A proposed Guideline for Vagus Nerve Stimulator Handling in Palliative Care and After Death

Abstract, published in Epilepsia

Vagus nerve stimulation (VNS) is often used for patients with drug-resistant epilepsy. Although this intervention may improve seizure control and mood, multiple factors must be considered when patients with VNS near end of life. Researchers reviewed relevant literature to create a proposed guideline for management of patients with VNS in palliative care and after death. VNS has multiple possible side effects, including cough and swallowing difficulties. For patients with neurologic disease in palliative care, such adverse effects can severely affect quality of life and increase the risk for complications such as aspiration pneumonia, which is a type of lung infection due to a large amount of material from the stomach or mouth entering the lungs. Patients with VNS should be screened regularly for such side effects, and VNS parameters should be adjusted if they are identified.

If a patient requires urgent cardiac resuscitation involving external defibrillation, which is a technique that uses an electric shock to reset the normal rhythms of the heart, the VNS should be interrogated immediately afterwards to evaluate its function. During defibrillation, paddles should be placed perpendicular to the VNS, and as far as possible away from it. The VNS can be acutely turned off by taping the magnet to the patient’s chest, thereby preventing any possible interference with restoration of a normal heart rhythm.

After death, any staff involved with handling the body should be notified that a VNS is in place. The device must be removed prior to cremation, as it can explode with high heat. If the cause of death is unclear, a full postmortem examination should be undertaken, according to sudden unexpected death in epilepsy guidelines. If there is concern about device malfunction, the device should be returned to the manufacturer for evaluation.

Colorized scanning electron micrograph of a cell showing morphological signs of apoptosis, infected with SARS-COV-2 virus particles (orange), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.

Genetic Epilepsies and COVID-19 Pandemic: Lessons from the Caregiver Perspective

Abstract, published in Epilepsia

The COVID-19 pandemic represents an unprecedented international crisis with significant health, economic, and social consequences. This scenario has forced the medical community to face new practical and ethical challenges that require rapid responses. Early data show a variety of neurological manifestations in a significant proportion of patients who have been infected with the COVID-19 virus, although there is little documentation of the effects on people with epilepsy.

In this study, the research team assesses the impact of the COVID-19 pandemic in a particularly vulnerable population: individuals with genetic developmental and epileptic encephalopathies (DEEs), which comprise a group of brain disorders, and their caregivers. Although children appear to present milder COVID-19 manifestations, patients with DEEs present an increased susceptibility to certain triggers related to viral infections and respiratory comorbidities, are at risk of missing medical follow-up and emergency assistance due to health care resource allocation focus on COVID-19 patients, and are exposed to broader sociopsychological impact related to lockdown.

Therefore, this study evaluates the impact of the pandemic on patients with genetic DEEs and their caregivers in Spain, one of the current hotspots of the pandemic.

Cognitive Behavioral Therapy Reduces the Impact of Psychogenic Nonepileptic Seizures

Scientists have found that adding cognitive behavioral therapy (CBT) to standardized medical care gives patients with psychogenic nonepileptic seizures (PNES) longer periods of seizure freedom, less bothersome seizures and a greater quality of life, in a study published in Lancet Psychiatry today and by the Cognitive behavioral therapy for adults with PNES study group funded by National Institute for Health Research (NIHR).

PNES, also called dissociative seizures, look similar in appearance to epileptic seizures or fainting but are related to a different type of involuntary blackout that is typically distressing and disabling for patients and their carers. Up to 1 in 5 adults presenting in epilepsy clinics have this hidden condition which is one of several types of Functional Neurological Disorder (FND). Historically patients with PNES have often been ignored or disbelieved by doctors and research on treatment is limited. They are more likely to be found in women and usually have a poor outcome with a worse quality of life than people with epilepsy alone. People with PNES have a marked increase in health service use.

In the largest treatment trial to date for PNES, 368 patients from centers across England, Scotland, and Wales were followed up 6 months and 12 months after treatment courses began. Researchers found patients treated with PNES specific CBT alongside standardized medical care reported the highest number of consecutive dissociative seizure-free days in the previous 6 months, along with greater functional status, self-rated and doctor-rated change in global impression scores, and satisfaction with treatment when compared with standardized medical care alone.

Lead author Laura Goldstein, Professor of Clinical Neuropsychology at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London said, “We have delivered the first large-scale multi-center and multi-professional trial investigating treatments for adults with PNES. This is especially important as the availability of treatment for people with this disorder has been so variable in the UK and elsewhere.

