Study: Increased Cardiac Stiffness is Associated with Autonomic Dysfunction in Patients with Temporal Lobe Epilepsy

Autonomic dysfunction is linked to sudden death regardless of the presence of structural heart disease. The pathway from autonomic dysfunction to sudden death is not fully understood, but myocardial sympathetic stimulation leading to arrhythmia and/or cardiac fibrosis might play a role. Our goal was to evaluate cardiac stiffness by echocardiography and its association with clinical, structural, and autonomic variables in people with epilepsy (PWE) compared to healthy controls.

A 12-lead electrocardiogram, treadmill testing, and transthoracic echocardiography from 30 patients with temporal lobe epilepsy (TLE) without any known cardiovascular disorders were compared to 30 individuals without epilepsy matched by sex, age, and body mass index. Distribution of cardiovascular risk factors was similar in both groups. PWE had a higher left ventricle stiffness, left ventricle filling pressure, and greater left atrial volume as well as markers of autonomic dysfunction such as impaired chronotropic index and percentage achieved of predicted peak heart rate at effort. In multiple regressions, autonomic dysfunction explained 52% of stiffness and carbamazepine treatment and polytherapy with antiepileptic drugs (AEDs) explained, additionally, 6% each.

Stiffness is increased in young patients with TLE and is related to autonomic dysfunction and to a lesser extent, carbamazepine use and polytherapy with AEDs.

New Testing Provides Better Information for Parents of Children with Epileptic Encephalopathy

Advances in genetic testing offer new insights to parents who have a child with a rare but serious form of epilepsy, epileptic encephalopathy (EE), found in one of about every 2,000 births and characterized by developmental disabilities as well as horrible seizures.

“New ways of sequencing the human genome mean geneticists and genetic counselors have much more to say to parents who wonder if future children might carry the disease,” says Dr. Heather Mefford, associate professor of pediatrics (genetic medicine) at University of Washington School of Medicine and Deputy Scientific Director of the Brotman Baty Institute for Precision Medicine, co-senior author of findingspublished this week in the New England Journal of Medicine.

A big question from any parent of a child with EE is, “What are the odds that our other children might have this condition?” For decades, parents whose child had epilepsy were told there’s a 1 to 5 percent chance that other children might inherit the mutation. This was based on clinical evidence – the numbers of reoccurrences physicians saw in the clinic.

But armed with more precise testing, the geneticists found parental mosaicism that wasn’t easily detected before in about 10 percent of families, putting these families at higher risk of passing the mutation to another child. What this means in practical terms is that this small group probably accounts for most of the reoccurrences. For some parents, there’s good news: if this parental mosaicism was not detected, your odds of having another such child with epilepsy could be much less than 1 percent.

Zynerba Pharmaceuticals Announces Twelve Month ZYN002 Data from STAR 2 Study in Patients with Focal Seizures at the 2018 Annual Meeting of the American Academy of Neurology (AAN)

Zynerba Pharmaceuticals, Inc., a clinical-stage specialty neuropsychiatric pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments for rare and near-rare neurological and psychiatric disorders with high unmet medical needs, is reporting new longer term open label clinical data today in the Emerging Science session of the 2018 Annual Meeting of the American Academy of Neurology (AAN) in Los Angeles, CA.

In a poster presentation entitled, “Transdermal Cannabidiol (CBD) Gel for the Treatment of Focal Epilepsy in Adults” (poster P4.468), Dr. John Messenheimer presents additional data from ongoing STAR 2 (Synthetic Transdermal CAnnabidiol for the TReatment of Epilepsy) 24-month open label extension study evaluating ZYN002 cannabidiol (CBD) transdermal gel in adult patients with focal seizures. The presentation includes data through twelve months of open label exposure to ZYN002.

The key findings include that responses to ZYN002 in the STAR 2 open label extension, as measured by reductions in focal seizures from the baseline period of STAR 1, are associated with continued treatment with ZYN002. In addition, ZYN002 was shown to be well tolerated through 12 months of treatment in STAR 2.

“These data continue to suggest that focal seizures may be reduced with longer-term exposure to transdermally-delivered CBD,” said Dr. Liza Squires, Zynerba’s Chief Medical Officer. “In this population of patients, the use of ZYN002 for an additional 12 months in STAR 2 was well tolerated and appeared to result in clinically meaningful seizure reductions both across and within the originally randomized STAR 1 groups. These data continue to provide insight into the potential for ZYN002 in certain epilepsies, and we look forward to initiating a Phase 2b study in adult refractory focal seizures in the second half of 2018.”

