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Neuro-News Roundup: Epilepsy – Latest Literature and Expert Perspectives

Get caught up on some of the latest news in epilepsy and seizure disorders, with data updates and expert insights, all in one place from the NeurologyLive® team.

In recent weeks and months, the NeurologyLive® team has been hard at work conducting interviews with experts and covering the news on the latest updates in the clinical care of individuals with epilepsy and seizure disorders, including those with various epilepsy types and rare syndromes such as Dravet syndrome and Lennox-Gastaut syndrome.

To offer an update on those new developments in the literature and insight into the expert opinions about how they’re shaping the ever-changing care paradigm in movement disorders, our team has compiled some of the biggest pieces of news and exciting exchanges with physicians into one place.

Click here for more coverage of the latest epilepsy and seizure disorder news from NeurologyLive®.

EXPERT INSIGHTS

Elia Pestana-Knight, MD, a pediatric epileptologist at Cleveland Clinic, was the lead investigator for the Marigold study (NCT03572933) of ganaxolone in patients with CDKL5 deficiency disorder (CDD). She presented the latest data at the 2022 American Academy of Neurology (AAN) Annual Meeting. Although the disease has only been formally recognized for about 20 years, several prominent neurology-based organizations have begun to understand the importance of addressing it. In an interview with NeurologyLive®, she broke down the types of research needed to advance the state of care for CDD, along with some of the major efforts currently underway.

Kelly Knupp, MD, associate professor of neurology and epilepsy specialist at Children’s Hospital Colorado, was the lead investigator on the phase 3 Study 1601 (NCT03355209) of the recently approved fenfluramine (Fintepla; Zogenix) in patients with a rare childhood epileptic encephalopathy, Lennox-Gastaut syndrome (LGS). Knupp told NeurologyLive® that her personal experiences with titrating patients have proven to be more effective uses of the treatment. She also broke down the open-label data in detail, highlighted some of the most notable findings, and shared some of the positive aspects of fenfluramine the LGS community may not yet be aware of regarding its use as a therapy.

Jacqueline A. French, MD, professor, department of neurology, NYU Langone Health Center, and codirector, Epilepsy Clinical Trials, NYU Langone, Comprehensive Epilepsy Center, spoke with NeurologyLive® about another therapy that might help drive down the number of individuals with refractory epilepsy, called XEN1101. Treatment-resistant, or refractory, epilepsy has stood in the way of quality of life for patients and has proven to be a challenging obstacle for physicians in the field, and despite efforts, the number of patients with refractory disease has been mostly maintained. French also discussed her hopes for the future in drug development for treatment-resistant epilepsy that includes therapies that are disease-modifying rather than merely symptomatic, pointing to the reclassification of current agents to antiseizure medications from the older term, antiepileptic drugs, as a sign of that shift in thinking.

Ashwini Sharan, MD, the vice-chair of clinical operations in neurosurgery at the Vickie & Jack Farber Neuroscience Institute of Jefferson University Hospital, recently sat down with NeurologyLive® along with his colleague Chengyuan Wu, MD, MSBmE, for a roundtable discussion on all things deep brain stimulation. A portion of that conversation covered the neurosurgical approach for epilepsies, including the challenge in raising awareness about this method's potential as a treatment option.

LATEST LITERATURE

EEG Changes in Acute Phase of Autoimmune Encephalitis May Predict Risk of Drug-Resistant Epilepsy

A new retrospective analysis showed that drug-resistant epilepsy (DRE) was uncommon in those with autoimmune encephalitis (AE) at 12-month follow-up, but was associated with several risk factors, including the presence of status epilepticus (SE) during acute admission and multiple biomarkers of neuronal dysfunction on electroencephalography (EEG).1

The first objective of the study, identifying the prevalence of DRE, was observed in 16% of the 69-patient cohort who were retrospectively followed up at 12 months. Lead investigator Robb Wesselingh, MBBS, neuroimmunologist, Monash University, and colleagues concluded that the "identified biomarkers provide the basis to generate a clinically applicable prediction tool which could be used to inform treatment, prognosis, and patient selection for clinical trials." They also noted that EEG is a noninvasive and accessible tool that can serve as a potentially useful biomarker for disease prognostication.

