse events at each visit.
CBD Was Well Tolerated
The safety analysis included 607 patients, and the efficacy analysis included 580 patients. Among patients included in the safety analysis, 24% withdrew from the study. The most common reasons for withdrawal were lack of efficacy (15%) and adverse events (5%). Participants’ mean age was 13, and 52% of patients were male. The median number of concomitant AEDs was three, the median dose of CBD was 25 mg/kg/day, and the median treatment duration was 48 weeks.
At 12 weeks, adjunctive CBD was associated with a 51% reduction in median monthly convulsive seizures and a 48% reduction in total seizures. Reductions in these seizure types were similar through 96 weeks. At 12 weeks, 52% of patients had a reduction in convulsive seizures of at least 50%, 31% had a reduction of at least 75%, and 11% had a 100% reduction. These response rates were similar through 96 weeks of treatment.
CBD was generally well tolerated. The most common adverse events were diarrhea (29%) and somnolence (22%). About 10% of patients had abnormal liver adverse events, and 75% of them were taking valproate. Among patients taking concomitant clobazam, 38% had somnolence, compared with 14% of patients not taking concomitant clobazam.
The expanded-access program is not placebo-controlled, and neither patients nor investigators are blinded. Furthermore, reporting methods varied between study sites. Despite these limitations, the data indicate that adjunctive CBD significantly reduces seizure frequency, according to the authors.
The data support the results of double-blind, placebo-controlled trials that found that add-on CBD reduces seizure frequency, compared with placebo. The FDA in June approved Epidiolex, the formulation of CBD used in the expanded-access program, for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome.
—Erik Greb
Suggested Reading
Szaflarski JP, Bebin EM, Comi AM, et al. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia. 2018;59(8):1540-1548.