Posts Tagged SUDEP

[WEB SITE] New epilepsy warning device could save thousands of lives — ScienceDaily

Nightwatch bracelet on the arm of a young epilepsy patient.
Credit: LivAssured

A new high-tech bracelet, developed by scientists from the Netherlands detects 85 percent of all severe night-time epilepsy seizures. That is a much better score than any other technology currently available. The researchers involved think that this bracelet, called Nightwatch, can reduce the worldwide number of unexpected night-time fatalities in epilepsy patients. They published the results of a prospective trial in the scientific journal Neurology.

SUDEP, sudden unexpected death in epilepsy, is a major cause of mortality in epilepsy patients. People with an intellectual disability and severe therapy resistant epilepsy, may even have a 20% lifetime risk of dying from epilepsy. Although there are several techniques for monitoring patients at night, many attacks are still being missed.

Consortium researchers have therefore developed a bracelet that recognizes two essential characteristics of severe attacks: an abnormally fast heartbeat, and rhythmic jolting movements. In such cases, the bracelet will send a wireless alert to carers or nurses.

The research team prospectively tested the bracelet, known as Nightwatch, in 28 intellectually handicapped epilepsy patients over an average of 65 nights per patient. The bracelet was restricted to sounding an alarm in the event of a severe seizure. The patients were also filmed to check if there were any false alarms or attacks that the Nightwatch might have missed. This comparison shows that the bracelet detected 85 percent of all serious attacks and 96% of the most severe ones (tonic-clonic seizures), which is a particularly high score.

For the sake of comparison, the current detection standard, a bed sensor that reacts to vibrations due to rhythmic jerks, was tested at the same time. This signalled only 21% of serious attacks. On average, the bed sensor therefore remained unduly silent once every 4 nights per patient. The Nightwatch, on the other hand, only missed a serious attack per patient once every 25 nights on average. Furthermore, the patients did not experience much discomfort from the bracelet and the care staff were also positive about the use of the bracelet.

These results show that the bracelet works well, says neurologist and research leader Prof. Dr. Johan Arends. The Nightwatch can now be widely used among adults, both in institutions and at home. Arends expects that this may reduce the number of cases of SUDEP by two-thirds, although this also depends on how quickly and adequately care providers or informal carers respond to the alerts. If applied globally, it can save thousands of lives.

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Materials provided by Eindhoven University of TechnologyNote: Content may be edited for style and length.

Journal Reference:

  1. Johan Arends, Roland D. Thijs, Thea Gutter, Constantin Ungureanu, Pierre Cluitmans, Johannes Van Dijk, Judith van Andel, Francis Tan, Al de Weerd, Ben Vledder, Wytske Hofstra, Richard Lazeron, Ghislaine van Thiel, Kit C.B. Roes, Frans Leijten. Multimodal nocturnal seizure detection in a residential care settingNeurology, 2018; 10.1212/WNL.0000000000006545 DOI: 10.1212/WNL.0000000000006545

via New epilepsy warning device could save thousands of lives — ScienceDaily

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[WEB SITE] New Epilepsy Bracelet Could Save Thousands of Lives

High-Tech “Nightwatch” is Capable of Detecting 85 Percent of Severe Night-Time Epileptic Seizures

Scientists in the Netherlands are optimistic that their new device will reduce the number of sudden unexpected death in epilepsy (SUDEP) patients worldwide. Currently, for people with an intellectual disability and severe treatment-resistant epilepsy, the outlook is poor, with a possible 20 percent lifetime risk of dying from epilepsy. While several techniques exist for monitoring patients at night, many seizures are still being missed.

With this in mind, a consortium of researchers (from Kempenhaeghe epilepsy centre, Eindhoven University of Technology, the Foundation for Epilepsy Institutions in the Netherlands (SEIN), UMC Utrecht, the Epilepsy Fund, patient representatives, and LivAssured) developed Nightwatch, a bracelet that recognizes unusually fast heartbeat and rhythmic jolting movements, two critical characteristics of severe attacks. When these occur, the device sends a wireless alert to caregivers or nurses.

