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AES Annual Meeting

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

Tuesday, December 8, 2020

Patients diagnosed with focal cortical dysplasias (FCD), malformations of cortical development, often develop epilepsy, which is likely to be medication-resistant, researchers reported at AES2020, the virtual annual meeting of the American Epilepsy Society.

And they may be good candidates for epilepsy surgery, the researchers said.

"Eighty-two percent of 137 patients with FCD in this cohort developed epilepsy," Nathan Cohen, MD, assistant professor of neurology and pediatrics at George Washington University School of Medicine, and attending epileptologist at Children's National Hospital in Washington, DC, told Neurology Today At the Meetings.

"Of those with FCD-related epilepsy, two-thirds are pharmacoresistant," Dr. Nathan said. "We also showed that children with FCD-related epilepsy can benefit from epilepsy surgery. About 35 percent of our cohort had resective surgery and 83 percent of them had Engel I outcome, that is, seizure-freedom or freedom from disabling seizures."

"Neurologists and families should be aware that children with FCD-related epilepsy should be referred for early evaluation by a pediatric epileptologist and consideration for surgical intervention when appropriate," Dr. Cohen said.

For the retrospective cohort study, the investigators identified 137 children who fit the study criteria, accessing their electronic medical records at Children's National Hospital. The average age of those patients included in the study was 11.5 years. Of the children who were diagnosed with FCD, Dr. Nathan said 82 percent developed epilepsy, and 66 percent of these cases proved to be pharmacoresistant.

Of the 112 children with epilepsy, 75 percent were seizure-free at the last visit. Thirty-six percent of that group were seizure-free without surgery but still on anti-seizure medication; 4 percent were seizure-free without surgery and off anti-seizure medication; 28 percent were seizure-free after surgery but still on anti-seizure medication; and 8 percent were seizure-free after surgery and off anti-seizure medication.​

Commenting on the study, Jennifer Hopp, MD, associate professor of neurology and director of the epilepsy division at the University of Maryland School of Medicine, said: “Unfortunately, there remain several challenges to connecting patients with epilepsy surgery evaluations and treatment. These include lack of access to tertiary care epilepsy centers and referrals to specialized epilepsy centers that perform pre-surgical evaluations or that offer surgery."

“In fact, a study in Neurology in 2010 showed that despite the publication of an AAN Practice Parameter in 2003 that recommended referral for epilepsy surgery evaluation after appropriate anti-seizure medication trials, there was a trend to earlier referral but this was not a statistically significant finding," Dr. Hopp said.

“There seem to be several reasons that patients are not referred or sent for epilepsy surgery, despite success rates sometimes above 80 percent," she said. “Some studies have demonstrated that physicians may underestimate the level of disability experienced by patients with regard to seizure frequency or severity. Inaccurate assumptions about the success of surgery, intellectual disability and psychiatric comorbidity as well as older age of the patient have all been factors identified that influence physician referral behaviors. Patient factors certainly also play a role and early and clear discussion of the risks and benefits of epilepsy surgery for that individual are paramount in the patient decision-making process."

“Surgical therapy for FCD can be very effective," Dr. Hopp continued. “FCD is classified in different types, she said, and outcomes after resection of FCD may vary by type, but with a thorough evaluation and testing, patients may do quite well after surgical treatment."

Drs. Cohen and Hopp had no relevant disclosures.

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AES Abstract 97: Cohen N, Havens K, Whitehead M, Gaillard W. A natural history study of epilepsy in pediatric focal cortical dysplasia.​​


Tuesday, December 8, 2020

Almost half of patients with newly diagnosed focal epilepsy have experienced a mood disorder, anxiety disorder, or both, and approximately a quarter of these patients present with suicidality, researchers reported at AES2020, the virtual annual meeting of the American Epilepsy Society.

The findings underscore the need for vigilance about mental health issues for epilepsy right at the time of diagnosis, the research team said. Patients with epilepsy have a risk of death by suicide that is 10 times higher than the general population, and mood and anxiety disorders have been linked with suicidal thoughts and behavior.