While overall there appeared to be a reduction in how often people in both groups of the study were having PNES at the end of the trial, with no clear difference between the groups, the group who had received our package of PNES-specific CBT were reporting better functioning across a range of everyday situations. They described their PNES as less bothersome, they were less distressed, reported better health and fewer symptoms, and were more satisfied with their treatment. It is important to consider providing dissociative seizure-specific CBT in addition to specialist care from neurologists and psychiatrists to treat people with dissociative seizures.”

In the UK, there is currently no standardized care pathway for people with PNES. The researchers recommend the incorporation of seizure-specific CBT within specialist care from neurologists and psychiatrists. Furthermore, as participants received treatment in varied medical settings, this study suggests that the CBT combination intervention does not have to be limited to highly specialized centers and can be delivered by a range of clinical psychologists or cognitive behavioral psychotherapists. Researchers suggest future work is needed to identify which patients would benefit most from a dissociative seizure-specific CBT approach.

Neurologist, Professor Jon Stone, who was a co-investigator in the study said, “The CODES Trial is a landmark study for a condition which has, for too long, been ignored by health services. The trial has encouraged participating neurologists, psychiatrists and psychotherapists across the UK to raise their standard of care for these patients. The trial has set a new bar for evidence in this area, making it clear that there are thousands of new patients with this condition in the UK every year who we need to keep doing better for in terms of treatment and research in the future.”

Co-investigator Trudie Chalder, Professor of Cognitive Behavioural Psychotherapy at IoPPN, said, “With appropriate training and supervision, we now have evidence for the effectiveness of PNES specific CBT combined with standardized medical care. This is good news for patients who have often felt misunderstood and health care professionals (HCP’s) who have wanted guidance on best practice.”

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Notes to editors

To find out more and for a copy of the embargoed paper, or to arrange interviews, please contact the Communications team at NIHR Maudsley BRC:

  • Alex Booth, Communications and Engagement Manager, NIHR Maudsley Biomedical Research Centre, Tel 020 7848 0495 alex.booth@kcl.ac.uk
  • Serena Rianjongdee, Communications and Engagement Officer, NIHR Maudsley Biomedical Research Centre, Tel 020 7848 2137 serena.rianjongdee@kcl.ac.uk

Further information about Dissociative Seizures

To find out more about Dissociative Seizures and the umbrella condition, Functional Neurological Disorder you can read more at

http://www.codestrial.org

http://www.neurosymptoms.org

http://www.nonepilepticattack.info

http://www.fndhope.org

http://www.fndaction.org.uk

The National Institute for Health Research (NIHR) is the nation’s largest funder of health and care research. The NIHR:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.

This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. http://www.nihr.ac.uk/patientdata

About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience

King’s College London is one of the top 10 UK universities in the world (QS World University Rankings, 2018/19) and among the oldest in England. King’s has more than 31,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff.

The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London is the premier centre for mental health and related neurosciences research in Europe. It produces more highly cited publications in psychiatry and mental health than any other university in the world (Scopus, 2016), with 31 of the most highly cited scientists in this field. World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness and other conditions that affect the brain. http://www.kcl.ac.uk/ioppn

Individualizing the Definition of Seizure Clusters Based on a New Clustering Analysis

Abstract, published in Epilepsy Research

Objective: Seizure clusters are often encountered in people with poorly controlled epilepsy. Detection of seizure clusters is currently based on simple clinical rules, such as two seizures separated by four or fewer hours or multiple seizures in 24 hours. Current definitions fail to distinguish between statistically significant clusters and those that may result from natural variation in the person’s seizures. Ability to systematically define when a seizure cluster is significant for the individual carries major implications for treatment. However, there is no uniform consensus on how to define seizure clusters. This study proposes a statistical approach to defining seizure clusters that addresses these issues.

Methods: A total of 533,968 clinical seizures from 1,748 people with epilepsy in the Seizure Tracker™ seizure diary database were used for model development.

Results: Seizure clustering was present in 26.7% of people with epilepsy. Using the proposed model, we found that 37.7-59.4% of seizures identified as clusters based on routine definitions had a high probability of occurring by chance. Several clusters identified by our model were missed by conventional definitions.