In a test among 28 intellectually handicapped patients with epilepsy, over an average of 65 nights, Nightwatch detected 85 percent of all serious attacks and 96 percent of the most severe ones (tonic-clonic seizures). In comparison, a bed sensor, which is the current detection standard, sounded the alarm for only 21 percent of serious attacks. While the bed sensor was silent once every four nights per patient, the Nightwatch only missed a serious attack once every 25 nights, on average.

Prof. Dr. Johan Arends, neurologist and research leader, expects that the bracelet may reduce the number of SUDEP cases by two-thirds, although this also depends on the speed and efficiency with which caregivers respond to the alerts.

Source:, October 29, 2018


via New Epilepsy Bracelet Could Save Thousands of Lives | Managed Care magazine

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[Abstract] Dead in the water: Epilepsy‐related drowning or sudden unexpected death in epilepsy?



Both drowning and sudden unexpected death in epilepsy (SUDEP) are diagnoses of exclusion with predominantly nonspecific autopsy findings. We hypothesized that people with epilepsy found dead in water with no clear sign of submersion could be misdiagnosed as SUDEP.


All reported seizure‐related deaths undergoing medicolegal investigation in three medical examiner’s offices (New York City, Maryland, San Diego County) over different time periods were reviewed to identify epilepsy‐related drownings and SUDEPs. Drowning cases that fulfilled inclusion criteria were divided into two groups according to the circumstances of death: definite drowning and possible drowning. The SUDEP group included two sex‐ and age (±2 years)‐matched definite SUDEP/definite SUDEP plus cases for each drowning case.


Of 1346 deaths reviewed, we identified 36 definite (76.6%) and 11 possible drowning deaths (23.4%), most of which occurred in a bathtub (72.3%). There were drowning‐related findings, including fluid within the sphenoid sinuses, foam in the airways, clear fluid in the stomach content, and lung hyperinflation in 58.3% (21/36) of the definite drowning group, 45.5% (5/11) of the possible drowning group, and 4.3% of the SUDEP group (4/92). There was no difference in the presence of pulmonary edema/congestion between the definite drowning group, possible drowning group, and SUDEP group. The definite drowning group had a higher mean combined lung weight than the SUDEP group, but there was no difference in mean lung weights between the possible drowning and SUDEP groups or between the possible drowning and definite drowning groups.


No distinguishable autopsy finding could be found between SUDEPs and epilepsy‐related drownings when there were no drowning‐related signs and no clear evidence of submersion. SUDEP could be the cause of death in such possible drowning cases. As most drowning cases occurred in the bathtub, supervision and specific bathing precautions could be effective prevention strategies.


via Dead in the water: Epilepsy‐related drowning or sudden unexpected death in epilepsy? – Cihan – – Epilepsia – Wiley Online Library



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[WEB SITE] Mechanisms of Ketogenic Diet Identify Novel Targets for AED Development

Diet restriction is an ancient method for control of epileptic seizures, though a precise understanding of how it mediates seizure suppression is still unknown. Development of the high-fat, low-carbohydrate, protein-adequate ketogenic diet (KD) was based on the hypothesis that ketone production induced by glucose deprivation is responsible for the historic seizure-suppressing effect of fasting. Recently, several key findings regarding how the ketogenic diet suppresses seizures in patients with refractory epilepsy have revealed new targets for anti-epileptic drug design as well as novel therapeutic approaches for epilepsy.

The traditional KD involves a strict 4:1 ratio by weight of fat to combined carbohydrate and protein. A more recently developed modified KD- the medium-chain triglyceride (MCT) diet- is more ketogenic, and thus allows greater intake of carbohydrates and proteins, easing compliance and improving nutrition. Despite this modification, adherence is so difficult that the KD is reserved for use in patients whose seizures do not respond to anti-epileptic drug (AED) treatment.1

While most epileptics become seizure free with AED treatment, roughly 30% of patients will continue to have seizures despite taking multiple AEDs.Uncontrolled seizures not only limit quality of life, but are also associated with risk of sudden unexpected death in epilepsy (SUDEP),highlighting the need for improved understanding of alternative interventions.