Zogenix Announces Presentation of New Efficacy and Safety Data from its First Pivotal Phase 3 Clinical Trial of ZX008 in Dravet Syndrome

Zogenix, Inc., a pharmaceutical company developing therapies for the treatment of rare central nervous system (CNS) disorders, today announced additional data from analyses of its first Phase 3 trial (Study 1) of the company’s investigational drug, ZX008 (low-dose fenfluramine hydrochloride), for the adjunctive treatment of seizures associated with Dravet syndrome. Top-line results from Study 1 were previously reported in September 2017. The additional Study 1 results were presented in two late-breaker poster presentations at the Emerging Science session at the 2018 American Academy of Neurology (AAN) Annual Meeting being held April 21-27 in Los Angeles, California (see study data here and here).

As previously reported, Study 1 met its primary objective of demonstrating that ZX008, at a dose of 0.8 mg/kg/day, is superior to placebo as an adjunctive therapy in the treatment of Dravet syndrome in children and young adults based on change in the frequency of convulsive seizures between the 6-week baseline observation period and the 14-week treatment period (p<0.001).

“It is highly encouraging to see that the efficacy and tolerability in this subgroup of patients who had previously failed treatment with stiripentol was comparable to the full Study 1 population,” said Rima Nabbout, M.D., Ph.D., Department of Pediatric Neurology, Reference Center for Rare Epilepsies, and one of the poster’s authors. “As stiripentol is a commonly used antiepileptic drug, it is important to understand how tolerable and effective ZX008 is in this subgroup of patients.”

Study: Usage of EpiFinder Clinical Decision Support Application in the Assessment of Epilepsy

Background: The diagnosis of epilepsy is at times elusive for both neurologists and nonneurologists, resulting in delays in diagnosis and therapy. The development of screening methods has been identified as a priority in response to this diagnostic and therapeutic gap.

EpiFinder is a novel clinical decision support tool designed to enhance the process of information gathering and integration of patient/proxy respondent data. It is designed specifically to take key terms from a patient’s history and incorporate them into a heuristic algorithm that dynamically produces differential diagnoses of epilepsy syndromes.

Objective: The objective of this study was to test the usability and diagnostic accuracy of the clinical decision support application EpiFinder in an adult population.


  • Clinical decision support tools can be implemented in the adult EMU setting.
  • Support tools can adapt to user input creating dynamic epilepsy specific differentials.
  • Algorithms can predict classification between epilepsy and an alternative diagnosis.

Study: Vagus Nerve Stimulation for 6- to 12-Year-Old Children with Refractory Epilepsy – Impact on Seizure Frequency and Parenting Stress Index

OBJECTIVES: Refractory epilepsy (RE) is frequently associated with neuropsychological impairment in children and may disrupt their social development. Vagus nerve stimulation (VNS) had been reported to have beneficial effects on behavioral outcomes. The aim of this study was to compare Parenting Stress Index (PSI) scores before and after VNS device implantation in children with RE, especially those who experienced seizure frequency reduction.

METHODS: We conducted a one-group pretest-posttest study in school age children with RE. Seizure frequency and PSI were recorded at 12months after VNS device implantation.

RESULTS: Treatment with VNS was significantly associated with reduced seizure frequency and parental stress as measured by PSI. Factors contributing to seizure frequency included idiopathic/cryptogenic etiology and neurobehavioral comorbidities. In children with reduced seizure frequency, statistically significant improvements in the child domain of the PSI on the subscales of mood and reinforces parent were found. In the parent domain, the scores for social isolation were reduced.

CONCLUSIONS: Treatment with VNS was significantly associated with reduced seizure frequency and improved PSI scores, especially within the child domain on the mood and reinforces parent subscales. These findings suggest that VNS reduced not only seizure frequency but also the psychological burden on children with RE.

The Epilepsy Foundation Launches a New Research Study to Find Biomarkers for Treatment of Focal Seizures in People with Epilepsy

The Epilepsy Foundation announced on April 24 the launch of a new Human Epilepsy Project study of focal seizures to better understand the long-term challenges of living with focal seizures and determine biomarkers of epilepsy severity and treatment response. The biomarkers research study, HEP2, will monitor 200 people with treatment-resistant focal seizures over a two-year period to measure changes in seizure frequency, treatments used, presence of comorbidities — such as depression and anxiety — healthcare costs, and quality of life. HEP2 is the second in a group of registry-based studies called the Human Epilepsy Project, a joint initiative of the Epilepsy Foundation and the Epilepsy Study Consortium to improve the care of people with epilepsy.