Significance: This study proposes a statistical approach to individualized seizure cluster identification and demonstrates potential for real-time clinical usage through our new model this team has name ClusterCalc. Using this approach accounts for individual variations in baseline seizure frequency and evaluates statistical significance. This new definition has the potential to improve individualized epilepsy treatment by systematizing identification of unrecognized seizure clusters and preventing unnecessary intervention for random events previously considered clusters.

Students at a library

Digital Conversations about Suicide among Teenagers and Adults with Epilepsy: A Big-Data, Machine Learning Analysis

Abstract, published in Epilepsia

Objective: Digital media conversations can provide important insight into the concerns and struggles of people with epilepsy (PWE) outside of formal clinical settings and help generate useful information for treatment planning. This study aimed to explore the big data from open-source digital conversations among PWE with regards to suicidality, specifically comparing teenagers and adults, using machine learning technology.

Methods: Advanced machine-learning empowered methodology was used to mine and structure open-source digital conversations of self-identifying teenagers and adults who endorsed suffering from epilepsy and engaged in conversation about suicide. The search was limited to 12 months and included only conversations originating from US internet addresses.

Results: A total of 222,000 unique conversations about epilepsy, including 9,000 (4%) related to suicide, were posted during the study period. The suicide-related conversations were posted by 7.8% of teenagers and 3.2% of adults in the study. Several critical differences were noted between teenagers and adults. A higher percentage of teenagers are; fearful of “the unknown” due to seizures (63% vs 12% adults), concerned about social consequences of seizures (30% vs 21%), and seek emotional support (29% vs 19%). In contrast, a significantly higher percentage of adults show a defeatist (“given up”) attitude compared to teenagers (42% vs 4%). There were important differences in the author’s determined sentiments behind the conversations among teenagers and adults.

Significance: In this first of its kind, big-data analysis of nearly a quarter-million digital conversations about epilepsy using machine learning, this research team found that teenagers engage in an online conversation about suicide more often than adults. There are some key differences in the attitudes and concerns, which may have implications for the treatment of younger patients with epilepsy.

A blond woman cradles her infant in her arms, trying to soothe them.

Levetiracetam (Keppra®) Versus Phenobarbital (Solfoton®) for Seizures in Newborn Children: A Randomized Controlled Trial

Abstract, published in Pediatrics

BACKGROUND AND OBJECTIVES: There are no US Food and Drug Administration–approved therapies for neonatal seizures, which are seizures that occur in newborn children. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in newborn children. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures.

METHODS: The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the pattern of brain waves by 2 neurophysiologists.

RESULTS: Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam. A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. Although more adverse effects were seen in subjects randomly assigned to phenobarbital, they were not statistically significant.

CONCLUSIONS: In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.

A close-up shot of a white person filling out a survey or forms with a silver pen.

Clinical Implementation of a Parent Questionnaire to Identify Seizures in High-Risk Children

In the present study, the researchers sought to assess the effectiveness of a parent-completed questionnaire for detecting seizures in high-risk children. In 12 Massachusetts clinics serving populations with high health disparities, a 2-part seizure screen for children up to 12 years old with suspected autism spectrum disorder, developmental delay, or seizure, was introduced. In a diverse population of high-risk children, the seizure questionnaire successfully detected seizures and other disorders. Broader use of this low-cost screening method may improve access to treatment for children with suspected seizures, increase awareness of seizures and more efficiently allocate resources.

EEG Reading

Rodent EEG: Expanding the Spectrum of Analysis

Abstract, published in Sage Journal

In epilepsy research, the analysis of rodent electroencephalogram (EEG) has been performed by many laboratories with a variety of techniques. However, the acquisition and basic analysis of rodent EEGs have only recently been standardized.

Since a number of software platforms and increased computational power have become widely available, advanced rodent EEG analysis is now more accessible to investigators working with rodent models of epilepsy. In this review, the approach to the analysis of rodent EEG will be examined, including the evaluation of both epileptiform and background activity.

The team also reviewed major caveats when employing these analyses, cellular and circuit-level correlates of EEG changes, and important differences between rodent and human EEG. The currently available techniques show great promise in gaining a deeper understanding of the complexities hidden within the EEG in rodent models of epilepsy.

A man checking his smart watch

Seizure Detection at Home: Do Devices on the Market Match the Needs of People Living with Epilepsy and Their Caregivers?