Medically refractory epileptics have few treatment options, including brain surgery, vagus nerve stimulation, and KD. While numerous clinical reports indicate the efficacy of KD for treatment of drug-resistant epilepsy, few high-quality controlled studies exist.The most recent Cochrane Review of KD for treatment of epilepsy states that seizure freedom rates after 3 months on a 4:1 classic KD can reach up to 55%, while rates of seizure reduction reach as high as 85%.However, compliance is difficult, emphasizing the need to better understand how the KD works to facilitate development of supplements that may provide the “ketogenic diet in a pill.”4

General mechanism of action of the ketogenic diet

The KD imparts its effect via multiple pathways. In general, it is believed that the KD works by decreasing neuronal excitability, decreasing inflammation, and improving mitochondrial function, either through the direct action of ketone bodies and fatty acids, or through downstream changes in metabolic and inflammatory pathways.

Several specific mechanisms have been suggested by studies performed in vitro or in animal models of epilepsy, including: 1) direct action of ketone bodies; 2) direct action of fatty acids; 3) glycolic restriction or diversion; 4) altered neurotransmitter systems involving GABA, glutamate, and adenosine; 5) changes in ion channel regulation; 6) improved mitochondrial function and cellular bioenergetics; 7) a reduction in oxidative stress; and 8) enhancement of the tricarboxylic acid (TCA) cycle.While data support a role for each of these pathways in seizure control, several recent studies have identified precise molecules that regulate specific pathways involved in seizure suppression. These molecules may thus serve as targets for drug development that could provide the same effects as the KD without the need for diet restriction.


Direct inhibition of AMPA receptors by decanoic acid controls seizures

Decanoic acid, a medium-chain fatty acid that penetrates the blood-brain barrier, has previously been shown to 1) improve mitochondrial biogenesis through a peroxisome proliferator-activated receptors (PPAR)y-mediated mechanism; 2) increase transcription of genes regulating fatty acid metabolism while downregulating genes involved in glucose metabolism; and 3) modulate astrocyte metabolism and affect the glial/neuronal shuttle system by supplying neurons with ketones and lactate for fuel.However, a recent seminal study by Chang et al has now delineated a specific protein target of decanoic acid- the ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and has shown decanoic acid to have anti-seizure effects at clinically relevant doses.Using rat hippocampal slices and whole cell patch-clamp measurements, Chang et al demonstrated that decanoic acid, but not ketone bodies, had an inhibitory effect on neurotransmission, and that this effect is mediated through postsynaptic excitatory AMPA receptors. Importantly, this inhibitory effect was found at physiological serum concentration (0.3mM; 52 µg/ml) of decanoic acid, similar to that measured in children on the MCT diet, and below serum and brain concentrations that suppress seizures in mouse models of epilepsy. Also of note was that decanoic acid selectively blocks excitatory synaptic activity while not affecting inhibitory synaptic currents.5

Furthermore, by expressing AMPA receptor subunits in Xenopus oocytes and testing neuronal excitability in the presence of decanoic acid ± glutamate, the authors were able to conclude that decanoic acid inhibits the AMPA receptor by binding to a site that does not compete with glutamate binding.5

This binding is unique to decanoic acid, while octanoic acid and valproic acid do not interact with AMPA receptors.“If it were possible to replace the diet with an AMPA receptor antagonist, this would enormously simplify therapy, avoid the poor palatability and gastrointestinal side effects of the diet, and therefore make treatment available to a broader group of patients,” wrote Dr. Michael Rogawski in a commentary on the findings of Chang et al.5,6 As such, a comparative trial between the MCT KD diet and parampanel warrants consideration.

Inhibition of lactate dehydrogenase results in seizure suppression

While it is well known that the KD affects energy metabolism, metabolic enzymes that control epilepsy have not yet been identified. Similarly, no AEDs are known to directly impact metabolic pathways, though the mechanism of action of many AEDs remains unclear.In a landmark study published in Science, Sada et al investigated the mechanism by which glucose deprivation leads to neuronal hyperpolarization and subsequent seizure suppression. By simply switching the energy source from glucose to ketone bodies (as occurs on the KD), neurons from the subthalmic nucleus of the basal ganglia were dramatically hyperpolarized. However, addition of ketone bodies alone did not hyperpolarize the neurons; instead, Sada et al were able to show that glucose deprivation resulted in inhibition of lactate dehydrogenase (LDH), an enzyme that converts glucose to lactate in astrocytes, and that this inhibition alone is responsible for neuron hyperpolarization. Therefore, this study suggests it is the inhibition of LDH, and not activation of the tricarboxylic acid (TCA) cycle by ketone bodies, that mediates anti-seizure effects. Sada et al demonstrated that direct inhibition of LDH could suppress seizures both in vitro and in vivo (mouse), confirming LDH as a valid target for development of AEDs.

Taking their study one step further, the authors determined that a clinically used AED, stiripentol, binds to LDH and inhibits its activity. Sada et al were able to modify stiripentol into a derivative that more potently inhibited LDH and could suppress seizures in mice, suggesting that LDH inhibitors should be further explored as drugs that can mimic effects of the ketogenic diet.7

Epigenetic changes induced by the KD confer long-term seizure protection

While acute prevention of drug-refractory seizures is the primary goal of the KD, study of children following the diet suggests that KD may confer protection against seizures even after its discontinuation.8 A proposed mechanism has been recently outlined by Lusardi et al, who demonstrated that the KD reduced hippocampal DNA methylation to levels found in non-epileptic controls, resulting in delayed onset of severe seizures and slower disease progression.9 Importantly, this reduction was maintained over at least 8 weeks after diet reversal, suggesting a “recalibration” of brain chemistry. Similarly, another study found that the KD delayed disease progression and increased longevity by 47% and in mouse models of SUDEP.3 Since hypermethylation of hippocampal DNA is a hallmark of the epileptic brain, the finding that long-lasting epigenetic changes can be maintained in animals predisposed to severe epilepsy suggests that “recalibration” of the epileptic brain is possible. Drugs that increase hippocampal adenosine concentration to that achieved by the KD may prove effective at decreasing DNA methylation status in the epileptic brain,10 and should be pursued for treatment of drug-resistant epilepsy.

Ketogenic diet modification of gut microbiota

A new, recently identified physiologic change induced by the KD is alteration of the gut microbiome. Using a mouse model of Autism Spectrum Disorder (ASD), in which the KD has been shown to limit symptoms,11 Newell et al demonstrated remodeling of the gut microbiota, leading to lower bacterial load and altered composition.12 Interestingly, the authors point out a 2- to 3- fold increase in bacterial species that generate short-chain fatty acids (SCFAs) that actively communicate with the brain. Given the increasing evidence of a “gut-brain axis” and the knowledge that fatty acids play an active role in the epileptic brain, it will be important to determine what role this change in gut microbial composition may play in regulation of seizures.


Published: April 28, 2017



via Mechanisms of Ketogenic Diet Identify Novel Targets for AED Development

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[WEB SITE] Wristband devices may improve detection and characterization of epileptic seizures

New research published in Epilepsia (, a journal of the International League Against Epilepsy (ILAE), indicates that wristband devices may improve the detection and characterization of seizures in patients with epilepsy.

New devices are needed for monitoring epileptic seizures, especially those that can lead to sudden death. While rare, “sudden unexpected death in epilepsy” (SUDEP) is the most common cause of death in epilepsy, and it often occurs at night. The gold standard for monitoring seizures-video-electroencephalography- is available in epilepsy monitoring units but is an impractical procedure for daily life use. Therefore, clinicians often rely on patients and caregivers to report seizure counts, which are often inaccurate.

