News Topics: SUDEP

Epilepsy Research Findings: June 2019

This month’s round-up of epilepsy news features an announcement about a new antiepileptic rescue medication, NAYZILAM®. This therapy is the first FDA-approved nasal treatment option for people with epilepsy who experience episodes of frequent seizure activity.

We also highlight many research advances, from the discovery of a compound found in fruit and honey which can inhibit seizures to the development of a new drug to treat Dravet syndrome. Research in the cannabidiol (CBD) space has also advanced, with the creation of a synthetic form of CBD which may be easier to purify and does not need to be cultivated from hemp plants.

In more sobering news, reports over the past month show that one-third of epilepsy cases go without appropriate treatment for up to three years following diagnosis. In addition, people with psychogenic nonepileptic seizures (PNES) as well as epileptic seizures may be at a higher risk for sudden unexpected death in epilepsy (SUDEP)during the years immediately following diagnosis with PNES.

Summaries of all highlighted studies follow below. I’ve organized the findings into three categories: Treatment Advances, Research Discoveries, and Also Notable.

Treatment Advances

FDA Approves NAYZILAM® Nasal Spray to Treat Intermittent, Stereotypic Episodes of Frequent Seizure Activity in People Living with Epilepsy in the US
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The FDA has approved a New Drug Application for UCB’s newest antiepileptic drug NAYZILAM® (midazolam) nasal spray. This therapy is a benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) distinct from a patient’s usual seizure pattern in individuals with epilepsy who are 12 years of age and older.

Study Advances More Effective Laser Ablation and Standard Epilepsy Surgery 
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In the largest study of its kind to date, researchers across 11 centers analyzed data on a relatively new minimally invasive alternative surgery for epilepsy. These researchers discovered changes that could make the procedure more effective in both laser ablation and standard surgery.

Research Discoveries

Brain Network Activity can Improve in Epilepsy Patients after Surgery
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Successful epilepsy surgery can improve brain connectivity similar to patterns seen in people without epilepsy, according to a new study published in the journal Neurosurgery. The study of 15 people with temporal lobe epilepsy is the first to show improvements in brain networks after surgery compared to a group of healthy subjects.

New Drug Could Help Treat Neonatal Seizures
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A new drug that inhibits neonatal seizures in rodent models could open new avenues for epilepsy treatment in human newborns. Researchers have found that gluconate—a small organic compound found in fruit and honey—acts as an anticonvulsant, inhibiting seizures by targeting the activity of channels that control the flow of chloride ions in and out of neonatal neurons.

Research Looks to Halt Stress-Induced Seizures Following Brain Injury
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The likelihood of developing epilepsy increases significantly with a traumatic brain injury. Stress and anxiety increase that likelihood even more dramatically. Researchers have been able to demonstrate that an injured brain responds differently to stress hormones than a healthy brain. The research team showed abnormal electrical activity in the brain tied to these stress-induced seizures and, most importantly, found a way to stop this activity from occurring.

Synthetic Version of Cannabidiol (CBD) Treats Seizures in Rats
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A synthetic, non-intoxicating analogue of CBD was found to be effective for treating seizures in rats. Researchers note the synthetic CBD alternative is easier to purify than a plant extract, eliminates the need to use agricultural land for hemp cultivation, and could avoid legal complications associated with cannabis-related products.

AZD7325 Has Seizure-Protective Effect in Mouse Model of Dravet Syndrome, Study Says
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Treatment with AZD7325, a compound that stimulates an inhibitory receptor in the brain, has a seizure-protective effect in a mouse model of Dravet syndrome. This treatment significantly increased the temperature threshold animals could withstand without experiencing any seizures during a hyperthermia-induced seizure test.

Children’s Brains Reorganize after Epilepsy Surgery to Retain Visual Perception
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Children can keep their full ability to process and understand visual information after brain surgery for severe epilepsy, according to a study funded by the National Eye Institute, part of the National Institutes of Health. This new report from a study of children who underwent epilepsy surgery and suggests that the lasting effects on visual perception can be minimal, even among children who lost tissue in the brain’s visual centers.

One-Third of Epilepsy Cases Go Untreated up to 3 Years After Diagnosis
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A small yet substantial subset of patients with newly diagnosed epilepsy go without appropriate treatment approximately 3 years after diagnosis. This gap in treatment may be increasing the risk for medical events and hospitalization in these patients.

