Study analyzes association of antiepileptic drugs and suicidality

According to a study, “A Temporal Evaluation of Antiepileptic Drugs and Suicidality: Is it the Medication or the Comorbidity?” [1]:

While individuals with antiepileptic drug exposure had higher likelihood of suicide related behavior, the trend started before the antiepileptic drug exposure and was not differentially associated with epilepsy status or antiepileptic drug type received.

[The study] compared trends of suicide related behavior before and after initiation of antiepileptic drug therapy among antiepileptic drug users with and without epilepsy to individuals without antiepileptic drug use controlling for sociodemographic characteristics and mental health comorbidity.

Given the limited information available on depression severity in this administrative data it is possible that the significant effect for antiepileptic drug exposure is due to residual confounding of mental health comorbidity.

Vagus nerve stimulator placement, corpus callostomy, or ketogenic diet initiation could help children with pharmacoresistent epilepsy

According to a study, “Seizure control and quality of life in children with epilepsy after vagus nerve stimulator placement, corpus callostomy, or ketogenic diet initiation” [1]:

Vagus nerve stimulator placement, corpus callostomy, and ketogenic diet was successful in reducing both generalized and focal seizure types, [with] ketogenic diet showing a trend towards slightly better success.

Parents of 210 patients, who had 292 (VNS, n=150; CC, n=44; KD, n=98) treatment modalities, agreed to participate in a phone interview. 60% were male with ages ranging from 8 months to 20 years. Seizure control, cognitive and behavioral factors, quality of life and treatment satisfaction was rated via a 9-item telephone questionnaire.

Improvements observed in cognitive and behavioral domains, better seizure control and less falls positively affected quality of life. Parent overall satisfaction was greater than 75%, which far outweighed seizure reduction or behavioral improvements.

These findings support palliative management for those with pharmacoresistant epilepsy who are not candidates for surgical resection.

CURE Taking Flight and Innovator Awards accepting applications

CURE is now accepting LOIs for its first 2018 grant cycle. These grants include:

  • Innovator Award – A grant of $50,000 paid over one year
  • Taking Flight Award – A grant of $100,000 paid over one year

 

The deadline for both of these grants is January 8, 2018 at 9pm Eastern.

Full Key Cycle 1 timeline details are below:

ActivityDate
Letter of Intent DeadlineMonday, January 8th, 2018 – 9pm ET
Full Application InvitationsWednesday, February 21st, 2018
Full Application DeadlineWednesday, March 28th, 2018 – 9pm ET
Anticipated Award AnnouncementJuly 2018
Anticipated Project Start DateSeptember 2018

 

For more information or to apply, interested parties should visit CURE’s Grant Opportunities webpage.

Balance and Anti-Epileptic Drugs Clinical Trial

Patients with epilepsy exercise less than the general population. A barrier to exercise may be the effect of antiepileptic drugs on balance and reaction time. This proposal endeavors to study the effect of two common antiepileptic drugs (levetiracetam and lamotrigine) on balance and reaction time using a Wii balance board and reaction time test. This will be tested at descending doses in an epilepsy monitoring unit. Drug levels will be monitored, as well as center of pressure, and reaction time.

Eligibility Criteria

Ages Eligible for Study: 16 Years to 55 Years (Child, Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes

Inclusion Criteria:

  • Focal or generalized epilepsy
  • On a stable dose of AEDs defined by no medication changes within the last month.
  • On levetiracetam or lamotrigine monotherapy

 

Exclusion Criteria:

  • Inability to stand independently for 30 seconds
  • Peripheral neuropathy
  • History of stroke or previous brain surgery
  • Seizure within last 24 hours

CURE and Lundbeck Announce 2017 Education Enrichment Fund Scholars

CHICAGO, IL – Citizens United for Research in Epilepsy (CURE) and Lundbeck have announced the naming of six new Education Enrichment Fund (EEF) Scholars.

The EEF Scholarships—made possible by generous support from Lundbeck—award a one-time scholarship (up to $5,000) to cover tuition, books, and course materials for those living with epilepsy, or for family members and caregivers of those impacted by the disease. The scholarship is to be used toward coursework advancing personal knowledge in research, health education, advocacy and/or awareness in relation to the recipient’s experiences with epilepsy.