In their attempts to develop a better monitoring method, Giulia Regalia, PhD and Francesco Onorati, PhD, of Empatica Inc. in Milan, Italy and Cambridge, Massachusetts, and their colleagues examined the potential of automated, wearable systems to detect and characterize convulsive epileptic seizures. The researchers used three different wristbands to record two signals-called electrodermal activity and accelerometer signals-that usually exhibit marked changes upon the onset of convulsive seizures, obtaining 5928 hours of data from 69 patients, including 55 convulsive epileptic seizures from 22 patients.

The wristband detectors showed high sensitivity (95% of seizures were detected) while keeping the false alarm rate at a bearable level (on average, one false alarm every four days), which improves a pioneering 2012 study led by MIT professor Rosalind Picard, now chief scientist at Empatica.

In addition to detecting seizures, the method also revealed certain characteristics of the seizures, which may help alert clinicians and patients to seizures that are potentially dangerous and life-threatening.

“The present work provides significant improvements for convulsive seizure detection both in clinical and ambulatory real-life settings,” said Dr. Regalia. “Accurate seizure counts with real-time alerts to caregivers allows an early application of aid, which can be protective against SUDEP risk.” She noted that the wristband detectors do not require caregivers to be near patients continuously, which could significantly improve patients and caregivers’ quality of life.

Source: Wristband devices may improve detection and characterization of epileptic seizures

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[WEB SITE] A Look at Epilepsy – Electrical Outbursts in the Brain

Illustration of a man holding a child; a doctor and patient; and a brain.When you hear the word epilepsy, you might think of intense seizures with muscle spasms and loss of consciousness. But most epilepsy seizures are surprisingly subtle and may be hard to recognize. These little spells can be an early warning sign of epilepsy, a brain disorder that strikes an estimated 1 in 26 Americans at some point in their lives. The sooner epilepsy is recognized, the sooner it can be treated and seizures prevented.

Most people know surprisingly little about epilepsy, even though it’s the nation’s 4th most common neurological disorder, after migraine, stroke, and Alzheimer’s disease. Epilepsy is marked by repeated, unpredictable seizures that may last for seconds or minutes. Seizures arise from abnormal bursts of electrical activity in the brain that trigger jerky movements, strange emotions or sensations, falls, or passing out.

“Epilepsy can strike people of all ages, from the moment of birth—even in the delivery room—up to older ages,” says Dr. Jeffrey Noebels, an epilepsy expert at Baylor College of Medicine. The condition is most likely to first arise in children and in adults over age 60. “Most types of epilepsy last a lifetime, but some are self-limited, meaning they can go away on their own,” Noebels adds.

The causes of epilepsy are varied. “Defects in genes are probably responsible for the largest fraction of epilepsy cases,” Noebels says. Scientists so far have linked more than 150 genes to epilepsy. “Other types of epilepsy can be acquired through trauma (such as head injury or stroke), infections, brain tumors, or other factors.”

Anything that disrupts the normal pattern of brain activity—from illness to brain damage to faulty brain development—can lead to seizures. But for up to half of people with epilepsy, the underlying cause is simply not known.

Types of seizures can also vary widely, which is why epilepsy is sometimes called a “spectrum disorder.” In some people, seizures may appear only occasionally. At the other end of the spectrum, a person may have hundreds of seizures a day. The seizures can be severe, with convulsions, loss of consciousness, or even sudden death in rare cases. Or seizures may be barely noticeable.

Such subtle seizures—sometimes called partial or focal seizures—can cause feelings of déjà vu (feeling that something has happened before); hallucinations (seeing, smelling, or hearing things that aren’t there); or other seemingly mild symptoms. During some seizures, a person may stop what they’re doing and stare off into space for a few seconds without being aware of it.

“These little spells or seizures can sometimes occur for years before they’re recognized as a problem and diagnosed as epilepsy,” says Dr. Jacqueline French, who specializes in epilepsy treatment at the New York University Langone Medical Center. “They can be little spells of confusion, little spells of panic, or feeling like the world doesn’t look real to you.”