Study Suggests ‘High Risk Period’ for SUDEP for People with Psychogenic Nonepileptic Seizures in Addition to Epileptic Seizures 
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Findings of a recently published study suggest that patients with comorbid epileptic seizures (ES) and Psychogenic Nonepileptic Seizures (PNES) can die from SUDEP and that there may be a high?risk period after the diagnosis of PNES is made. The authors state such patients should be closely monitored and provided with coordinated care of both their epilepsy and psychiatric disorder(s).

Also Notable

Fralin Biomedical Research Institute Neuroscientist Awarded Grant to Study Epilepsy
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Featuring CURE Grantee Dr. Sharon Swanger

Dr. Sharon Swanger of the Fralin Biomedical Research Institute was recently awarded a $1.7 million grant through the National Institute of Neurological Disorders and Stroke to study the role of glutamate receptors in the thalamus – an area of the brain involved in seizure generation. “If we can figure out how each [receptor] subtype functions and modulate select subtypes, then maybe we can target therapies to the circuit where the disease originated while leaving healthy circuits intact,” said Dr. Swanger.

Tool Helps GPs Predict Risk of Seizures in Pregnancy
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Doctors, midwives, and others can use a new risk calculator to identify those pregnant women at high-risk of seizures and to plan early referral for specialist input. The specialist could determine the need for close monitoring in pregnancy, labor, and after birth, and assess antiepileptic drug management, according to new research in PLOS Medicine. The study authors added that the model’s performance is unlikely to vary with the antiepilepsy drug dose management strategy – and that it could save maternal and infant lives.

Development of Epilepsy Prediction Device to Improve Independence for People with Epilepsy
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The University of Sydney’s Faculty of Engineering and Information Technologies is developing a system, NeuroSyd, which aims at real-time monitoring and processing of brain-signals while driving in a group of people living with epilepsy. NeuroSyd will be developed to deliver an early warning of the likelihood of an epileptic seizure.

Pfizer’s Lyrica at Doses 5mg and 10mg Fails Phase 3 Trial in Epilepsy
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Pfizer’s Lyrica has failed to meet its primary endpoint in a phase 3 trial in primary generalized tonic-clonic (PGTC) seizures. The study evaluated two doses of the drug – 5 mg and 10 mg – over a period of 12 weeks. Treatment with the drug did not result in a statistically significant reduction in seizure frequency versus placebo. Another phase 3 trial in May 2018 was successful, showing that a 14 mg dose of Lyrica resulted in a statistically significant reduction in seizure frequency versus placebo.

Study Suggests ‘High Risk Period’ for SUDEP for People with Psychogenic Nonepileptic Seizures in Addition to Epileptic Seizures

Background: This study reports 13 SUDEP cases in the North American SUDEP Registry with both psychogenic nonepileptic (PNES) and epileptic (ES) seizures among a consecutive series of 231 cases (excluding epileptic encephalopathies).

Results: On average, cases of PNES+ES died at a younger age (23 ± 11 years) than the ES-only cohort (30 ± 14 years), and died an average of 3 years after PNES diagnosis. The research team found no statistically significant confounding cardiac, respiratory, or psychiatric comorbidities and equal rates of anti-seizure medication adherence, although there was a trend for higher rates of psychiatric disorders in the PNES group.

Significance: Researchers state these findings confirm that patients with comorbid epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) can die from SUDEP and that there may be a high-risk period after the diagnosis of PNES is made in patents with comorbid ES. Such patients should be closely monitored and provided with coordinated care of both their epilepsy and psychiatric disorder(s).

Study Explores Way to Automate Detection of Sudden Unexpected Death in Epilepsy Risk Factors in Electronic Medical Records

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. However, there is a gap in how often providers counsel patients about SUDEP. One potential solution is to electronically prompt clinicians to provide counseling via automated detection of risk factors in electronic medical records (EMRs). This study evaluated (1) the feasibility and generalizability of using regular expressions to identify risk factors in EMRs and (2) barriers to generalizability.