Launched last year by CURE and Lundbeck with three scholars, the EEF Scholarship program has doubled in 2017 to fund six scholarships. The 2017 winners are:

  • Drake Abramson, University of Indianapolis
  • Jacqueline Bridges, University of Pittsburgh
  • Brianna Brodeur, University of Illinois—Champaign
  • Jordan Kaufman, Rollins College
  • Casey Nunes, Benedictine University
  • Nolan Wu, Trinity University

 

The 2017 scholars include students personally living with epilepsy and related syndromes, and ones caring for family members impacted by epilepsy. The scholars’ academic interests include neuroscience, biology, and public health—most with an eye to studying epilepsy.

“I am so inspired by the incredible individuals who have received the Education Enrichment Fund scholarships,” said Lorena Di Carlo, Vice President & General Manager, Neurology, at Lundbeck. “They have each taken adversity and channeled it into something positive. Lundbeck is honored to support them in their pursuit to help people who are living with epilepsy.”

“At CURE, we understand it’s vital to make a difference today in the lives of those impacted by epilepsy, and also to inspire and support the new generation of researchers and scholars that will hopefully end this disease,” said Kate Carr, CEO of CURE. “The EEF Scholars program helps us achieve both of these goals. Because of the strong support from Lundbeck, we are able to make a meaningful impact in the lives of these exciting young scholars.”

CURE Grantee Awards Announced

CURE is pleased to announce new recipients of funding for its Sleep & Epilepsy Award, Taking Flight Award, and Innovator Award grants. CURE presents these grants for novel research projects that focus on finding the cures for epilepsy and address the goal of “no seizures, no side-effects, end epilepsy” Specifically, CURE funds research that works to understand and prevent epilepsy, identify disease modifying or eliminating therapies, eliminate SUDEP (Sudden Unexpected Death in Epilepsy), and reverse deficits caused by frequent seizures. These researchers are added to the long list of distinguished CURE grantees helping pave the way to a cure for epilepsy. Since its inception in 1998, CURE has been at the forefront of epilepsy research, raising more than $50 million to fund over 200 cutting-edge projects in 15 countries around the world.

 

SLEEP & EPILEPSY AWARD GRANTEE

Franck Kalume, PhD
Seattle Children’s Hospital

Non-pharmacological manipulations of sleep and circadian rhythms to prevent seizures and sudden death in mouse models of refractory epilepsy

Acute and chronic sleep and circadian disruptions are commonly present in people with treatment-resistant epilepsies. They are linked to several negative consequences, including cognitive impairment, emotional disorders, and poor seizure control and quality of life. In planned studies, Dr. Kalume and his team will use well-established genetic mouse models of human refractory epilepsies, namely the Dravet syndrome and focal cortical dysplasia. First, they will correct sleep abnormality by manipulations of daily feeding, locomotor activity, or environmental temperature. Then, they will examine the impacts of these interventions on the course of epilepsy and sudden unexpected death phenotypes.

This award of $220,000 allows researchers to study the connection between sleep and epilepsy, and translate findings to significantly help patients. This Sleep and Epilepsy Award is possible because of support from The BAND Foundation.

 

TAKING FLIGHT AWARD GRANTEES

Gary Brennan, PhD
Royal College of Surgeons in Ireland

Towards the understanding of the epitranscriptome in epileptogenesis

The molecular mechanisms which drive the development of epilepsy following epilepsy-inciting events are still being unravelled. Once thought to merely represent the DNA code and facilitate translation, RNA has more recently been shown to be involved in numerous cellular and disease processes through the discovery of non-coding RNAs, regulatory long non-coding-RNA, circular RNAs, etc. Similarly, the regulation of RNA itself has been shown to be extremely complex. Analogous to DNA methylation and phosphorylation of proteins, RNAs have been shown to be subjected to complex regulation which determines their function. This work aims to characterise RNA regulation and function in pre-clinical mouse models of epilepsy and in human epileptic tissue, and understand how aberrant regulation of RNA can contribute to the development of epilepsy. It is hoped that gaining a more thorough understanding of the molecular drivers of epileptogenesis will allow the identification of novel anti-epileptogenic targets.

 

William Nobis, MD, PhD
Northwestern University

Evaluation of how extended amygdala control of the autonomic nervous system us altered in epilepsy and its implications for SUDEP

It has proven difficult to link the myriad proposed features leading to the cardiac and respiratory decline in sudden unexplained death in epilepsy (SUDEP). This project aims to identify a specific neuronal subtype in a deep brain nucleus which may be critical in cardiorespiratory control, providing a better understanding of the mechanism of SUDEP. The goal is first to identify that these neurons control cardiorespiratory functions and characterize them. Finally, we will verify that these neurons are activated in a genetic model of epilepsy in the hopes that further examination of these neurons might provide a potential therapeutic target to prevent SUDEP.