“This new research study is another step in our efforts to better understand focal epilepsy and uncover data that will help accelerate therapies to help people with epilepsy have seizure-free lives,” said Dr. Brandy Fureman, Vice President for Research & New Therapies, Epilepsy Foundation. “We believe HEP2 could have a major impact on prevention strategies, treatments and cures for those who have not responded to current treatments.”

HEP2 is enrolling participants at designated study centers throughout the U.S., including New York, Connecticut, Pennsylvania, Tennessee, Minnesota, and California. The study will also have an international center in Finland. The HEP2 study will follow 200 participants between the ages of 16 and 65 who have a history of focal epilepsy, have four or more seizures per month and have tried four or more drugs to control seizures without success.

Study: Different as Night and Day – Patterns of Isolated Seizures, Clusters, and Status Epilepticus.

Abstract: With the exception of SE in children, our data suggest that more severe patterns favor daytime. This suggests distinct day/night preferences for different seizure patterns in children and adults.

Using approximations based on presumed U.S. time zones, we characterized day and nighttime seizure patterns in a patient-reported database, Seizure Tracker. A total of 632 995 seizures (9698 patients) were classified into 4 categories: isolated seizure event (ISE), cluster without status epilepticus (CWOS), cluster including status epilepticus (CIS), and status epilepticus (SE). We used a multinomial mixed-effects logistic regression model to calculate odds ratios (ORs) to determine night/day ratios for the difference between seizure patterns: ISE versus SE, ISE versus CWOS, ISE versus CIS, and CWOS versus CIS. Ranges of OR values were reported across cluster definitions.

In adults, ISE was more likely at night compared to CWOS (OR = 1.49, 95% adjusted confidence interval [CI] = 1.36-1.63) and to CIS (OR = 1.61, 95% adjusted CI = 1.34-1.88). The ORs for ISE versus SE and CWOS versus SE were not significantly different regardless of cluster definition. In children, ISE was less likely at night compared to SE (OR = 0.85, 95% adjusted CI = 0.79-0.91). ISE was more likely at night compared to CWOS (OR = 1.35, 95% adjusted CI = 1.26-1.44) and CIS (OR = 1.65, 95% adjusted CI = 1.44-1.86). CWOS was more likely during the night compared to CIS (OR = 1.22, 95% adjusted CI = 1.05-1.39).

Serotonin Reuptake Inhibitors May Improve Obstructive Sleep Apnea in Depression With and Without Epilepsy

study of adults with both obstructive sleep apnea (OSA) and depression has demonstrated a link between the use of serotonin reuptake inhibitors (SRIs) and reduced severity of OSA in subjects with and without epilepsy. However, those with epilepsy displayed a more significant correlation between SRI use and reduced severity of OSA. This research was presented at the 70th annual American Academy of Neurology meeting, held April 21-27, 2018, in Los Angeles, California.

The results suggest that SRIs may serve as a potential treatment for OSA and depression, both in patients with and without epilepsy.

Study: The Direct Cost of Epilepsy in Children – Evidence from the Medical Expenditure Panel Survey, 2003-2014

INTRODUCTION: Epilepsy is frequent in children and often requires complex healthcare interventions. There is a paucity of recent and detailed healthcare expenditures among children with epilepsy in the United States (US).

METHODS: Data on children (aged ?17years) from the Medical Expenditure Panel Survey-Household Component (MEPS-HC) from 2003 to 2014 were analyzed. Unadjusted overall and specific cost components were compared between children with epilepsy and those without epilepsy. We used a two-part model with gamma distribution and log link for the estimation of independent incremental cost incurred by epilepsy in children. Unadjusted and adjusted mean expenditures and aggregate burden of epilepsy were estimated.

RESULTS: Out of 54,393,387 (weighted) US children, 457,873 (0.84%) had epilepsy. Children with epilepsy had nearly six times higher healthcare expenditure than those without epilepsy ($2024 [95% confidence interval (CI): 1917-2130] vs. $12,577 [95% CI: 7922-17,231]). Unadjusted inpatient expenditure for epilepsy ($4418 [95% CI: 1550-7285) was ten times higher than that for children without epilepsy, representing more than one-third of unadjusted total direct cost. The adjusted difference in medical expenditure between children with and those without epilepsy was $8317 (95% CI: 3701-13,363). The annual unadjusted aggregate cost of epilepsy in children was approximately $5.8 billion. The annual adjusted difference in cost of epilepsy between children with and those without epilepsy was $3.8 billion.

CONCLUSION: Unadjusted and adjusted medical expenditure among children with epilepsy is high. The high expenditure is essentially driven not only by inpatient expenditure but also by home healthcare, outpatient, and medication healthcare expenditures.