METHODS: Data included physician notes for 3000 patients from one medical center (home) and 1000 from five additional centers (away). Through chart review, the researchers identified three SUDEP risk factors: (1) generalized tonic-clonic seizures, (2) refractory epilepsy, and (3) epilepsy surgery candidacy. Regular expressions of risk factors were manually created with home training data, and performance was evaluated with home test and away test data. Performance was evaluated by sensitivity, positive predictive value, and F-measure. Generalizability was defined as an absolute decrease in performance by <0.10 for away versus home test data. To evaluate underlying barriers to generalizability, the team identified causes of errors seen more often in away data than home data. To demonstrate how small revisions can improve generalizability, researchers removed three “boilerplate” standard text phrases from away notes and repeated performance.

RESULTS: Researchers observed high performance in home test data (F-measure range = 0.86-0.90), and low to high performance in away test data (F-measure range = 0.53-0.81). After removing three boilerplate phrases, away performance improved (F-measure range = 0.79-0.89) and generalizability was achieved for nearly all measures. The only significant barrier to generalizability was use of boilerplate phrases, causing 104 of 171 errors (61%) in away data.

SIGNIFICANCE: Regular expressions are a feasible and probably a generalizable method to identify variables related to SUDEP risk. This study’s methods may be implemented to create large patient cohorts for research and to generate electronic prompts for SUDEP counseling.

SUDEP Action Win BMJ Award for Life-Saving Epilepsy Tools

SUDEP Action claimed Education Team of the Year at the British Medical Journal (BMJ) Awards 2019.

Judges commented that the ‘outstanding winner’ of the category were two free lifesaving epilepsy safety tools; the digital app EpSMon for people with epilepsy, and the clinician tool, the SUDEP and Seizure Safety Checklist.

The charity is working on bringing the lifesaving solutions, which it says transforms epilepsy patient safety, to wider Oxfordshire and across the UK.

Sammy Ashby, SUDEP Action Deputy CEO and manager ofthe projects, said: “We’re delighted that these projects have been recognized by this award; many people with epilepsy and their clinicians are not well supported to reduce their risks, yet these simple conversations and checks have the potential to save many lives each year.”

Are Febrile Seizures Associated With Increased Sudden Death Risk in Young Children?

Children with febrile seizures (FS) have a small yet elevated risk for death. Recent data suggest that FS may contribute to sudden unexplained death in childhood (SUDC) among cases of sudden explained death in childhood (SEDC). This is according to findings published in JAMA Network Open from one of the largest studies of its kind exploring the role of FS and other risk factors in SUDC.

A total of 622 consecutive cases of sudden child death that occurred from 2001 to 2017 were included in the review. Data were collected from voluntary records of family members who were registered with the SUDC Foundation. The final cause of death resulted in cases categorized as either SEDC or SUDC. The main outcome measure included the certified manner of death as accident, natural, or undetermined.

Ketogenic Diet May Reduce Sudden Unexpected Deaths in Epilepsy, Mouse Study Suggests

Sudden Unexpected Death in Epilepsy (SUDEP) occurs more frequently during early evening and is significantly prevented by prolonged use of the ketogenic diet, research in a mouse model of Dravet syndrome (DS) suggests.

The reasons why this happens are unclear, and should be examined in more depth by future studies, but these findings may be useful to understand why most SUDEP episodes happen at night and how certain diets can benefit epileptics, especially those with Dravet syndrome, researchers say.

Their study, “Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1aR1407X/+ Mice,” was published in the journal Frontiers in Neurology.

Using an established mouse model of Dravet syndrome, the researchers investigated if the time of the day influences the chances of sudden death. They also sought to determine if a ketogenic diet — a high-fat, low-carbohydrate (low-sugar) diet which helps to control seizures in some epileptic patients — can change the frequency of seizures and the rate of mortality.

Mice were continuously recorded on video to monitor for spontaneous seizures and sudden deaths. The recordings showed that SUDEP and spontaneous seizures happened more often during the early evening.

CURE Discovery: Safe, Quick Measurement in Epilepsy Monitoring Units (EMUs) Has Potential To Identify SUDEP Risk

When the body detects high carbon dioxide (CO2) levels in the blood, a condition known as hypercapnia, it responds by moving more air through the lungs. This increased ventilation helps remove the excess CO2. Research by CURE grantee Dr. Rup K. Sainju and his team at the University of Iowa shows that this response may be weakened in some people with drug-resistant epilepsy, which puts them at an increased risk for severe breathing abnormalities and Sudden Unexpected Death in Epilepsy (SUDEP) following a generalized convulsive seizure.