 

Flavia Vitale, PhD
University of Pennsylvania

A tunable, controllable microarray for mapping epileptic brain networks

Localization-related epilepsies account for the majority of patients with seizures, many of whom do not respond to medications. Surgery or treatment with implantable devices have the potential to make many patients seizure-free, but results are limited by our inability to precisely localize brain areas where seizures begin. Dr. Vitale has developed a new class of very small, flexible electrodes that can be independently controlled after they are implanted, allowing surgeons to safely map epileptic networks in the brain with high precision. With support from CURE, Dr. Vitale will build these new devices and test them in animal models of focal epilepsy, to detect and map seizure generation and spread. If successful, this exciting new technology could precisely localize seizure networks, and allow clinicians to focally ablate or suppress them with unprecedented accuracy, exactly where they are generated.

The Taking Flight Award of $100,000 seeks to promote the careers of young epilepsy investigators to allow them to develop a research focus independent of their mentor(s).

 

INNOVATOR AWARD GRANTEE

Tore Eid, MD, PhD
Yale University

Role of gut microbiota in epilepsy

Nearly one thousand different types of bacteria colonize the human gut.  Some of these bacteria are helpful to us, while others can cause disease.  Obesity, diabetes, stomach ulcers and Parkinson’s disease have all been linked to changes in the gut bacterial flora.  However, little is known about the role of the gut bacteria in epilepsy.  The goal in this research is to investigate whether certain types of gut bacteria can stop or trigger seizures and how they are able to do so.  If successful, our research could pave the way for completely new treatments for epilepsy by safely manipulating the gut bacteria using dietary intervention, probiotics, or short courses of antibiotics.

This $50,000 award explores a highly innovative new concept or untested theory that has the potential to reveal entirely new avenues for investigation in epilepsy research.

Positive airway pressure therapy improved seizure control in epileptic patients with obstructive sleep apnea

Sleep study, “1145 Long-Term Seizure Control in Epileptic Patients with Obstructive Sleep Apnea Using Positive Airway Pressure Therapy” found [1]:

[There were] better 1-year seizure outcomes in people with epilepsy and Positive Airway Pressure-treated Obstructive Sleep Apnea compared with Untreated Obstructive Sleep Apnea and No Obstructive Sleep Apnea.

[Researchers] investigated the effect of positive airway pressure therapy on long-term seizure outcomes in adults with epilepsy who underwent polysomnography at Cleveland Clinic (1997–2016). Seizure outcomes included mean % seizure reduction, ?50% seizure reduction from baseline (%, responder rate), and ? 50% seizure reduction or seizure free at both baseline and follow up (%, successful outcome).

Successful outcome was achieved more often in Positive Airway Pressure-treated (84%) than Untreated Obstructive Sleep Apnea (57%; p=0.002) or No Obstructive Sleep Apnea (66%; p=0.009) groups. [The results] expand existing literature supporting the impact of sleep therapies on seizure control in people with epilepsy.

Fenfluramine provides significant seizure reduction in Dravet syndrome, according to European Journal of Neurology study

The study “Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients” found [1]:

Patients with Dravet syndrome experienced sustained periods of clinically meaningful improved seizure control during fenfluramine treatment with a favorable tolerability and no echocardiographic or clinical evidence of cardiac valvulopathy or pulmonary hypertension.

Nine patients (aged 1.2–29.8 years) enrolled in the study and were treated with fenfluramine for a median duration of 1.5 (range, 0.3–5.1) years.

All patients demonstrated a reduction in seizure frequency during the treatment period with a median reduction of 75% (range, 28–100%). Seven patients (78%) experienced a ?50% reduction in major motor seizure frequency.

Epilepsy drug, Sodium Valproate, could cause medical problems trans-generationally, if taken by pregnant women

According to a Konkuk University study, “The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy,” conducted by researchers Chang Soon Choi et al.[1]:

The findings of this study present a new perspective in autism spectrum disorder susceptibility and heritability where autism can be inherited in subsequent generations after a pathologic environmental exposure in the first generation.

A well-known environmental risk factor of autism spectrum disorder in humans is the ValProic Acid, an anti-epileptic drug. ValProic Acid-exposed animals have become one of the most widely used models of autism spectrum disorder for its clinical relevance.

Autism-like behavioral phenotypes found in the first generation of ValProic Acid-exposed offspring persisted to the second generation and third generation. The frontal cortices of the first generation and third generation showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance.

These results open the idea that excitatory/inhibitory imbalance and autism spectrum disorder-like behavioral changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation.