Actual Experience with Direct Brain-Responsive Neurostimulation for Focal Onset Seizures

Abstract, published in Epilepsia

Objective: The RNS System® is a direct brain-responsive neurostimulation system that is approved by the US FDA for adults with drug-resistant seizures that begin in one area of the brain, based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real-world safety and effectiveness of the RNS System.

Results: One hundred fifty patients met the criteria for analysis. The average reduction in seizures was 67% at 1 year, 75% at 2 years, 82% at 3 years or more, and 74% at last follow-up (average = 2.3 years). Thirty-five percent of patients had a ?90% seizure frequency reduction, and 18% of patients reported being clinically seizure-free at last follow-up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, location of seizure onset, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9%; five of the six patients had an implant site infection, and one had a bone infection. Lead revisions were required in 2.7%, and 2.0% of patients had a subdural hemorrhage (a collection of blood outside the brain), none of which had long-lasting neurological consequences.

Significance: In this real-world experience, safety was similar and clinical seizure outcomes exceeded those of the prospective clinical trials, corroborating effectiveness of this therapy and suggesting that clinical experience has informed more effective programming of the RNS device.

Network Dysfunction in Coexisting Psychiatric Illnesses and Epilepsy

Abstract, published in Currents

The episodic nature of both epilepsy and psychiatric illnesses suggests that the brain switches between healthy and pathological states. The most obvious example of transitions between network states related to epilepsy are seizures, but there are more subtle changes in communication within and between brain regions, which these researchers propose may contribute to psychiatric illnesses associated with epilepsy.

This review will highlight evidence supporting abnormal network activity associated with epilepsy and the contribution to cognitive impairments and coexisting psychiatric illnesses. Further, it discusses potential mechanisms mediating the network dysfunction associated with coexisting disorders in epilepsy. Conceptually, it is necessary to think beyond seizure activity to appreciate the breadth of network dysfunction contributing to the spectrum of symptoms associated with epilepsy, including coexisting psychiatric illnesses.

Long-Term Employment, Education, and Healthcare Costs of Childhood and Adolescent Onset of Epilepsy

Abstract, published in Epilepsy and Behavior

Objective: Childhood- and adolescent-onset epilepsy may have a significant impact on long-term educational and vocational status, which in turn has consequences for individuals’ socioeconomic status. This research team estimated the factual long-term socioeconomic consequences and healthcare costs of individuals with diagnosed epilepsy.

Methods: The prospective cohort study included Danish individuals with epilepsy onset before the age of 18 years, diagnosed between 2002 and 2016. Healthcare costs and socioeconomic data were obtained from nationwide administrative and health registers. A total of 15,329 individuals were found with the diagnosis during this period and were followed until the age of 30 years. These were compared with 31,414 controls. The team used 30 years as this represent an age where most have completed their education, and as such, represent the final educational level. Individuals were matched for age, gender, and residential location.

Results: Compared with control groups, patients with epilepsy at the age of 30 years tended to have the following: 1) parents with lower educational attainment; 2) a significantly lower educational level when controlling for parental education attainment; 3) lower grade-point averages; 4) a lower probability of being employed and lower income; and 5) elevated healthcare costs, including those for psychiatric care. It was also noted that the long-term educational consequences for patients with epilepsy were associated with parental educational level. Differences were more pronounced for those with early (0-5 years) rather than later (6-18 years) onset epilepsy.

Conclusions: Epilepsy is associated with severe long-term socioeconomic consequences: lower educational level, school grades, employment status, and earned income. The presence of epilepsy seems to be associated with parental educational level.

One million Epilepsy Patients in China Missing Out on Beneficial Surgery

Press release, published by Monash University

In 2010, Professor Patrick Kwan from Monash University’s Department of Neuroscience, led an international team researching the causes and outcomes of epilepsy patients in rural China. A decade later the results indicate that at least one million Chinese people with epilepsy could be candidates for a standard operation that may leave them seizure-free.

The study, published in Neurology, incorporated 600 epilepsy patients from across four rural provinces in China from July 2010 and December 2012, with each participant undergoing an MRI and other tests looking for abnormalities in brain imaging. Of those, 108 were found to have lesions that could potentially be cured by surgery.

“In a best-case scenario, around 70-80% of them would be seizure-free – often after enduring seizures uncontrolled by medications for 20 years or more,” Professor Kwan said.

The participants were assessed by local primary care doctors trained by provincial neurologists in main hospitals to use a standardized questionnaire and take patient histories. The patients then traveled to provincial centers to have tests including MRIs and blood taken, for use in later research into genetic causes for epilepsy.

Professor Kwan said those patients identified as potential surgery candidates would need to undergo further tests including video-EEGs and neuropsychological assessments to ensure surgery would be effective, with the actual operation only taking three to four hours.

The same standard operation is carried out for suitable patients routinely around the world including Australia, UK and US.

“Extrapolating out the study results, potentially at least a million people could benefit from the operation – that’s a huge surgical treatment gap,” Professor Kwan said. “These findings are significant, highlighting the magnitude of the unmet needs for epilepsy surgery in China.

“Hopefully this information demonstrates a quantifiable need. By raising awareness we hope to influence policymakers to provide more resources in epilepsy care, including proper evaluation in specialist centers and proceeding to surgery if deemed appropriate.”

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The multicenter study was conducted with international collaborators in London, Shanghai and Beijing, and was funded by the National Institutes of Health (US) and Chinese Ministry of Science and Technology.

The statistical analysis in the study was conducted by Dr Zhibin (Ben) Chen (joint first author) from Monash University’s Department of Neuroscience. Also instrumental in the study were; joint first author Dr Indran Davagnanam, Dr Chandrashekar Hoskote, Professor John Duncan and Professor Josemir (Ley) Sander from UCL, Dr Wenzhi Wang from Beijing Neurosurgical Institute, and Associate Professor Ding Ding from Shanghai’s Fudan University.

Professor Kwan is a medical specialist in neurology, an internationally recognized expert in epileptology and antiepileptic drug development, and is the head of the Comprehensive Epilepsy Program at the Alfred Hospital in Melbourne.

For Media Enquiries please contact:

E: media@monash.edu
T: +61 (0) 425 725 836

Ways to Give

Fever-Associated Seizures After Vaccination Do Not Affect Development or Behavior

Press release from the American Academy of Neurology

A seizure associated with a fever is called a febrile seizure. Now a new study has found there is no difference in developmental and behavioral outcomes for children who have febrile seizures after vaccination, children who have febrile seizures not associated with vaccination and children who have never had a seizure. The new study is published in the July 1, 2020 online issue of Neurology®, the medical journal of the American Academy of Neurology. Febrile seizures are also known as febrile convulsions.

“This is reassuring news for parents,” said study author Lucy Deng, MBBS, of the National Centre for Immunisation Research and Surveillance (NCIRS) in Sydney, Australia. “A febrile seizure can occur following vaccination and understandably can be quite distressing to parents. It can also cause parents to lose confidence in future vaccinations. Now, parents will be relieved to hear that having a febrile seizure following vaccination does not affect the child’s development.”

The study compared 62 children who had a fever-associated seizure within two weeks after a vaccination with 70 children who had a fever-associated seizure from another cause and 90 children without a history of seizures. All of the children who had seizures were younger than 2-1/2 years old at the time of the seizure.

The children’s cognitive, motor and language functions were tested by certified developmental assessors who did not know the child’s seizure history. Their behavior was also assessed through questionnaires completed by their parents. The children with seizures were tested within one to two years after the seizure.

The researchers found no differences in development, thinking skills or behavior between the children who had febrile seizures following a vaccination and those who had febrile seizures at other times or those who never had a seizure.

“At a time when there is a global resurgence of measles and new diseases are emerging, our findings are particularly important in reassuring parents and providers on the safety of vaccines,” Deng said.

Deng also pointed out that several other factors were not associated with having developmental problems: fever-associated seizures before the age of one; a febrile seizure lasting for more than 15 minutes; or more fever-associated seizures after the first seizure.

Limitations of the study include a relatively small number of participants. Also, further studies should follow children for longer periods of time.

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The study was supported by the Australian National Health and Medical Research Council.

Learn more about febrile seizures at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.

When posting to social media channels about this research, we encourage you to use the hashtags #Neurology and #AANscience.

The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 36,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

For more information about the American Academy of Neurology, visit AAN.com or find us on Facebook, Twitter, Instagram, LinkedIn and YouTube.

Media Contacts:

Renee Tessman, rtessman@aan.com, (612) 928-6137
M.A. Rosko, mrosko@aan.com, (612) 928-6169

Seizure Pathways Change over Different Timescales in Individual Patients with Focal Epilepsy

Abstract, published in Proceedings of the National Academy of Sciences of the United States of America

Epilepsy is an episodic disease characterized by brief periods of abnormal brain activity, known as seizures, that often have clinical correlates. In many patients, seizures preferentially happen during certain stages of daily and multiday cycles. However, it is unclear whether and how seizures themselves change over time, even though such variability may have clinical implications.

To address this knowledge gap, this research team quantitatively analyzed the nature of within-patient variability in seizure networks using intracranial electroencephalographic (iEEG) recordings of over 500 seizures from 31 patients with focal epilepsy (average of 16.5 seizures per patient). An iEEG is a type of EEG in which electrodes are placed directly on the brain, and a focal seizure is one in which the seizures starts from a single location in the brain.

Contrary to common expectations, this study found seizure variability throughout our group of patients. Importantly, the team demonstrated that seizures do not change randomly; instead, they also appear to fluctuate over daily and slower timescales. These results suggest that various modulatory processes, operating at different timescales, appear to lead to variable seizure pathways in individual patients. Ultimately, we may improve treatments by tailoring interventions to the full range of seizures in each patient.

International Study Uncovers Three Molecules with Potential for Treating Epilepsy

Featuring the work of former CURE Grantee Dr. David Henshall

Summary, published by the Royal College of Surgeons in Ireland

The findings are an important step towards discovering new drugs for people with epilepsy whose seizures cannot be controlled with current treatments.

The study was led by researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases and RCSI University of Medicine and Health Sciences. It is the result of seven years of research, involving contributions from 35 scientists, based in eight different European countries, across the fields of neuroscience, genetics, computer science and synthetic chemistry. The research is published in the current issue of Proceedings of the National Academy of Sciences (PNAS).

In one of the largest sequencing projects of its kind, researchers identified and measured levels of over a billion strands of microRNAs – small molecules that control gene activity in the brain – to investigate if they were changed in epilepsy. They discovered a small set of microRNAs which were always elevated in epilepsy and designed drug-like molecules, synthesized by chemists from the group, to target these. Three of the synthetic molecules were found to stop seizures in preclinical tests.

Computer simulations demonstrated how the potential treatments influenced molecule networks inside brain cells by changing the inflammatory response, part of the brain’s immune system which is thought to contribute to seizures.

“Our approach to drug discovery has led us to new types of molecules that can be targeted to prevent seizures with hopefully fewer side effects,” said Dr Cristina Reschke, FutureNeuro Research Fellow and Honorary Lecturer at RCSI, and Co-Lead Author. “Currently, most drugs used to treat epilepsy work by blocking the signals brain cells use to communicate. This results in many of the side effects experienced by people with epilepsy.”

Which Seizure Elements Do Patients Remember? A Comparison of History and Seizure Documentation

Abstract, published in Epilepsia

Objective: People with epilepsy (PWE) are frequently unable to recall the core manifestation of their disease, epileptic seizures. This means that seizure frequency is often underestimated by practitioners and that seizure classification based on reports of patients or their relatives is difficult because seizure symptoms remain unclear. The purpose of this study, therefore, was to prospectively explore patients’ memory regarding seizure elements and to assess the role of seizure types.

Methods: Ninety patients diagnosed with focal epilepsy undergoing diagnostic electroencephalography (EEG)–video monitoring were included. The ability to remember individual seizure elements was assessed using a questionnaire. Patient memory was then compared to the findings of subsequent seizure documentation during EEG?video monitoring. Seizure elements were categorized in four groups: subjective, motor, autonomic, and postictal (immediately after the seizure) elements.

Results: In all categories, the number of documented seizure elements during monitoring strongly exceeded the number of elements that were recalled. Only 45.6% of subjective elements, 5.4% of motor phenomena, 11.9% of autonomic findings, and 2.1% of postictal impairments were recalled. The ability to recall seizure elements varied significantly depending on seizure types (secondarily generalized tonic?clonic seizures [SGTCS] < complex partial seizures [CPS] < simple partial seizures [SPS]), but not on the relative timing of the element during the seizure.

Significance: Patients’ memory of seizure symptoms is almost always fragmentary. Although the rate of correctly remembered seizure elements depends on the seizure type, complete recall of a seizure is almost never obtained. Consequently, 89 of 90 patients in this cohort would only have had seizures classified as a seizure with “impaired awareness,” according to the new International League Against Epilepsy (ILAE) seizure classification.

Daily listening to Mozart Reduces Seizures in Individuals with Epilepsy: A Randomized Control Study

Abstract, published in Epilepsia Open

Objective: Epilepsy is one of the most common neurological disorders. Many individuals continue to have seizures despite medical and surgical treatments, suggesting adjunctive management strategies are required. Promising effects of daily listening to Mozart on reducing seizure frequency in individuals with epilepsy have been demonstrated over the last 20 years, but not in a rigorously controlled manner. In this study, researchers compared the effect on seizure frequency of daily listening to either Mozart K.448 (a specific piano concerto written by Mozart) or a spectrally similar, yet non-rhythmic control piece. They hypothesized that there would be no difference in seizure counts when participants listened to Mozart K.448 vs when they listened to the control piece.

Methods: The research team employed a randomized crossover design, in which each participant was exposed to both three months of daily listening to the first six minutes of Mozart K.448 (treatment period) and three months of daily listening to phase-scrambled version (control period). There was a three-month baseline and a three-month follow-up period before and after the six-month listening period, respectively. Change in seizure counts obtained from the seizure diaries was considered as the main study outcome.

Results: Analysis revealed a reduction in seizure counts during the treatment period, which was not observed for the control period.

Significance: Using a spectrally similar control piece, this study advances previous reports that were limited by a “no music” control condition. Daily listening to Mozart K.448 was associated with reducing seizure frequency in adult individuals with epilepsy. These results suggest that daily Mozart listening may be considered as an adjunctive therapeutic option to reduce seizure burden in individuals with epilepsy.

Researcher Update: June 2020

In this month’s researcher update you will find information on:

Catalyst Award LOIs Monday, July 6

Request for Proposals (PDF)

The deadline is approaching to apply for CURE’s newest grant mechanism, the Catalyst Award. This award (2 years / $250,000) aims to stimulate and accelerate the discovery and development of new therapies for epilepsy, moving promising, well-supported preclinical and/or clinical research closer to clinical application.

  • Open call for Letters of Intent: Monday, June 1, 2020
  • Letter of Intent deadline: Monday, July 6, 2020, 9 PM ET
  • Full proposal invitations: Thursday, August 13, 2020
  • Full proposal deadline: Thursday, September 17, 2020, 9 PM ET
  • Awardee notification: Late-December 2020
  • Anticipated award start date: March 2021

Epilepsy & COVID-19 Survey for Healthcare Providers

Take Survey

SUDEP Action and the Oxford Epilepsy Research Group are collaborating to better understand what risks people with epilepsy and healthcare providers are facing, what support they have and how to help them live well with the condition. Particularly during the current COVID-19 pandemic, it is important to explore the changes and challenges healthcare providers and patients are facing so they can be better supported.

NINDS Career Opportunities

NINDS has positions available for Health Scientist Administrators in the Epilepsy Therapy Screening Program and the Preclinical Screening Platform for Pain. Please don’t hesitate to send this update along to anyone you think may be interested in applying!

Submit an Abstract to the PAME Conference by June 29!

Submit Abstract

The PAME Conference, which is happening December 3-4 in conjunction with AES, has extended the deadline to submit abstracts to June 29. This conference aims to improve our understanding of mortality in epilepsy, including Sudden Unexpected Death in Epilepsy (SUDEP), by bringing together health care providers, researchers, public health officials, patient advocates, caregivers, bereaved families, and patients living with epilepsy. Abstracts should be submitted through the AES portal.

NIH Request for Information: Developing an Online Educational Resource for Training in the Principles of Rigorous Research

Submit Comment

NINDS is requesting your input to better provide accessible education on the principles of rigorous biomedical research for members of the scientific community. In particular, NINDS encourages experts in training, rigorous experimental design and implementation, mentoring, education, and technology to contribute their input.

AES Offering CE and CME Credit for 2019 Sessions

View Sessions

AES is now offering CE and CME credit for 2019 AES recorded sessions. The goal of these online materials is to provide knowledge and training for professionals working the epilepsy field and provide clinicians with resources to help improve the care of those with epilepsy.