For their CURE-funded project, Dr. Sainju’s team conducted a study in adults with drug-resistant epilepsy who were admitted to the epilepsy monitoring unit (EMU) at the University of Iowa. In addition to comprehensive heart and breathing monitoring, the team measured the hypercapnic ventilatory response (HCVR) in each patient.1,2 The HCVR measurement evaluates how the body responds to increased blood CO2levels. A low HCVR indicates a poor or weakened ability to remove CO2 from the body.

Epilepsy Monitoring Unit

The study found that patients who had a low HCVR were more likely to have severe breathing abnormalities and a longer period of high, potentially dangerous CO2 levels in the blood after a generalized convulsive seizure. Long-term follow-up revealed one of the patients in the study with the third lowest HCVR passed away of SUDEP 11 months after the study.2

Importantly, this is the first time HCVR has ever been studied in patients with epilepsy. The team demonstrated that an HCVR measurement can be conducted in the EMU rapidly and safely.2 The team also reported that the HCVR measurement was well tolerated by the patients.2

Building on their work, Dr. Sainju’s team also conducted a CURE-funded pilot study to determine if the drug fluoxetine, more commonly known as Prozac, could increase HCVR and reduce seizure-related breathing abnormalities. Fluoxetine increases the availability of serotonin in the brain and there is evidence that the serotonin system increases ventilation in response to hypercapnia. Drugs similar to fluoxetine have been safely tested in mice and humans and shown to increase HCVR. The team hypothesized that giving fluoxetine to patients who have a low HCVR would improve the body’s ability to sense high CO2 levels and reduce post-seizure breathing abnormalities. The team has finished this study, which shows that patients completed it with good adherence. We are eager to see their final analysis.

Dr. Sainju’s study suggests that HCVR is a key measurement which may be useful in predicting the risk of breathing abnormalities and SUDEP. It can be easily and rapidly performed in the EMU with minimal discomfort to people with epilepsy. Future studies will build on this work, analyzing the usefulness of HCVR as a biomarker for SUDEP. Having demonstrated the feasibility of a randomized trial of fluoxetine versus placebo to improve HCVR, the team plans to continue studying fluoxetine and other therapeutic targets.

1 Gehlbach BK et. al. Tolerability of a comprehensive cardiorespiratory monitoring protocol in an epilepsy monitoring unit. Epilepsy Behav. 2018 Aug;85:173-176.
2 Sainju R.K. et. al. Ventilatory response to CO2 in patients with epilepsy. Epilepsia. 2019 Mar;60(3):508-517.
3 Hodges MR, Richerson GB. Medullary serotonin neurons and their roles in central respiratory chemoreception. Respir Physiol Neurobiol. 2010 Oct 31;173(3):256-63.

Epilepsy Research Findings: April 2019

This month’s news features technological advances that may make seizure detection more reliable and surgery for intractable epilepsy more accurate, while also deepening our understanding of how epilepsy arises in a healthy brain.

In other news, important research on Sudden Unexpected Death in Epilepsy (SUDEP) highlighted the association between SUDEP and change in tissue volume in areas of the brain important in cardiorespiratory function, as well as the lack of understanding about SUDEP among people with epilepsy and their relations.

In addition, we spotlight a recent statement by the FDA reporting that some people, mainly youth and young adults, who use e-cigarettes are experiencing seizures, as well as a recent TEDx Talk about how artificial intelligence may be used to help prevent SUDEP.

Summaries of all highlighted studies follow below. I’ve organized the findings into four categories: Treatment Advances, Diagnostic Advances, Research Discoveries, and Also Notable.

Treatment Advances

First Clinical Trial of Reformulated Antiepileptic Drug to Treat Medically Refractory Epilepsy
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An approved antiepileptic drug used to treat seizures has been modified and is currently being used in an Australian clinical trial for medically refractory epilepsy. The trial tests a proprietary, reformulated, specialty pharmaceutical, which bypasses the blood-brain barrier using a chronic implantable infusion system.

Multicenter Clinical Study of Long-Term Brivaracetam Use Finds It Effective and Well-Tolerated in Patients with Drug-Resistant Epilepsy
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Researchers assessed long-term effectiveness and tolerability of brivaracetam in patients with focal epilepsy. According to this multicenter, retrospective study, brivaracetam was effective and well-tolerated in a large population of patients with predominantly drug-resistant epilepsy. There were no unexpected adverse side effects over 1 year. The most frequently reported adverse side effects were somnolence, irritability, and dizziness.

