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AES Annual Meeting

Access daily, concise peer-reviewed reports from the AES Annual Meeting selected by the Neurology Today editors

Thursday, February 6, 2020

BALTIMORE—Paroxysmal neurologic events recorded on smartphones were of adequate quality to help doctors assess epilepsy episodes without requiring patients to be observed in the hospital, researchers reported here at the annual meeting of the American Epilepsy Society.

"The video quality was found to be adequate for diagnostic purposes for about 80 percent of patient-generated smartphone videos assessed in our study," said Emily Acton, a medical student at the University of Pennsylvania and a co-author of the poster presentation from the Mayo Clinic OSMARTVIE Study, led by William O. Tatum IV, DO, FAAN, an epileptologist at Mayo Clinic Hospital in Jacksonville, FL.

"Smartphone videos were most predictive of a final video EEG monitoring diagnosis—the gold standard for determining an epilepsy diagnosis—when prominent motor signs were present and when viewed by experts," Acton and colleagues reported.

Working with a $5,000 grant from the Mayo Clinic, researchers from nine academic epilepsy centers performed a prospective trial from 2015–2018 to evaluate the diagnostic utility of patient-submitted smartphone videos of paroxysmal neurologic events.

In the study, Acton and the research team observed videos from 44 patients. The patients' families recorded 530 smartphone videos, which were viewed by expert epileptologists and neurology residents across the sites. The average video lasted about two minutes.

Acton said 30 patients had a final diagnosis of psychogenic non-epileptic attacks, 11 were diagnosed with epileptic seizures, and three patients were determined to have experienced physiologic non-epileptic events. The final diagnoses were determined by video-EEG monitoring after a mean of 3.1 days in hospital.

"The reviewers had no previous knowledge of the patient's medical history," Acton said.

"The patients' families were told in general how to take the videos of an event—to keep the screen focused on the patients and to try to get as much of the patient's body in the picture," Acton explained. "The question was whether the patients' families could take reasonable smartphone videos that could prove useful," she explained. "Overall, it was quite good. About 80 percent of our videos were ranked by our reviewers as having adequate quality."

Acton suggested that the quality of the videos could be improved by instructing families to do a few simple tasks: for example, to try interacting with the patient having a suspected seizure to see if they react, making sure the whole body of the patient is in the screen, and trying to catch the earliest signs of the event, and then following the patients with the video for a little more time even if they suspect the event has passed.

Commenting on the study, Shlomo Shinnar, MD, PhD, FAAN, professor of neurology, pediatrics, and epidemiology and population health at the Montefiore Medical Center and the Albert Einstein College of Medicine, said: "A picture is worth a thousand words, and videos can provide valuable additional information. That said, the reliability of the videos in this study was only moderate. The study also had a very skewed population as 30 of 44 subjects had psychogenic nonepileptic events, which makes generalization difficult."

Danielle Becker, MD, assistant professor of neurology at the Hospital of the University of Pennsylvania, also offered a cautionary note. "I think you have to be careful with this," she told Neurology Today At the Meetings. "I have seen cases in which a person was having a seizure but they didn't look like they were having a seizure, and I have seen cases in which people look like they are having a seizure but they are not. You really need to have an EEG-component to be able to make a definitive diagnosis. Without the EEG you are making a subjective diagnosis; an EEG allows you to be much more objective."

Drs. Tatum, Shinnar, and Becker had no relevant disclosures. Acton also had no relevant disclosures.

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AES Abstract 1.205: Tatum WO IV, Hirsch L, Gelfand M, et al. Video quality using outpatient smartphone videos in epilepsy: Results from the OSMARTVIE Study.

Dr. Tatum IV discussed the study with Neurology Today Editor-in-Chief Joseph E. Safdieh, MD, FAAN in a brief video interview. Watch the video interview with the study author here.

Thursday, December 12, 2019

BALTIMORE—In a small study, infants with tuberous sclerosis treated prophylactically with antiepileptic drugs before seizures occurred appear to have a preserved intelligence quotient compared with infants who were not treated until clinical seizures were diagnosed, researchers reported here at the annual meeting of the American Epilepsy Society.

"This is the first study documenting the long-term efficacy of preventive antiepileptic treatment in children diagnosed with tuberous sclerosis complex," said Sergiusz Jozwiak, MD, PhD, head of the pediatric neurology department at Warsaw Medical University. "Preventive anti-epileptic treatment introduced in infancy reduces the risk of clinical seizures, the number of required antiepileptic drugs, and intellectual disability in school-aged children with tuberous sclerosis complex."

Among 14 children who were given preventive treatment for at least two years when they were first seen with abnormal EEGs, the mean intellectual quotient (IQ) at the last observation—after a mean of eight year's follow-up—was 96, while the mean IQ for the 25 children who were not treated until seizures were observed after a mean of 8.8 years follow-up was 46 (p<0.03),

The parents of children who received standard-of-care treatment from 2000 through 2006 were educated about the signs of seizures. The children received no regular EEG monitoring but were treated with vigabatrin within one week of the onset of seizures.

"We do the first EEG in these children in the first month of life to identify those with tuberous sclerosis," Dr. Jozwiak  told Neurology Today At the Meetings. In the preventive group, recruited between 2006 and 2008, vigabatrin 100- to 150 mg/kg daily—was administered as soon as epileptic discharges were seen on an EEG. The children were monitored with EEG every four to six weeks until age 24 months

Dr. Jozwiak reported that seven of the 14 children given preventive therapy never experienced a seizure; only one of the 25 children in the standard-of-care group has not experienced a seizure (p=0.0001).

The likelihood of a successful withdrawal of antiepileptic drugs was higher in the patients who had preventive treatment—six of 11 children who had drug withdrawal (55 percent) were able to remain drug- and seizure-free compared with four of 24 children (17 percent) in the standard-of-care group (p=0.03), he reported in his poster presentation.

He said that 18 of the 25 children in the standard-of-care group were described as having intellectual disability compared with three of  the 14 children who received preventative therapy (p=0.003).

All of the children in the study were followed through at least 5 years of age.

Commenting on the study, Maria Gieron-Korthals, MD, professor of medicine, pediatric, neurology, and psychology and behavioral neurosciences, at the University of South Florida/Tampa General Hospital, said: "What Dr. Jozwiak is doing is quite new and he is the one who initiated the idea of treating these kids before they have clinical seizures. I definitely would treat these children before they have seizures. It would make sense to treat these children as soon as possible.

"He shows that there is an improvement in IQ in these children if they are treated compared to those who are not treated before they have a seizure. Seizures do contribute to intellectual impairment," Dr. Gieron-Korthals said.

"Treatment of vigabatrin can cause vision problems in children, however,  so if we are treating children with this drug we have to be mindful of that problem," she noted. She also said the results have to be considered with caution because of the low numbers of children in the study.

Drs. Jozwiak and Gieron-Korthals reported no relevant disclosures.

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AES Abstract 1.218: Jozwiak S, Slowinska M, Borkowska J, et al. Preventive antiepileptic treatment reduces risk of intellectual disability and epilepsy severity in tuberous sclerosis complex: Long-term, prospective, controlled trial.

Dr. Jozwiak discussed the clinical importance of the study findings with Neurology Today Editor-im-Chief Joseph E. Safdieh, MD, FAAN. Watch the video interview here.

Thursday, December 12, 2019

BALTIMORE—A slow titration of cenobamate (Xcopri) will likely avoid early discontinuation of the newest drug approved for treatment of partial-onset epileptic seizures, researchers said here at the annual meeting of the American Epilepsy Society.

"Once patients were able to get through the titration phase of treatment with cenobamate in the clinical trials, they didn't have much problem with discontinuation or new adverse events," said William E. Rosenfeld, MD, FAAN, director of the Comprehensive Epilepsy Care Center for Children and Adults in St. Louis, and one of the researchers in the trials.

"Most treatment-emergent adverse events leading to discontinuations occurred during the six-week titration phase of the so-called CO13  and CO17 studies," he said. "We observed that more of these adverse events occurred in the CO17 study, which had a higher dose titration, and it was quickly seen that the titration in the CO17 appeared to be too rapid," he told Neurology Today At the Meetings.

About 100 patients participated in each arm of the studies, and each study had a placebo arm of about 100 patients in each group. The patients, who were about 38-40 years old, =had been diagnosed with epilepsy for at least 20 years. They were experiencing seizures five to 11 times a week depending on the trial arm. More than 80 percent of the patients were taking two or more concomitant medications.

In the trial, concomitant medications could not be changed, but in practice those medication can be altered and that may also reduce adverse events,  Dr. Rosenfeld said.

In the CO13 study, which titrated patients every two weeks, 4.4 percent of the patients discontinued the drug due to adverse events and 1.8 percent of the patients experienced serious treatment-emergent adverse events. In the CO17 study, which utilized a weekly titration schedule, 14.6 percent of patients discontinued due to adverse events, and 6.7 percent of patients experienced treatment-emergent adverse events, Dr. Rosenfeld reported.

"Clearly, the two-week titration schedule was better," he said. "And that may be due to the long half-life of the drug, which ranges from about 30 to 70 hours."

The CO13 study involved a six-week titration course and then an eight-week maintenance phase, and a similar titration time but a 12-week maintenance phase was used for the CO17 study. The CO13 study titrated patients to 200 mg of cenobamate; the CO17 study tested 100 mg, 200 mg, and 400 mg dosages of cenobamate.

"About 71 percent of the adverse events leading to discontinuation occurred during the titration period," Dr. Rosenfeld said.

The adverse events that led to discontinuation were mainly somnolence, dizziness and fatigue, the researchers reported.

Dr. Rosenfeld said that about 85 percent of adults with epilepsy are diagnosed with partial-onset of focal seizures, and those are the patients who are the targets for cenobamate therapy.

He said that the company is planning to release cenobamate on even a slower and lower- dose titration, aimed at also preventing a rare rash that was seen about three times in more than 900 cases with the higher dose titration, but not seen in a lower-dose titration.

"The regimen is planned at 12.5 mg for the first two weeks; then 25 mg for the next two weeks; then 50 mg, and then increases by 50 mg intervals," he said. "It will always be on a two-week increment. We expect to see even fewer adverse events with this schedule."

Commenting on the study, Pavel Klein, MD, clinical professor of neurology at George Washington University and director of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, MD, told Neurology Today at the Meetings: "It was observed during the rapid titration in the CO17 study that the main adverse events of somnolence, dizziness and fatigue occurred early in the titration phase, which is not uncommon with these drugs."

Dr. Klein suggested that using the slow titration of cenobamate will give the patients and the physician a better chance of staying on the treatment. He also noted that another study also indicated that an even slower titration regimen would work even better in mitigating adverse events. He said that study, as discussed by Dr. Rosenfeld, involved starting at 12.5 mg and increasing doses every 2 weeks until achieving the level necessary to prevent seizures.

"I believe this is the route to go in the clinic," he said. Dr. Klein, who has done other work with SK Life Science and other companies in the epilepsy arena, did not participate in the current study.

"There is a general feeling among the investigators that another way to reduce adverse events may be to change some of the concomitant medications, especially if they develop adverse events known to be attributed to other drugs. In many cases if may be sufficient to stop these adverse events by reducing the concomitant drugs or maybe also reducing cenobamate," he said.

Dr. Rosenfeld disclosed relevant relationships with SK Life Sciences, UCB, Isaiah, Synovial, Ortho-McNeil, Take, and his research clinic has worked on almost all epileptic drugs in the last 40 years. Dr. Klein disclosed relevant relationships with SK Life Sciences, Lundbeck, UCB Pharma, Eisai, and Sunovion.

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AES Abstract 1.322: Ferrari L, Rosenfeld WE, Kamin M. Cenobamate adverse events by time of onset and dose from two randomized clinical studies in patients with uncontrolled focal seizures.

Thursday, December 12, 2019

BALTIMORE—Most neonates at-risk for seizures who are undergoing continuous video monitoring are likely to have their first event within the first hour, researchers reported here at the annual meeting of the American Epilepsy Society.

"We wanted to determine if the first hour of video EEG monitoring of at-risk babies was predictive of whether they would have a seizures," Emma Macdonald-Laurs, MBChB, currently an epilepsy fellow at Royal Children's Hospital in Melbourne, Australia, told Neurology Today At the Meetings. Some hospitals will continuously monitor these children for up to 120 hours, Dr. Macdonald-Laurs pointed out.

"We found EEG during the first hour of monitoring in at-risk neonates is highly, but not perfectly predictive of whether seizures will occur over the ensuing 24 hours," she said. "The majority of monitored neonates who go on to have seizures over the next 24 to 120 hours of monitoring do so early on."

Dr. Macdonald-Laurs, who conducted the research when she was a pediatric neurology trainee at Starship Hospital in Auckland, New Zealand, said in her study, 97 percent of the children had their first event within 24 hours. Ninety-eight of the 266 children had seizures, and 55 of them (56 percent) had the first seizure within the first hour of monitoring; 88 percent of the children experienced their first seizure within 10 hours of monitoring.

"It is important to detect the first seizure because it is at the time of the first seizure when you decide whether to treat them," she said.Dr. Macdonald-Laurs noted that all the babies were considered at risk because they had had what was believed to be a seizure or hypoxic ischemic encephalopathy. Of the 266 neonates in the study population,173 were diagnosed with hypoxic ischemic encephalopathy.

Commenting on the study, Julia Jacobs, MD, associate professor of pediatric neurology and director of the pediatric epilepsy program at the University of Calgary in Alberta, Canada, told Neurology Today At the Meetings: "This is a work in progress to determine what the optimum time is to monitor these babies. We would keep monitoring those babies who are atypical until we can figure out why they are exhibiting these seizures," Dr. Jacobs said. "Some of our team members would continue monitoring so they can look at everything, and others of us would use evidence-based science to reduce the time of monitoring."

"We are now looking at monitoring these babies for at least the first 48 hours and discontinuing the monitoring if the EEG is normal after 48 hours," she added. "We have a technician watching these babies online continuously with a physician on-call."

"It is important that we can take them off monitoring as soon as it is safe," she said, "because it is stressful for the families and caregivers to see their baby with these leads on their heads, which can also disturb the skin," Dr. Jacobs said. "Our general feeling is that it might be safe to stop monitoring earlier than we do now. But we haven't systematically done that yet."

Dr. Macdonald-Laurs and Dr. Jacobs disclosed no relevant relationships with industry.

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AES Abstract 1.135: Macdonald-Laurs E, Sharpe C, Nespeca M. Does the first hour of continuous electroencephalography (CEEG) monitoring in at-risk neonates accurately predict subsequent seizures?

Wednesday, December 11, 2019

BALTIMORE—Screening for antibodies, which are present in as many as 9 percent of patients with epilepsy, may help identify potential therapeutic targets in certain populations, researchers suggested here at the annual meeting of the American Epilepsy Society.

In a literature review that included 24 papers, Lisa Gillinder, MBBS, a PhD candidate and clinician researcher at Mater and Princess Alexandra Hospitals of the University of Queensland in Brisbane, Australia, determined that antibodies suggestive of immune causes of disease are found in epilepsy patients about 12.56 percent of the time, and approximately 8.55 percent of the antibodies have been clinically characterized. The papers included in the study represented more than 3,000 epilepsy cases.

In her poster presentation, Dr. Gillinder said the review suggests that patients with an unknown cause of epilepsy-like seizures, drug-resistant epilepsy, or who exhibit temporal features might be targeted for further testing for antibodies.

She said the greatest prevalence of clinically-characterized antibodies were found among patients who were diagnosed with focal epilepsy of unknown etiology, which occurred in approximately 3.80 percent of the patients.

"There has been increasing evidence over the years that immunity can be involved in the onset of some types of seizures, but other than that we really don't know a lot," she told Neurology Today At the Meetings.

The idea that immunity antibodies could play a role in seizures "was extrapolated from cases of encephalitis where patients become really unwell with a cluster of different symptoms, one of which is seizures. From that came the idea for our research: Could antibodies cause seizures as well as some of the epilepsy [cases] we were seeing in our clinic?" she said.

"We did a systematic review of all the literature. Mainly, we found which epilepsy subgroups were most affected by these antibodies," Dr. Gillinder said. "So we included 24 studies that were epilepsy-specific, excluding cases of encephalitis. There was a lot of heterogeneity in the data, and there were no controlled studies, so there is an awful lot of bias that could exist there. We found that across all the patients, at least 8.55 percent had antibodies that could be clinically meaningful."

"In this work, we targeted patients with epilepsy but excluded patients with acute encephalitis, to try to figure out what proportion of our population presenting to our clinic might be affected," Dr. Gillinder said. "Studies have had conflicting results, but our overall impression is that while antiseizure medications often don't work, immune-based therapies can be quite successful. In some cases, patients who have been refractory to treatment have become seizure-free."

The question is, she said, how do we rationalize our screening from an economic standpoint, because it is not practical to screen everyone who walks through the door.

Commenting on the study, Christopher Elder, MD, assistant professor of neurology at Columbia University in New York City, said: "We know that there are some cases of epilepsy that cannot be explained by the usual criteria, and in some of these cases our usual medications are not effective. People have been looking at the role of antibodies in some of these cases."

"In some cases we find antibodies such as the GAD antibody, but we really don't know what to make of this finding at this time. I would not want to order antibody tests routinely because I think we would have a low yield of clinically relevant findings," he said.

"More studies are definitely warranted before we can use these findings in the clinic," Dr. Elder said.

The study was supported by a grant from the American Epilepsy Society. Drs. Gillinder and Elder disclosed no relevant relationships with industry.

Dr. Gillinder discussed the study highlights with Neurology Today Editor in Chief Joseph E. Safdieh, MD, FAAN. Watch the video interview here.

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AES Abstract 1.208: Steriade C, Rickett K, Hartel G, et al. Neural autoantibody frequency in epilepsy—A systematic review and meta-analysis.