Tool Helps GPs Predict Risk of Epilepsy Seizures in Pregnancy

GPs, 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, to determine the need for close monitoring in pregnancy, labor, and after birth, and to assess antiepilepsy drug management, according to new UK-led 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.

Researchers from Queen Mary University, London, pointed out that pregnant women with epilepsy are at 10 times greater risk of dying during pregnancy than women without epilepsy; that consecutive reports of the Confidential Enquiry into Maternal Deaths have issued warnings on the failings in antenatal, intrapartum, and postnatal management of women with epilepsy; and that up to four in 10 women discontinue their antiepilepsy medication in pregnancy because of concerns about the effects of drugs on their baby, thereby increasing their risk of seizures, and of complications from seizures. But despite this, they said, these women’s high-risk status during pregnancy and after childbirth is often not recognized.

They set out to develop and validate a prognostic model, using information collected during the antenatal booking visit, to predict seizure risk at any time in pregnancy and until six weeks postpartum in women with epilepsy on antiepileptic drugs, using datasets from the prospective multicenter EMPiRE (AntiEpileptic drug Monitoring in PREgnancy) study.

They concluded: “The EMPiRE model performs well in predicting the risk of seizures at the time of antenatal booking in pregnant women with epilepsy who are prescribed antiepileptic medication. The model incorporates routinely available characteristics that are easy to measure, such as age at first seizure, type of seizures, seizures in the three months before pregnancy, mental health, admission to hospital for seizures during a previous pregnancy, and dose of antiepileptic drugs.”

Sex Bias in Autism Virtually Absent Among Those with Epilepsy

There are roughly as many autistic boys who have epilepsy as there are girls, according to a new meta-analysis.

The overall ratio of boys to girls among children diagnosed with autism is 3-to-1. Scientists have suggested many theories for this sex bias: that girls are partially protected from mutations that cause the condition, for example.

The new work suggests seizure disorders override this protection.

“This could be because the usual female protection against neurodevelopmental disorders is overcome when there is a chronic brain illness,” says co-lead researcher Eric Taylor, emeritus professor of child and adolescent psychiatry at King’s College London.

Another possibility is that because girls with epilepsy see doctors often, they are more likely to be diagnosed with autism than other autistic girls.

A Call for Better Information about Epilepsy: The Patients’ Perspective – An Online Survey

PURPOSE: For people with epilepsy (PWE), insufficient information and knowledge about the disease might have a negative influence on outcome and lead to poorer quality of life. In contrast, good information may increase empowerment and reduce stigma. This study investigated whether Norwegian PWE want information about different epilepsy-related issues, whether they actually obtain the information that they seek, and the extent to which they are satisfied with the information they receive. Furthermore, this study examined which factors might have influenced the degree of specific information given to PWE.

METHODS: The research team invited PWE visiting the homepage of the Norwegian Epilepsy Association to complete a web-based questionnaire about their perspective on obtaining information about epilepsy-related issues. The survey was accessible for a four-month period during 2017.

RESULTS: More than 90% of respondents (n = 1182) wanted general information about epilepsy, and over 75% wanted information on more specific issues, like epilepsy surgery. Depending on the subject, the proportion of respondents that reported receiving the information they wished varied from 6.6% to 91.9%. Obtaining information about epilepsy surgery and neurostimulation was significantly associated with male gender. Having tonic-clonic seizures was associated with obtaining information about the diagnosis, an organized lifestyle, regular sleep, and consumption of alcohol.

CONCLUSIONS: This study provides insights on how people with epilepsy experience provision of relevant information about epilepsy. Although most people with epilepsy considered that they obtained information on general epilepsy issues, most people with epilepsy interested in information on non-medical treatments and psychosocial issues reported that they did not obtain the information they wanted.

Meta-Analysis and Systematic Review Supports the Recommendation Against Prophylactic Antiepileptic Drugs After Acute Intracerebral Hemorrhage

PURPOSE: The purpose of this analysis is to assess the effect of antiepileptics (AEDs) on seizure prevention and short and long term functional outcomes in patients with acute intracerebral hemorrhage.