Diagnostic Advances

Motion Recognition Technology Assists Epilepsy Diagnosis
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Motion recognition technology is being used to help neurologists study patients’ behavior during seizures. They hope to get clues on the sub-type of epilepsy the patient has and identify unusual seizure movements requiring further investigation.

Model Developed to Help Identify Patients Who Will Not Experience Remission Again After Breakthrough Seizures
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A model has been created to help identify people with epilepsy who are unlikely to regain seizure remission within 2 years after experiencing a breakthrough seizure following an initial 12-month remission. Researchers note that their model is a useful first step in developing a tool for identifying patients who develop drug resistance after an initial remission.

Research Discoveries

Potential Biomarkers of Cardiac Stress After Generalized Convulsive Seizures Identified
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The measurement of certain substances in the blood, such as the protein high-sensitive troponin T and the peptide copeptin, may be helpful as biomarkers to identify cardiac stress after generalized convulsive seizures in patients with refractory epilepsy, according to study results published in Epilepsia.

SUDEP Associated with Tissue Volume Change in Brain Areas Important in Cardiorespiratory Recovery
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In a retrospective imaging study of SUDEP cases, researchers found that people who passed away due to SUDEP show significant tissue loss in areas of the brain essential for cardiorespiratory recovery. They also found enhanced volumes in areas that trigger hypotension or impede respiratory patterning. According to the study, these changes in brain tissue may shed light on the mechanisms of SUDEP and help detect patterns to identify those at risk for SUDEP.

Literature Review Shows That There is a Lack of Understanding of SUDEP for People with Epilepsy and Their Relations
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A comprehensive electronic search of peer-reviewed qualitative studies showed an overall lack of understanding about unexpected epilepsy-related death among people with epilepsy and their relations. The authors conclude that it would be appropriate and necessary to discuss SUDEP with patients and their family members upon diagnosis.

Also Notable

Some E-cigarette Users Are Having Seizures; Most Reports Involving Youth and Young Adults
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The FDA has become aware that some people who use e-cigarettes have experienced seizures, with most reports involving youth or young adult users. A recent uptick in voluntary reports of adverse events with tobacco products that mentioned seizures occurring with e-cigarette use (e.g., vaping) signal a potential emerging safety issue, according to the FDA.

New TEDx Talk Issues Call to Action for SUDEP
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Every year worldwide, more than 50,000 otherwise healthy people with epilepsy suddenly die — a condition known as SUDEP. These deaths may be largely preventable, says artificial intelligence researcher Rosalind Picard. Learn how Picard helped develop a cutting-edge smartwatch that can detect epileptic seizures before they occur and alert nearby loved ones in time to help.

Laser Light Examines How Epilepsy Arises in the Healthy Brain
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Scientists have developed a new method to study how seizures arise in healthy brains. Using laser light guided through ultra-thin optic fibers in rodent brains, the researchers “turned on” light-sensitive proteins in selective brain cells and were able to eventually cause seizures through repeated laser stimulation.

Developing a Universal Automated Tool for Reliable Seizure Detection in Rodent Models of Acquired and Genetic Epilepsy
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The development of an automated tool for reliable seizure detection has the potential to improve the efficiency and rigor of preclinical research and therapy development for rodent models of acquired and genetic epilepsy, according to research published in Epilepsia.

Robotics Makes Intractable Epilepsy Surgery More Accurate
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Patients with intractable epilepsy who had a minimally invasive surgery evaluation procedure called robotic stereoelectroencephalography (SEEG) experienced fewer complications, according to a study published in JAMA Neurology. Those who went on to have brain surgery were more likely to be seizure-free than patients who had the more invasive evaluation procedure.

New TEDx Talk Issues Call to Action for SUDEP

Every year worldwide, more than 50,000 otherwise healthy people with epilepsy suddenly die — a condition known as SUDEP. These deaths may be largely preventable, says AI researcher Rosalind Picard. Learn how Picard helped develop a cutting-edge smartwatch that can detect epileptic seizures before they occur and alert nearby loved ones in time to help.

This talk was presented to a local audience at TEDxBeaconStreet, an independent event. TED’s editors chose to feature it for you.

