Study Shows Novel Mobile Technology Improves Quality of Life for Adults with Epilepsy

In an externally-funded grant, CURE PTE Initiative investigators Dr. Jeffrey Loeb, Dr. Dilip Pandey, and Research Associate Jessica Levy investigate the ways technology can improve outcomes in individuals living with epilepsy

Abstract

Purpose: People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QoL), and personal impact of epilepsy in adults with epilepsy.

Methods: Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Epilepsy.com. Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8–12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2).

Results: The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in most SM measures from T1 to T2.

Conclusion: This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QoL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE.

Assessing the Personal Impact of Epilepsy in a Population-Based Cohort of Veterans

PURPOSE:

Epilepsy impacts patient lives in multidimensional ways. Although previous work has investigated epilepsy impact on health status, little is known about the overall quantified impact of epilepsy in Veterans. The goal of this study was to describe the impact of epilepsy on Veterans’ lives using the Personal Impact of Epilepsy Scale (PIES) and determine the patient and clinical characteristics most strongly correlated with epilepsy impact. The researchers described cohort characteristics and developed regression models to determine which characteristics were most strongly associated with PIES subscale (seizure, medication, comorbidity) scores and quality of life (QOL).

RESULTS:

Approximately 36% of those who were invited responded to the survey. Of the 438 respondents included in the analyses, roughly 50% were aged 45-64 years (35% >65; 14% 18-44); 19% were women. Almost 90% had previously received care by an epilepsy specialist, 37% of which was in Veterans Health Administration (VHA) and 38% in both VHA and community. The PIES overall and subscale scores were significantly lower for older Veterans with epilepsy (VWE) (>65) compared with younger (18-44 years) and middle-aged (45-64 years) VWE, indicating that older Veterans had a lower epilepsy impact overall, and for seizures, medication, and comorbidity.

The younger and middle-aged VWE had a significantly higher proportion with psychiatric diagnosis compared with older VWE. There was a trend for significance for the overall PIES scores by gender, with women having total higher (worse) scores (mean = 93.10, SD = 69.68) than men (mean = 74.39, SD = 59.97), which was driven by a statistically higher score on the seizure subscale for women (mean = 27.66, SD = 27.97) compared with men (mean = 9.29, SD 25.35). Regression models revealed that frequent seizures (>1/month, >2/month) and diagnoses of dementia significantly predicted higher (more negative) Seizure Severity PIES score. Frequent seizures (>1/month), number of antiepileptic drugs (AEDs), and diagnosis of dementia predicted negative impact, and older age predicted positive impact for medication subscale. Frequent seizures (>1/month) and diagnoses of depression and dementia predicted negative mood and social impact. Seizure frequency (>2/month) was the only variable that significantly predicted lack of excellent quality of life. Effects for gender were not significant after controlling for other variables.

CONCLUSIONS:

Findings were similar to a prior study of generic health outcomes in younger and older VWE using the 36-Item Short Form Survey (SF-36). Seizure frequency was consistently associated with negative impact of epilepsy in all age groups. While dementia and other diagnosed health conditions also contributed to epilepsy impact, older VWE (veterans with epilepsy) had significantly lower PIES (Personal Impact of Epilepsy Scale) scores even after controlling for physical conditions and dementia. Lower (better) scores for comorbidity and medication scales in older VWE may be due to fewer diagnosed psychiatric comorbidities and psychiatric medication that have similar cognitive impact as AEDs (antiepileptic drugs), and which may also interact with AEDs. Implementation of patient self-management programs to improve seizure control may reduce epilepsy impact for Veterans and reduce Veterans Affairs (VA) healthcare utilization. The PIES may also be useful to measure outcomes of self-management interventions.

Study Looks at Risk Factors for Post-Traumatic Epilepsy in Pediatric Traumatic Brain Injury Patients

In a pediatric traumatic brain injury (TBI) population treated in an intensive care unit (ICU), researchers identified the clinical and radiological risk factors correlated with posttraumatic epilepsy (PTE). Between 2003 and 2013, the Finnish Intensive Care Consortium database were used to identify pediatric (<18 years) TBI patients treated in four academic university hospital ICUs in Finland. Utilizing multivariable logistic regression modeling, the risk factors associated with PTE were evaluated. Fifty-nine patients developed PTE of the 290 included in the study. Findings suggested that PTE is a common long?term complication after ICU?treated pediatric TBI.

An increased risk of PTE is associated with higher age, moderate severity of injury, obliterated suprasellar cisterns, seizures during ICU stay and surgical care.

Repurposed Molecules for Antiepileptogenesis: Missing an Opportunity to Prevent Epilepsy?

Prevention of epilepsy is a great unmet need. Acute central nervous system (CNS) insults such as traumatic brain injury (TBI), cerebrovascular accidents (CVA), and CNS infections account for 15%-20% of all epilepsy. Following TBI and CVA, there is a latency of days to years before epilepsy develops. This allows treatment to prevent or modify post-injury epilepsy. No such treatment exists. In animal models of acquired epilepsy, a number of medications in clinical use for diverse indications have been shown to have antiepileptogenic or disease-modifying effects, including medications with excellent side effect profiles. However, except for vigabatrin, there have been almost no translation studies to prevent or modify epilepsy using these potentially “repurposable” medications. Doctors may be missing an opportunity to develop preventive treatment for epilepsy by not evaluating these medications clinically.

One reason for the lack of translation studies is that the preclinical data for most of these medications are disparate in terms of types of injury, models within different injury type, dosing, injury – treatment initiation latencies, treatment duration, and epilepsy outcome evaluation mode and duration. This makes it difficult to compare the relative strength of antiepileptogenic evidence across the molecules, and difficult to determine which drug(s) would be the best to evaluate clinically. Furthermore, most preclinical antiepileptogenic studies lack information needed for translation, such as dose – blood level relationship, brain target engagement, and dose-response, and many use treatment parameters that cannot be applied clinically, for example, treatment initiation before or at the time of injury and dosing higher than tolerated human equivalent dosing.

Here, this research team reviews animal and human antiepileptogenic evidence for these medications. The team highlights the knowledge gaps for each molecule that need to be filled in order to consider clinical translation, and we suggest a platform of preclinical antiepileptogenesis evaluation of potentially repurposable molecules or their combinations going forward.

CURE Initiative: Defending Against Post-Traumatic Epilepsy

A graphic which states, "CURE and the Department of Defense. From 2000-2019, over 400,000 US service members were diagnosed with a TBI."Post-traumatic epilepsy (PTE) is a seizure disorder resulting from injury to the brain. It is a devastating complication of traumatic brain injury (TBI), which can occur as a result of car accidents, sports-related injuries, or military combat. PTE can develop weeks, months, or even years after TBI, offering a window of opportunity for interventions to prevent seizures. Unfortunately, there is currently no way to predict who will develop epilepsy following TBI, and there are no therapies to prevent it.

CURE’s collaborative, multi-investigator PTE research program aims to develop better models to study PTE and discover methods to predict who is at risk as a way to intervene early and prevent PTE. With a $10 million grant from the US Department of Defense, this initiative brings together leading scientists in the field from around the world. This groundbreaking initiative, which launched in 2018, involves six primary investigators and their research teams for a total of over 60 scientists. To further encourage collaboration and scientific rigor, CURE has contracted with the Laboratory of Neuro Imaging (LONI) at the University of Southern California to create a database to house data from the teams and make it accessible for cross-comparison and analysis.

These teams are enhancing knowledge about PTE by researching what changes occur in the brain, as well as by developing robust animal models to study PTE. In addition, the researchers are investigating how different types of head injury can contribute to seizure onset and occurrence, and they are identifying potential EEG, MRI, or blood biomarkers to predict PTE in humans.

One exciting, ongoing PTE project is led by Dr. Jeffrey Loeb of the University of Illinois at Chicago. Dr. Loeb’s team project will focus on a type of bleeding commonly caused by TBI called subarachnoid hemorrhage. This kind of bleeding occurs when there is blood between the brain and the protective tissue surrounding the brain. By studying both rat models and in-patient instances of subarachnoid hemorrhage, Dr. Loeb’s data-driven approach will hopefully lead to methods or guidelines to help doctors take steps to prevent the development of epilepsy. Check out our recent interview with him to learn more.