METHOD: The meta-analysis was conducted using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochrane Library, and EMBASE databases. Search terms included “Anticonvulsants”, “Intracerebral Hemorrhage”, and related subject headings. Articles were screened and included if they were full-text and in English. Articles that did not perform multivariate regression were not included. Overall effect size was evaluated with forest plots and publication bias was assessed with the Begg’s and Egger’s tests.

RESULTS: A total of 3912 articles were identified during the initial review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. No significant association between the use of AEDs after ICH and functional outcome (OR 1.53 [95%CI: 0.81-2.88] P = 0.18, I2 = 81.7%). Only one study evaluated the effect AEDs had in preventing post-ICH seizures.

CONCLUSIONS: The use of prophylactic antiepileptic drugs was not associated with improved short and long outcomes after acute intracerebral hemorrhage. This analysis supports the 2015 AHA/ASA recommendation against prophylactic antiepileptic drugs (class III; level of evidence b).

Review article: “Autoimmune Epilepsy”: Encephalitis with Autoantibodies for Epileptologists

Autoimmune encephalitides may account for epilepsies of so far unknown cause. These “autoimmune epilepsies” may respond well to immunotherapy. More than a dozen autoantibodies have been found with this constellation; therefore, broad autoantibody testing of serum-CSF pairs offers the best diagnostic yield. Several particular features raise the suspicion of an autoimmune cause in otherwise unexplained seizure disorders.

UK Report: People with Epilepsy Twice as Likely as Average to Be Unemployed

In the UK approximately 1 in 100 people (600,000) have a diagnosis of epilepsy, yet despite anti-discrimination legislation, people with epilepsy in the UK are more than twice as likely as those without the condition to be unemployed. That is the main conclusion of a report from IES which included a literature review, interviews with for experts in employment support, clinical practice and applied research, interviews with six employers of different sizes across a range of industries and two focus groups of individuals with varied symptoms and employment histories.

The report explores factors that contribute to people with epilepsy being disadvantaged at work and to identify what good employment support should look like. The research uncovered clear employer knowledge gaps, underpinned by a lack of awareness surrounding the fluctuating condition. Equally, employees were often very reluctant to discuss their health with employers until firmly established in the workplace – for fear of discrimination.

The employers interviewed were often unfamiliar with the range of symptoms that exist, sometimes unaware that medication can often prevent seizures – the chief health and safety concern cited when considering employing somebody with epilepsy. Employers frequently doubted that they could make adjustments to enable someone with epilepsy to work safely. Job roles involving machinery, vehicles, working remotely or alone, or caring for others were felt to be particularly difficult.

Study Reveals How Glial Cells May Play Key Epilepsy Role

A study provides potential new targets for treating epilepsy and novel fundamental insights into the relationship between neurons and their glial “helper” cells. In eLife, scientists at MIT’s Picower Institute for Learning and Memory report finding a key sequence of molecular events in which the genetic mutation in a fruit fly model of epilepsy leaves neurons vulnerable to becoming hyper activated by stress, leading to seizures.

About 60 million people worldwide have epilepsy, a neurological condition characterized by seizures resulting from excessive neural activity. The “zydeco” model flies in the study experience seizures in a similar fashion. Since discovering zydeco, the lab of MIT neurobiologist Troy Littleton, Menicon Professor in Neuroscience, has been investigating why the flies’ zydeco mutation makes it a powerful model of epilepsy.

Heading into the study, the team led by postdoc Shirley Weiss knew that the zydeco mutation was specifically expressed by cortex glial cells and that the protein it makes helps to pump calcium ions out of the cells. But that didn’t explain much about why a glial cell’s difficulty maintaining a natural ebb and flow of calcium ions would lead adjacent neurons to become too active under seizure-inducing stresses such as fever-grade temperatures or the fly being jostled around.

The activity of neurons rises and falls based on the flow of ions – for a neuron to “fire,” for instance, it takes in sodium ions, and then to calm back down it releases potassium ions. But the ability of neurons to do that depends on there being a conducive balance of ions outside the cell. For instance, too much potassium outside makes it harder to get rid of potassium and calm down.