Abstract, published in Epilepsia

In patients with epilepsy, the potential to prevent seizure-related injuries and to improve the unreliability of seizure self-reporting have fostered the development and marketing of numerous seizure detection devices for home use. Understanding the requirements of users (patients and caregivers) is essential to improve adherence and mitigate barriers to the long-term use of such devices.

Here, researchers reviewed the evidence on the needs and preferences of users and provided an overview of currently marketed devices for seizure detection (medically approved or with published evidence for their performance). The team then compared devices with known needs. Seizure-detection devices are expected to improve safety and clinical and self-management, and to provide reassurance to users. Key factors affecting a device’s usability relate to its design (attractive appearance, low visibility, low intrusiveness), comfort of use, confidentiality of recorded data, and timely support from both technical and clinical ends. High detection sensitivity and low false alarm rates are paramount.

Currently marketed devices are focused primarily on the recording of non-electroencephalography (EEG) signals associated with tonic-clonic seizures, whereas the detection of focal seizures without major motor features remains a clear evidence gap. Moreover, there is paucity of evidence coming from real-life settings. A joint effort of clinical and nonclinical experts, patients, and caregivers is required to ensure an optimal level of acceptability and usability, which are key aspects for a successful continuous monitoring aimed at seizure detection at home.

Epilepsy Research Findings: May 2020

In this month’s epilepsy research news, we highlight an unexpected health benefit of epilepsy neurostimulators and report on a potential explanation for the effectiveness of fenfluramine in Dravet syndrome. We also present a study suggesting that people who have achieved long-term seizure freedom should speak with their doctors more often about the possibility of weaning off medications to reduce unnecessary drug burdens.

In addition, given the impact that the COVID-19 pandemic is having on all our lives, we feature two COVID-19 related articles: one examines the psychological well-being of people with epilepsy and the other highlights recommendations for patients, caregivers, and clinicians from a group of well-known neurologists.

Finally, we encourage you to participate in ongoing research about COVID-19’s impact on the rare disease community. Patients and caregivers who take this survey will help the rare disease research community shed light on their needs during the COVID-19 pandemic and future health crises.

Summaries of these articles are presented below:

Research News

  • Neurostimulators and Psychiatric Disorders: Brain wave recordings from responsive neurostimulator systems allow physicians to differentiate seizure-induced neurobehavioral symptoms from those caused by comorbid psychiatric disorders such as anxiety, depression, and psychosis. This additional information can help guide medication or therapy changes to target the psychiatric illness itself instead of similar symptoms brought on by the seizures themselves. Learn More
  • Fenfluramine and Dravet Syndrome: Researchers may have discovered how fenfluramine, which is currently being investigated as an add-on therapy to reduce seizures in people with Dravet syndrome, also seems to promote long-term improvements in cognition, behavior and emotional control. The beneficial effects of seizure reduction and cognitive enhancement may result from the drug’s synergistic effect on two different proteins found on the surface of nerve cells. Learn More
  • Antiseizure Drug (ASD) Withdrawal: A Norwegian survey found that people who have achieved long-term seizure-freedom are not talking to their doctors often enough about a plan for discontinuing drug treatment. This suggests that many patients may be living with an unnecessary drug burden. Learn More
  • COVID-19 and Psychological Distress: A study conducted at the epilepsy center of West China Hospital showed that people with epilepsy suffered from significantly more psychological distress compared to controls. The research found that independent predictors of this distress are time spent paying attention to COVID-19 and a diagnosis of drug-resistant epilepsy. Learn More
  • COVID-19, Epilepsy Management, and Safety: Leading neurologists published two key suggestions on caring for people with epilepsy during the COVID-19 pandemic. First, as much care as possible should be administered at home, including the strategic use of rescue therapies, to keep people out of health care facilities, where they are more likely to encounter COVID-19. Second, to minimize the risk of increased seizure severity or frequency, physicians should ensure that their patients adhere to treatment plans and have a regular supply of medication. Learn More
  • Rare Disease Community and COVID-19, a Survey: A new online survey created by the National Institute of Health aims to find out how the COVID-19 pandemic is impacting individuals with rare diseases, their families, and their caregivers. We encourage you to check it out! Learn More

In case you missed it! Our COVID-19 and Epilepsy Resource Hub is now live with resources to help families understand the potential impacts of COVID-19 on epilepsy care. This resource hub includes a guide to preparing for telehealth visits, recorded Q&A sessions, frequently asked questions, and more. Visit Now