We’ve also seen significant achievements over the course of the past two years. These includes a publication from Dr. Harald Sontheimer’s team at Virginia Tech University on a new mouse model for PTE,1 and a manuscript in preparation by Dr. Victoria Johnson’s team at the University of Pennsylvania on neuropathology in humans after TBI. The investigators have presented abstracts of their work at scientific meetings including the 2019 National Neurotrauma Society meeting in Pittsburgh, PA and the 2019 American Epilepsy Society Meeting in Baltimore, MD.

This collaborative, team-science approach has the potential to develop innovative ways to study PTE, build understanding of the neural mechanisms behind PTE, and ultimately help us understand who is at the greatest risk. This research can pave the way for the development of therapies to prevent and/or treat PTE, having a positive impact on the lives of all affected by TBI and PTE.

1 Shandra O., Robel S. Inducing Post-Traumatic Epilepsy in a Mouse Model of Repetitive Diffuse Traumatic Brain Injury. J Vis Exp. 2020 Feb 10;(156)

Learn More about PTE

Mike and Kim Adamle smiling as they are being interviewed for an episode of Seizing Life, a CURE podcast

Podcast: Former football star and broadcaster Mike Adamle discusses developing and managing PTE resulting from sports injuries.

Watch or Listen Now

Woman sitting at a laptop participating in a CURE webinar.

Webinar: Watch a free webinar on what triggers seizures in people who sustain traumatic brain injury.

Watch Now

Dr. Graffman being interviewed by Kelly Cervantes, CURE Board Member and Seizing Life podcast host.

Podcast: Explore the relationship between TBI and PTE, particularly in Vietnam veterans, in this Seizing Life podcast episode.

Watch or Listen Now

Woman standing in a research lab wearing a white coat with her back to the camera.

CURE Discovery: Discover the results of an innovative CURE-funded study aiming to find a way to prevent PTE.

Learn More

Epilepsy Research Findings: March 2020

This month’s research highlights feature promising work by former CURE Grantees and CURE partners.

Former CURE Grantee Dr. Kristina Simeone’s recent research has uncovered a potential predictive biomarker for Sudden Unexpected Death in Epilepsy (SUDEP). Dr. Simeone’s work was supported by the Benninghoven family in memory of Cameron Benninghoven.

We also feature research by another former CURE Grantee, Dr. Angelique Bordey, who along with her research team published exciting findings showing that targeting a particular protein in the brain can reduce or prevent seizures in mouse models of difficult-to-treat epilepsy.

We are also highlighting research by Dr. Daniel Correa and his work through the EpiBioS4Rx Public Engagement Core, a project in which CURE participates. Dr. Correa’s research indicates that greater efforts should be made to ensure online epilepsy health education materials are more easily understandable to the general population to increase epilepsy literacy.

These findings, as well as others, can be found below:

Research Discoveries & News

  • SUDEP: Research featuring the work of former CURE Grantee Dr. Kristina Simeone found a potential time-based biomarker of impending SUDEP. Dr. Simeone found cardiac and respiratory dysfunction that changed over time in mice at risk for SUDEP and may serve as a biomarker to indicate who is at risk for SUDEP. She also found that this dysfunction could be lessened by blocking a particular type of receptor in the brain, the orexin receptorLearn More

    This research was supported by the Benninghoven family in memory of Cameron Benninghoven.

  • Uncontrolled Epilepsy Treatment: Former CURE Grantee Dr. Angelique Bordey and her research team utilized an experimental drug to reduce seizures in mouse models of tuberous sclerosis complex (a rare genetic epilepsy) and a subset of focal cortical dysplasia type II (a brain malformation causing epilepsy). The team found that seizures can be prevented or reduced by targeting a protein called actin-cross linking protein filament A which is often elevated in the brains of humans with these epilepsies. Learn More
  • Online Epilepsy Education: Researcher Dr. Daniel Correa found that the majority of online health education materials related to traumatic brain injury (TBI), epilepsy, and post-traumatic epilepsy (PTE) do not meet the sixth-grade reading level recommendation from most health organizations. This study was published as part of the CURE-supported EpiBioS4Rx Public Engagement Core, an NINDS initiative focused on ensuring successful future clinical trials to prevent the development of PTE following TBI. This study suggests that improving the readability of health education materials may increase epilepsy-related health literacy, leading to more effective recruitment efforts for future clinical trials, as well as better patient-centered results. Learn More
  • New Treatment: Valtoco (diazepam), a nasal spray intended to treat seizure emergencies in patients 6 years of age and older, is now commercially available in the US. Learn More
  • Clinical Trial: Engage Therapeutics announced that its Phase 2b StATES study of Staccato® alprazolam, an orally inhaled therapy designed to terminate an active epileptic seizure, met its primary endpoint. This endpoint was a proportion of responders achieving cessation of seizure activity within two minutes of treatment administration and no recurrence within two hours. Learn More
  • Post-Traumatic Epilepsy: Research suggests that rats treated with certain drugs within a few days of a traumatic brain injury have a dramatically reduced risk of developing epilepsy later in life. Researchers found that suppressing an immune system receptor called Toll-like receptor 4 shortly after brain injury reduces seizure susceptibility and neuronal excitability in an important part of the brain called the hippocampus. Learn More
  • SCN8A Encephalopathy: A therapy that enables researchers to control gene expression in the brain, called antisense oligonucleotides (ASOs), has been utilized to stop seizures in a mouse model of SCN8A encephalopathy, a rare childhood epilepsy. By using ASOs, researchers delayed seizure activity and increased the lifespan of these mice. Learn More

The CURE Epilepsy Research Mobile App delivers research news to the palm of your hand! With frequent updates, you’ll always be in-the-know about the latest in epilepsy science. Download today. iOS | Android

Doctor wearing a white coat typing at a computer

Study Finds Need for Improved Readability of Online Health Education Materials to Improve Health Literacy Around TBI, Epilepsy and PTE

Objective: The use of the internet for health-related questions is increasing, but it is not clear whether individuals can understand the information available online. Most health organizations recommend that health educational materials (HEMs) be written below the sixth grade reading level. This study was designed to evaluate the readability level of available online HEMs pertaining to traumatic brain injury (TBI), epilepsy, and posttraumatic epilepsy (PTE).

Methods: This cross-sectional readability assessment included HEMs from TBI and epilepsy stakeholder organizations and those obtained from four internet searches. The search strategy was designed to replicate a nonmedical individual’s keyword searches. Each HEM was assessed with an online automated readability tool using three indices (Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Simple Measure of Gobbledygook). Findings were compared as a function of organization type (journalistic news or health organization), targeted medical condition (TBI, epilepsy, or PTE), or content topic (patient health education, clinical research education, or both).

Results: Readability analysis of 405 identified HEMs revealed scores above the sixth grade reading level recommendation. Only 6.2% of individual HEMs met the sixth grade recommendation. Journalistic news organizations’ HEMs had similar readability levels to health organizations’ HEMs. PTE-related HEMs required the highest readability level, >11th grade (P < .001). There were significant differences in the readability scores (P < .01 for all indices) among HEMs with information on health education, research education, or both topics. The highest required readability level (>12 grade level) was for HEMs that included both health and research education.

Significance: The majority of TBI-, epilepsy-, and PTE-related online health education materials do not meet the sixth grade reading recommendation. Improving the readability of health education materials may advance health literacy around TBI, epilepsy, and PTE, leading to more effective participant recruitment/retention strategies for future antiepileptogenesis trials in persons with TBI and perhaps better patient-centered outcomes.

Dr. Viji Santhakumar in her lab

Early Intervention Following Traumatic Brain Injury Reduces Epilepsy Risk

UC Riverside-led rat study finds an immune receptor in the hippocampus is responsible for the onset of the disease after brain injuries

A research team led by a scientist at the University of California, Riverside, has found that brain treated with certain drugs within a few days of an injury have a dramatically reduced risk of developing epilepsy later in life.

The development of epilepsy is a major clinical complication after brain injury, and the disease can often take years to appear.

“Working on rats, whose immune response system models that of humans, we identified that after brain injury a certain immune system receptor makes the brain more excitable, which promotes development of epilepsy,” said Viji Santhakumar, an associate professor of molecular, cell, and systems biology at UC Riverside and the lead author of the study that appears in the Annals of Neurobiology. “If this receptor can be suppressed, preferably within a day after injury, the future development of epilepsy can be reduced if not entirely prevented.”

The receptor in question is the Toll-like receptor 4, or TLR4, an innate immune receptor. Following a brain injury, TLR4 increases excitability in the dentate gyrus of the hippocampus, the brain structure that plays a major role in learning and memory.

“What our rat studies on traumatic brain injury show is that if we target early changes in excitability, we can alter long-term pathology,” Santhakumar said. “Blocking TLR4 signaling shortly after brain injury reduces neuronal excitability in the hippocampus and seizure susceptibility. This seizure susceptibility is not reduced if we delay the blocking of TLR4 signaling after injury.”

Paradoxically, Santhakumar’s team found that drugs such as Resatorvid, which block TLR4 in the injured brain, caused epilepsy in uninjured brains.

“This paradox is difficult to understand,” Santhakumar said. “We are currently looking at molecular signaling pathways in injured and uninjured brains to make sense of it.”

Epilepsy Research Findings: December 2019

This month, the FDA approved XCOPRI, a new medication to treat partial-onset seizures in adults. This type of seizure is often difficult to control, so we are thrilled to see this treatment advancement.

Additional promising research news includes the advancement of a method of predicting seizure risk. Also, for individuals affected by Lennox-Gastaut syndrome, a new Amazon Alexa skill offers engaging, interactive play options.

Summaries of these research discoveries and news highlights are below.

Research Discoveries & News

  • New Treatment: The FDA approved SK Lifescience’s XCOPRI (cenobamate tablets) to treat partial-onset seizures in adults. Learn More
  • Seizure Prediction: The new seizure risk assessment tool from Rice University, EpiSAT, received its first validation. The automated machine-learning algorithm correctly identified changes in seizure risk — improvement, worsening, or no change — in more than 87% of cases by analyzing seizure diaries. This prediction rate is as good or better than specialized epilepsy clinicians predicting seizure risk using patient histories. Learn More
  • New Technology: Eisai Inc. launched Ella the Jellyfish, the first Amazon Alexa skill designed for those affected by Lennox-Gastaut syndrome. This skill features capabilities such as interactive play, listening, and creative activities. Learn More
  • Status Epilepticus: New findings from a team, which included CURE Scientific Advisory Members Dr. Jaideep Kapur and Dr. Dan Lowenstein, reveal that levetiracetam (Keppra), fosphenytoin (Cerebyx), and valproate (Depakote) are equally safe and effective in treating patients with status epilepticus. Learn More
  • Post-Traumatic Epilepsy: Researchers from the University of California, Irvine (UCI) developed a cell therapy to improve memory and prevent seizures in mice following traumatic brain injury. In the study, the UCI team transplanted a cell type that can generate inhibitory brain activity into mouse brains. This process formed new connections with injured brain cells and prevented the mice from developing seizures. Learn More
  • Febrile Seizures: A study examined the cognitive functioning in children ages 4-5 who experienced febrile seizures. The research found that children with early onset of febrile seizures (especially those with recurrent febrile seizures) may be at heightened risk for poorer verbal and processing speed function, and possibly at risk for other cognitive dysfunctions. The findings suggest that these children would likely benefit from neuropediatric and neuropsychological follow-up, regardless of if they are still having febrile seizures. Learn More

Introducing the CURE Epilepsy Research Mobile App for research updates in the palm of your hand! Download today. iOS | Android

New Cell Therapy Improves Memory and Stops Seizures Following TBI

Researchers from the University of California, Irvine developed a breakthrough cell therapy to improve memory and prevent seizures in mice following traumatic brain injury. The study, titled “Transplanted interneurons improve memory precision after traumatic brain injury,” was published in Nature Communications.

Traumatic brain injuries affect 2 million Americans each year and cause cell death and inflammation in the brain. People who experience a head injury often suffer from lifelong memory loss and can develop epilepsy.

In the study, the UCI team transplanted embryonic progenitor cells capable of generating inhibitory interneurons, a specific type of nerve cell that controls the activity of brain circuits, into the brains of mice with traumatic brain injury. They targeted the hippocampus, a brain region responsible for learning and memory.

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after treatment, the mice showed signs of memory improvement, such as being able to tell the difference between a box where they had an unpleasant experience from one where they did not. They were able to do this just as well as mice that never had a brain injury. The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.