The symptoms of these small seizures generally depend on which brain regions are affected. Over time, these types of seizures can give rise to more severe seizures that affect the whole brain. That’s why it’s important to get diagnosed and begin epilepsy treatment as soon as possible. “If you notice a repeating pattern of unusual behaviors or strange sensations that last anywhere from a few seconds to a few minutes, be sure to mention it to your doctor or pediatrician,” French says.

Over the past few decades, NIH-funded scientists have been working to develop better approaches for diagnosing, treating, and understanding epilepsy. The condition can now be diagnosed through imaging tools like MRI or CT scans, by testing blood for defective genes, or by measuring the brain’s electrical activity. Seizures can often be controlled with medications, special diets, surgery, or implanted devices. But there’s still a need for improved care.

“Traditional medications for treating epilepsy are effective but problematic,” says Dr. Ivan Soltesz, who studies epilepsy at Stanford University. “About 1 in 3 patients has drug-resistant epilepsy, meaning that available drugs can’t control the seizures. In these cases, surgical removal of brain tissue may be the best option.” When the drugs do work, he explains, they can also cause numerous side effects, including fatigue, abnormal liver function, and thinking problems.

One issue with today’s medicines is they aren’t targeted to the malfunctioning brain cells. Rather, they tend to affect the whole brain. “The drugs are also not specific in terms of the timing of treatment,” Soltesz says. “The medications are always in the body, even when the seizures are not occurring.”

He and other researchers are working to create highly targeted epilepsy therapies that are delivered only to malfunctioning brain regions and only when needed to block a seizure. So far, they’ve developed an experimental approach that can stop epilepsy-like seizures as they begin to occur in a mouse. The scientists hope to eventually translate those findings for use in people who have epilepsy.

In another line of NIH-funded research, a team of scientists is studying a deadly and poorly understood condition called SUDEP (for sudden unexpected death in epilepsy). “Most people with epilepsy live long and happy lives. But SUDEP is the most common cause of the shorter lifespan that can occur with epilepsy,” says Noebels. “It’s been a real mystery. We haven’t known who’s at greatest risk for this premature death. It can happen to different people who have epilepsy, from all walks of life.”

Noebels and his colleagues have identified several mouse genes that seem related to both sudden-death seizures and heart rhythm problems. The researchers are now searching for similar human genes that may help predict who’s most at risk for SUDEP. “We believe that SUDEP doesn’t have to happen—that we can learn about it, predict it, and eventually find better ways to prevent it in every patient,” Noebels says.

You can take steps to reduce some risk factors for epilepsy. Prevent head injuries by wearing seatbelts and bicycle helmets, and make sure kids are properly secured in car seats. Get proper treatment for disorders that can affect the brain as you age, such as cardiovascular disease or high blood pressure. And during pregnancy, good prenatal care can help prevent brain problems in the developing fetus that could lead to epilepsy and other problems later in life.

“We’ve made exciting advances to date in our understanding of epilepsy, its prevention, and treatment,” says French. “But there’s still much we have to learn, and much we’re actively working to improve.”

The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia. Jehi L, Friedman D, Carlson C, Cascino G, et al. Epilepsia. 2015 Oct;56(10):1526-33. doi: 10.1111/epi.13116. Epub 2015 Aug 7. PMID: 26250432.

On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Krook-Magnuson E, Armstrong C, Oijala M, Soltesz I. Nat Commun. 2013;4:1376. doi: 10.1038/ncomms2376. PMID: 23340416.

Sudden unexpected death in epilepsy: Identifying risk and preventing mortality. Lhatoo S, Noebels J, Whittemore V; NINDS Center for SUDEP Research. Epilepsia. 2015 Nov;56(11):1700-6. doi: 10.1111/epi.13134. Epub 2015 Oct 23. PMID: 26494436.

NIH News in Health, November 2015

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