“In neurology, we are now starting to appreciate the importance of recognizing psychiatric comorbidities," said the presenting author Andres M. Kanner, MD, FAAN, director of the International Comprehensive Epilepsy Center at the University of Miami Miller School of Medicine. “For a long time, these were something that nobody paid attention to."

Researchers pulled data for 366 people newly diagnosed with non-lesional focal epilepsy—those who had been treated with antiepileptic medications for less than four months—from the Human Epilepsy Project, a group of more than 300 doctors, researchers, health care workers, and patients working internationally to study biomarkers in new-onset epilepsy. They identified mood and anxiety disorders using the MINI International Neuropsychiatric Interview. Also, they assessed current and lifetime active suicidal ideation and suicide attempts using the Columbia Suicide Severity Rating Scale.

They found 162 of the subjects—or 44.3 percent—met the criteria for a mood, anxiety disorder, suicidality, or any combination of these; 143 subjects had a mood or anxiety disorder, or both —and 14 percent did have both.

They observed major depressive disorder in 9.5 percent of the patients, and bipolar disorder in 8.5 percent. The most common anxiety disorder was generalized anxiety (14.5 percent), followed by panic disorder (12 percent). Ten percent of patients had more than one type of anxiety disorder.

Eighty-two patients (22.4 percent) met the criteria for active and/or passive suicidal ideation or they had made a suicide attempt. Fourteen percent had experienced suicidal ideation at some point in their lifetime, and 5 percent of patients had active suicidal ideation within the previous six months. Seventeen patients, or 4.6 percent, had made a suicide attempt at some point in their lives.

Bipolar disorder was most closely associated with lifetime suicide attempts, with an odds ratio of 22.4 compared to those without bipolar disorder (p=0.0001), followed by major depression with an OR of 17.3 (p=0.0001). Panic disorder was the strongest predictor of current suicidal ideation (OR = 12.9; p=0.0001). Lifetime suicidal ideation was also predicted most strongly by panic disorder (OR = 14.6; p=0.0001).

“Very often, people think of these comorbid conditions as a consequence of chronic epilepsy, and our data show a significant number of people, by the time they are diagnosed with epilepsy, may have already been suffering from these conditions," Dr. Kanner said. “And you have to identify them on the first visit when you're evaluating these patients for epilepsy."

When these disorders are found, he said, that can have important implications for treatment.

“You need to factor in these psychiatric disorders into the selection of your antiepileptic medication," Dr. Kanner said. Someone with a history of depression shouldn't be prescribed a medication with negative psychotropic properties, he added.

Dr. Kanner noted the data also show the relatively high frequency with which these patients ponder or attempt suicide.

“Twenty-five percent of patients already have experienced suicidal ideation by the time the epilepsy is diagnosed," he said. “It's something you have to recognize."​

Gregory L. Krauss, MD, professor of neurology at Johns Hopkins, said the findings are cause for exploring these connections more deeply.

“The study shows a strong relationship between mood and anxiety disorders and having suicidality symptoms in patients with newly diagnosed focal epilepsy," he said. “The high proportion with suicidality (22 percent) and suicidal attempts (4.6 percent) in this group is striking and should be explored further, including biological effects of focal epilepsy on mood and anxiety."

​Dr. Kanner has no relevant disclosures. Dr. Krauss has received fees for consulting for Arvelle Labs and SK LifeScience.

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AES Abstract 970: Kanner A, Kim DH, Anita S, et al. Which of the mood and anxiety disorders are the strongest predictors of suicidality in newly diagnosed non-lesional focal epilepsy?


Tuesday, December 8, 2020

A novel voxel-based MRI method that assessed multiple modalities helped identify lesions in patients with focal epilepsy that had been missed on traditional MRI, according to a study presented at AES2020, the virtual annual meeting of the American Epilepsy Society.

The technique identified lesions in approximately two-thirds of those who previously had had negative MRI scans.

“The hope would be to have this implemented far down the road in helping to detect lesions in MRI negative patients," said Jonah Isen, BComp, an undergraduate researcher at Queen's University in Ontario, Canada, who presented the findings. “At this point, if you're MRI-negative and medicine is not working to help curb your epilepsy, then you may need some sort of invasive testing to figure out where the lesion is so that you can proceed with surgery. So this will hopefully eliminate the step of invasive testing."

Voxel-based morphometry—which uses three-dimensional data points to assess the brain—and the MRI modalities used are not new. But the investigation of  several modalities in a comparative study is novel, he continued.

“Some of these modalities hadn't been researched before for voxel-based analysis," Isen said.

Subjects included 62 healthy controls, 44 people with epilepsy and lesions visible on MRI scans, and eight people with epilepsy whose MRI scans appeared normal.

About a third of the time, the MRI scans of people with refractory focal epilepsy appear normal, Isen explained.

The experimental protocols involved a basic T1-MRI scan, along with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), an advancement of diffusion weighted imaging that allows better visuals of microstructures such as dendrites and axons.

The different images are co-registered to the person's T1 scan, the most detailed of the scans. Then, through a process of normalization, the images' sizes and shapes are morphed to a template to make an apples-to-apples comparison possible.

“Once the brains are the same shape and the same size, it's a matter of performing statistical tests on them to see which areas of the brain are statistically different from the control brains," Isen said.

Researchers found that the decreased neurite density index (NDI)—the image that reflected a decrease in the signal intensity of NDI compared to a regular brain—produced the most useful imaging. NDI, a parameter derived from NODDI, refers to imaging that represents the density of neurites. This modality accurately detected 76 percent of the lesions of the epilepsy patients with visible lesions on MRI and 63 percent of the lesions of those with epilepsy who had had an MRI scan that appeared normal.

Their next step is to detect lesions using the combination of several modalities at once, in the hope that the accuracy of detection improves even further, Isen said. The approach is far from being able to be used clinically, but these findings represent an important step in that direction, he said.

Kathryn Davis, MD, assistant professor of neurology at the University of Pennsylvania Perelman School of Medicine, who was not involved with the study, said the approach is promising.

“If NODDI is able to identify a clear lesion on MRI, a more directly therapeutic approach could be taken," she said. “For instance, a patient may be able to have more targeted intracranial EEG placement or proceed directly to surgical intervention."

But she said the technique needs more study.

“It is feasible to obtain NODDI imaging on clinical 3T MRI scanners. However, the scan times are longer than typical clinical scans," she said. “The data presented here is from a very small number of patients and it is unclear what the false positive rate is for lesion detection with NODDI in patients without visible lesions on conventional MRI. A multicenter study including a larger number of patients is needed to determine the scalability of NODDI in clinical care."

Orrin Devinsky, MD, FAAN, the director of the New York University Langone Comprehensive Epilepsy Center, agreed that the findings were a positive step.

These findings “are encouraging and reflect a growing interest in advancing imaging and machine-learning techniques to improve detection of subtle abnormalities that escape detection by the human eye and mind," he said.

“This study highlights progress using voxel-based morphology and the neural density index.  The key for this and similar work is validating this in patients who undergo epilepsy surgery to resect or ablate or stimulate the areas identified and compare long-term outcomes to those in which no such lesions are found," Dr. Devinsky told Neurology Today At the Meetings.

Isen had no relevant disclosures.

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AES Abstract 67: Isen J, Perera-Ortega A, Vos S, et al. Voxel based analysis of multimodal MRI for brain lesion detection in focal epilepsy.

Tuesday, December 8, 2020

Neonatal seizures rarely result in an epilepsy diagnosis by 2 years of age, but seizures that persist into early childhood are associated with a high risk of neurodevelopmental problems, according to a multicenter study presented at AES2020, the virtual meeting of the American Epilepsy Society.