CURE Discovery: Using Patient-Specific Cardiac Cells to Predict SUDEP Risk

CURE-funded researchers are using a novel technique to discover ways to predict patients at an increased risk of Sudden Unexpected Death in Epilepsy (SUDEP). Dr. Lori Isom, her team, and co-investigator Dr. Jack Parent at the University of Michigan are transforming skin cells from patients with developmental and epileptic encephalopathy (DEE) syndromes into induced pluripotent stem cells (iPSCs). The team then generates cardiac cells from the iPSCs which retain the patients’ exact genetic information. These unique, patient-specific cardiac cells are used as models to understand if DEE-associated genes play a role in causing heart abnormalities which may lead to SUDEP. The team also hopes to develop measurable indicators, known as biomarkers, of SUDEP risk.

Severe DEE syndromes, such as Dravet syndrome, are associated with a high incidence of SUDEP. It is estimated that up to 20% of patients with Dravet syndrome die from SUDEP.1 There is still much to be understood about the mechanisms of SUDEP and how to predict who is at risk for it.

Dravet syndrome and other DEEs are often associated with variants in genes, such as SCN1A, SCN1B, and SCN8A. These genes provide instructions to make sodium ion channels, which are very important proteins that help brain cells transmit electrical signals. The same genes are also expressed in the heart; thus, the team hypothesizes that any variants in these genes that disrupt electrical signaling in the brain would affect normal electrical function of the heart as well. In support of this hypothesis, the investigators’ previous work in mouse models of Dravet syndrome and DEEs showed that these mice exhibited irregular heartbeat, which in some cases preceded SUDEP-like events.2-4

In this CURE-funded project, the investigators expanded upon their previous work by testing their hypothesis in heart muscle cells called cardiac myocytes, generated in the laboratory from skin cells of patients with Dravet syndrome or other DEEs using iPSC technology. This Nobel Prize-winning technology involves obtaining skin or blood cells from patients and converting them to iPSCs. These are stem cells that can be converted into almost any specialized cell type in the body, such as heart, muscle, pancreatic, or neuronal cells. The cells are patient-specific, meaning they retain the unique genetic make-up of the patient they originated from, allowing investigators to study cell types which would otherwise be very difficult or impossible to obtain from a living patient.

Dr. Isom, Dr. Parent, and their colleagues previously used iPSC technology to generate heart muscle cells from four patients with variants in the SCN1A gene and found increased sodium currents and spontaneous contraction rates in these cells, suggesting cardiac electrical dysfunction.5 Cardiac abnormalities were subsequently found in the patient with the highest increase in sodium current.5 These data suggest that iPSC-cardiac cells may be useful models for identifying and developing biomarkers, such as increased sodium current, as indicators of SUDEP risk.

The investigators used the same technique to study variants in the SCN1B and SCN8A genes. The team observed that iPSC-cardiac myocytes derived from a patient with SCN1B Dravet syndrome had increased sodium currents similar to those seen in iPSC-cardiac myocytes from the patient with SCN1A Dravet syndrome, suggesting that variants in these two different genes could cause heart abnormalities through similar mechanisms. Preliminary data in iPSC-cardiac myocytes from patients with DEE caused by variants in SCN8A, suggest that these cells have altered beating rates but no change in sodium current, which is aligned with their observations in a mouse model with a variant in SCN8A.

Taken together, these results reveal mechanisms by which different epilepsy-related genes can affect heart function and SUDEP. Future research will investigate the impact of variants of a specific non-ion channel gene to see if it causes altered cardiac beating. Patient-specific iPSC cardiac myocytes are a very useful model to study SUDEP mechanisms and could be developed as diagnostic biomarkers to identify SUDEP risk in patients.

1 Cooper MS et al. Mortality in Dravet Syndrome. Epilepsy Res. 2016 Dec; 128:43-47.
2 Auerbach DS et al. Altered Cardiac Electrophysiology and SUDEP in a Model of Dravet Syndrome. PLoS One. 2013;8(10).
3 Lopez-Santiago LF et al. Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. J Mol Cell Cardiol. 2007;43(5):636-47.
4 Frasier CR et al. Cardiac arrhythmia in a mouse model of SCN8A Epileptic Encephalopathy. Proc Natl Acad Sci U S A. 2016; in press.
5 Frasier CR et al. Channelopathy as a SUDEP Biomarker in Dravet Syndrome Patient Derived Cardiac Myocytes. Stem Cell Reports. 2018 Sep 11;11(3):626-634.