Long-Term Cenobamate Data Show Sustained Seizure Reductions, Including Total Seizure Freedom

Newly published data from the long-term, open-label extension (OLE) of the randomized, placebo-controlled C017 study (NCT01866111) of cenobamate (Xcopri; SK Life Sciences) showed that the antiseizure medication (ASM) sustained efficacy after 48 months, upward of 15% of individuals achieving 100% seizure freedom.2,3

Cenobamate was evaluated in a cohort of 355 patients, aged 18 to 70 years, with uncontrolled focal seizures who completed the 18-week double-blind study. Despite failing 1 to 3 previous antiseizure medications, 16.4% and 39.1% of patients achieved 100% or at least 90% seizure reduction, respectively, during months 36 through 48.

Pavel Klein, MD, epileptologist and neurologist, Mid-Atlantic Epilepsy and Sleep Center, Bethesda, Maryland, said in a statement,2 "We were pleased to see these results in such a difficult-to-treat patient population. More than three-quarters of patients treated with cenobamate experienced a reduction in seizure frequency of 50% or more during years 3 to 4 of the study. Physicians may want to consider whether patients with partial-onset (focal) seizures are appropriate candidates for adjunctive treatment with cenobamate."

Periconceptional Folic Acid Supplementation Decreases Risk of Preterm Birth in Epilepsy

Findings from the prospective Norwegian Mother and Child Cohort Study showed that among women with epilepsy on an ASM, periconceptional folic acid supplementation was associated with a lower risk of preterm birth. All told, there was a 3-fold increase in the risk among those who did not undergo supplementation vs those who did.4

To evaluate whether folic acid supplementation was associated with primary outcomes such as preterm birth (gestational age <37 weeks at birth), small for gestational age (SGA), and preeclampsia, investigators evaluated 100,105 singleton pregnancies from 1999-2008. In 764 of these pregnancies, the mother had a diagnosis of epilepsy; 316 mothers were exposed to ASM during pregnancy and 358 were not.

Folate has been shown to be essential for DNA synthesis, and the demand for folate increases during pregnancy due to uterine, placental, and fetal growth, the investigators noted. Silje Alvestad, MD, PhD, postdoctoral fellow, University of Bergen, and colleagues wrote, "Our study supports the recommendation that ASM-treated women with epilepsy with a potential to become pregnant should use daily folic acid supplement. The optimal dose of folic acid remains unknown and likely varies between ASMs and between individual women."

Despite Quality-of-Life Improvements, Cognitive Issues Linger Post Epilepsy Surgery

Results from a retrospective study showed that epilepsy surgery has positive impacts on employment status and ASM use; however, errors in executive function tasks and poorer working memory postsurgery were associated with worse employment status.5

Following epilepsy surgery, there was no change in employment status for 58.7% of patients, whereas 21.7% improved their employment status. At 6 months postoperation, the final model included 5 cognitive variables—age, education in years, word list immediate recall, the number of uncorrected executive function mistakes, and block design—that were associated with improved employment status.

"From a clinical perspective, our data suggest that postoperative neuropsychological assessments of epilepsy surgery patients should utilize aggregate measures across several tests to reveal subtle difficulties. For the patient with epilepsy’s wellbeing, even small difficulties in executive function may make challenging jobs more demanding than they are for individuals without epilepsy and result in poorer quality of life in general," author Eino Partanen, PhD, MSc, cognitive neuroscientist, University of Helsinki, and colleagues wrote.

REFERENCES
1. Wesselingh R, Broadley J, Buzzard K, et al. Prevalence, risk factors, and prognosis of drug-resistant epilepsy in autoimmune encephalitis.Epilep & Behav. 2022;132:108729. doi:10.1016/j.yebeh.2022.108729.
2. Long-term efficacy and safety data of Xcopri (cenobamate tablets) CV published in Neurology. News release. SK Life Science. June 22, 2022. Accessed June 27, 2022. https://www.sklifescienceinc.com/pdf/Long_Term_Efficacy_and_Safety_Data_of_XCOPRI%C2%AE_cenobamate_tablets_CV_Published_in_Neurology.pdf
3. Klein P, Aboumatar S, Brandt C, et al. Long-term efficacy and safety from an open-label extension of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. Published online June 15, 2022. doi:10.1212/WNL.0000000000200792
4. Alvestad S, Husebye ES, Christensen J, et al. Folic acid and risk of preterm birth, preeclampsia and fetal growth restriction among women with epilepsy: a prospective cohort study. Neurology. Published May 16, 2022. doi:10.1212/WNL.0000000000200669
5. Partanen E, Laari S, Kantele O, Kamppi L, Nybo T. Associations between cognition and employment outcomes after epilepsy surgery. Epilep & Behav. 2022;131:108709. doi:10.1016/j.yebeh.2022.108709