In this multicenter study of infants who survived acute symptomatic neonatal seizures, 13 percent had post-neonatal epilepsy by age 24 months. Although half were seizure-free for at least six months at last follow-up, 80 percent had clearly abnormal development, said the lead study author Renée Shellhaas, MD, clinical professor of pediatrics at the University of Michigan in Ann Arbor and director of research in the division of pediatric neurology at Michigan Medicine.

The researchers assessed 282 infants who were born between July 2015 and March 2018 at nine neonatal seizure registry sites. All infants had acute symptomatic neonatal seizures.

Infants with neonatal onset epilepsy syndromes were excluded.

The investigators evaluated post-neonatal functional development and epilepsy at ages 12, 18, and 24 months using the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) scale. By 24 months, 37 of the 282 children who had experienced neonatal seizures were diagnosed with epilepsy.

Dr. Shellhaas said that 80 percent of the children who developed epilepsy had WIDEA-FS scores worse than two standard deviations below the normal population mean.

“Additionally, up to a third of infants who developed epilepsy had treatment-resistant, frequent daily seizures. This shows a broad range of epilepsy outcomes—from no epilepsy in the majority to treatment-resistant epilepsy in a high-risk few," she told Neurology Today At the Meetings.

Risk factors for post-neonatal epilepsy included EEG-confirmed seizures on multiple days and an abnormal neurological examination upon discharge from a neonatal seizure admission, Dr. Shellhaas noted. “Families whose children have these risk factors should be specifically counseled about infantile seizure semiologies—focal seizures and infantile spasms, in particular."

“Nine of the 37 infants who developed epilepsy in our cohort already had epilepsy by the time they reached the age of 3 months," she said. “In addition, most of the infants who had an abnormal EEG at 3 months did not go on to develop epilepsy. Therefore, we found that a routine EEG at age 3 months does not seem to be clinically helpful for screening for post-neonatal epilepsy risk."

Notably, five infants already had hypsarrhythmia on their three-month EEGs, which indicates a very high risk for infantile spasms, Dr. Shellhaas said. “We suggest that infants with risk factors—especially neonatal seizures on three or more days, and/or severely abnormal EEG backgrounds, and abnormal neurological examinations, as well as those with brainstem or basal ganglia injury—should be followed especially closely by their pediatrician and child neurologist. Waiting until 3 months of age to follow-up with a child neurologist is too long for many of these high-risk infants."

“One of the strengths of this study is that all of the seizures were confirmed to be seizures," commented Dennis Dlugos, MD, professor of neurology and pediatrics at the University of Pennsylvania Medical School, who was not involved with the study. “No previous prospective studies have confirmed that a sick newborn is having EEG-confirmed seizures. In older literature, it has sometimes been difficult to determine what was a clinical neonatal seizure, but we know that clinical identification of neonatal seizures is difficult, and without EEG confirmation it is hard to know who is having a seizure or not."

 “The good news is that just one in 7.5 of these children with neonatal seizures will go on to have epilepsy," he said. “The bad news is that one in 7.5 of these children will go on to have epilepsy, so whether that 13 percent rate is considered high or low depends upon your perspective."

“The children in this study had what we call provoked seizures, that is, they were provoked by an underlying cause such as hypoxic ischemic encephalopathy, head trauma, bleeding, infection, or metabolic abnormalities. Epilepsy is defined as unprovoked seizures," noted Dr. Dlugos.

“Here, the acute or unprovoked symptomatic seizures were studied to see how many of them went on to develop epilepsy," he said. “The seizures being studied in this presentation are symptoms of an underlying condition. In these children, we try to minimize the injury, but reversing the injury is a lofty goal. In neonatal care, we are trying to reverse or minimize the injury."

Dr. Dlugos said that the bottom line for parents is that the child “in most cases will not go on to have epilepsy. The 87 percent figure is good, we would like it to be better, but that is encouraging news. The other encouraging news is that if the kids do develop epilepsy most respond to treatment."

Drs. Shellhaas and Dlugos had no relevant disclosures.  

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AES Abstract 99: Shellhaas R, Wusthoff C, Numis A, et al. Early-life epilepsy after acute symptomatic neonatal seizures—A prospective multicenter study.