The need for an ion balance – and the way it is upset by the zydeco mutation – turned out to be the key to the new study. In a four-year series of experiments, Weiss, Littleton and their co-authors found that excess calcium in cortex glia cells causes them to hyper-activate a molecular pathway that leads them to withdraw many of the potassium channels that they typically deploy to remove potassium from around neurons. With too much potassium left around, neurons can’t calm down when they are excited, and seizures ensue.

“No one has really shown how calcium signaling in glia could directly communicate with this more classical role of glial cells in potassium buffering,” Littleton said. “So this is a really important discovery linking an observation that’s been found in glia for a long time – these calcium oscillations that no one really understood – to a real biological function in glial cells where it’s contributing to their ability to regulate ionic balance around neurons.”

High-Dose Oral Vitamin D3 Appears Safe and Well-Tolerated in Epilepsy

Vitamin D3 in high doses was safe and well-tolerated in patients with epilepsy and never exceeded toxic levels, according to study results published in Epilepsy & Behavior.

Researchers sought to examine the tolerability of vitamin D3 in an ongoing trial of vitamin D3 5000 IU/d intended to reduce seizures in drug-resistant epilepsy. Inclusion criteria were that participants should have greater than or equal to 1 focal onset or generalized tonic-clonic seizure per month and must have been treated with greater than or equal to 2 antiepileptic drugs (AEDs) alone or in combination at effective doses without becoming seizure-free. Participants were to maintain a seizure calendar, and no changes in AED doses were allowed during the study.

Wireless Sensor Would Give Epilepsy Patients More Freedom

A team of electrical and computer engineering majors at Rice University’s Brown School of Engineering are developing an instrument to gather signals from a patient’s brain and send them to the computer wirelessly.

They hope their effort, part of the seniors’ capstone design requirement, will someday aid patients with epilepsy of the sort that medications can’t help, but may require surgical removal of small parts of the brain where seizures originate. First, doctors must figure out which parts are relevant, and to do so requires implanting electrodes that collect data during seizures.

“That means patients need to be in the hospital for a long enough period to get the large sample size of seizures they need to understand where they’re coming from,” junior Aiden Curtis says. “There are a lot of costs associated with that, including psychological costs. Patients have to stay connected, and can’t move around. They can’t go home.”

Clinicians Urged to Heighten Awareness Regarding Seizure-Associated Fractures

A systematic review of bone fractures from generalized convulsive seizures and status epilepticus

Abstract

Objective: Researchers present a systematic review of the literature regarding types and anatomic distribution of fractures in association with generalized convulsive status epilepticus (GCSE) and convulsive seizures in adult patients accompanied by an illustrative case of a patient with GCSE and diffuse postictal pain from underlying bone fractures.

Methods: The library search engines PubMed and EMBASE were screened systematically using predefined search terms. All identified articles written in English were screened for eligibility by two reviewers. The preferred reporting items for systematic reviews and meta-analyses guidelines were followed.

Results: The screening of 3145 articles revealed 39 articles meeting the inclusion criteria. Among all fractures, bilateral posterior fracture-dislocations of the shoulders were reported most frequently (33%), followed by thoracic and lumbar vertebral compression fractures (29%), skull and jaw fractures (8%), and bilateral femoral neck fractures (6%). Risk factors for seizure-related fractures are seizure severity, duration of epilepsy, the use of antiseizure drugs known to decrease bone density, and a family history of fractures. Based on these findings, a three-step screening procedure is proposed to uncover fractures in the postictal state. All studies were retrospective without standardized screening methods for seizure-associated fractures resulting in a very low level of evidence and a high risk of bias.

Significance: Posterior fracture-dislocations of the shoulders, thoracic and lumbar vertebral compression, fractures of the skull and jaw, and bilateral femoral neck fractures are most frequently reported. Preventive measures including bone densitometry, calcium/vitamin D supplementation, and bisphosphonate therapy should be reinforced in epilepsy patients at risk of osteoporosis. As long as the effect of standardized screening of fractures is not investigated, it is too early to integrate such a screening into treatment guidelines. In the meantime, clinicians are urged to heighten awareness regarding seizure-associated fractures, especially in patients with postictal pain, as symptoms can be unspecific and misinterpretation may impede rehabilitation.