[WEB] How common is Epilepsy?

Epilepsy – An Overview

Epilepsy is not one single condition. Rather, it is defined as a spectrum of disorders that involve abnormal activity within the brain. “Epilepsy” means the same thing as the term “seizure disorders.” In epilepsy, abnormal brain waves disturb electrical activity, leading to seizures. Symptoms of epileptic seizures include having unusual sensations or emotions, behaving in unusual ways, or experiencing convulsions or loss of consciousness. Brain damage, illness, and irregular brain development can all cause abnormal brain waves that lead to seizures.

Approximately half of all people who have had one seizure will have more (typically within six months). However, in order to be diagnosed with epilepsy, a person must have had more than one seizure, and doctors must consider it likely that they will continue to have seizures. When a person has a seizure that lasts for more than 5 minutes, or a person has more than one seizure within a 5 minutes period (without returning to consciousness between the seizures), it is called status epilepticus.

Some forms of epilepsy last for a limited time, although the condition is often lifelong. Although there is no cure currently for epilepsy, there are many treatments available for the condition. About 70 percent of people with seizures can control them with proper diagnosis and use of medication.

There are many different types of seizures, and some people with epilepsy will experience more than one type. Some examples of seizure types include:

• Absence seizures
• Generalized tonic-clonic seizures
• Atonic (or akinetic) seizures

The History of Epilepsy

People have been aware of epilepsy and seizures for millennia. A Babylonian medical textbook made up of 40 tablets and dating to 2000 B.C. contains a chapter that accurately describes many of the different types of seizures known today. However, seizures were thought to be supernatural in cause — each seizure type was associated with a different evil spirit or angry god — so the treatments prescribed were spiritual.

Epilepsy in Ancient Greece

The word “epilepsy” comes from the Greek word “epilepsia,” meaning “to seize” or “to take hold of.” By the 5th century B.C., the Greeks still considered epilepsy a “sacred” disease. Yet the renowned ancient physician Hippocrates described epilepsy as a brain disorder. This was a radical idea for the time. He recommended physical treatments while also recognizing that if the seizures became chronic, the disorder was incurable.

Despite Hippocrates’ writings, epilepsy continued to be considered a supernatural condition for the next two millennia. People with epilepsy were subjects of immense social stigma, treated as outcasts, and even punished as witches. In many places, people who suffered seizures were prevented from going to school, working, marrying, and having children. There were a few people with prominent positions thought to have had epilepsy — including Julius Caesar, Tsar Peter the Great of Russia, Pope Pius IX, and Fyodor Dostoevsky — but most people with epilepsy were prevented from living as full members of society.

Epilepsy in the 14th Century and Beyond

During the Renaissance, some scientists tried to prove epilepsy was a physical, not spiritual, illness. Then, in the 19th century, neurology became a recognized medical discipline and the idea of epilepsy as a brain disorder became normal in North America and Europe. In 1857, Sir Charles Lacock introduced bromide of potassium as the first antiepileptic drug (AED).

In 1873, a British neurologist named John Hughlings Jackson first described epilepsy as we understand it today. Jackson showed that seizures are caused by sudden, brief electrochemical discharges of energy in the brain. In 1909, the International League Against Epilepsy was founded as a global professional organization of epileptologists.

By the 1920s, Hans Berger, a German psychiatrist, had developed the electroencephalogram (EEG) to measure brain waves. It showed that each type of seizure is associated with a different brain wave pattern. The EEG also aided in the discovery that specific sites in the brain were responsible for seizures and expanded the potential for surgical treatments. Surgery became a more widely available option by the 1950s.

The Development of Antiepileptic Drugs

The medication phenobarbital was identified as an AED in 1912, and phenytoin (sold under the brand names Dilantin and Phenytek) was developed in 1938. Carbamazepine (sold under the brand names Tegretol and Carbatrol) was identified in 1953. These drugs have since been approved by the U.S. Food and Administration (FDA) and continue to be used today.

An accelerated drug-discovery process began in the 1970s with the creation of the Anticonvulsant Screening Program, sponsored by the National Institute of Neurological Disorders and Stroke. The program helped scientists gain a better understanding of the brain and epilepsy. Scientists have strived to reduce serious side effects associated with the use of older AEDs through drug-development processes.

Keppra (levetiracetam) was approved by the FDA in 1999. Several newer drugs, including Vimpat (lacosamide), Briviact (brivaracetam), and Aptiom (eslicarbazepine acetate), have been introduced in the past 10 to 15 years. Other promising medications are also in the pipeline.

Social Stigma

The stigma around epilepsy has lessened as more people are able to effectively treat their seizures. However, epilepsy largely remains an “invisible” illness. Millions of people in developing countries do not have access to AEDs, and stigma and discrimination are still widespread, especially in places where people still believe that seizures have a supernatural cause.

How Common Is Epilepsy?

People of all backgrounds, races, ethnicities, and ages are equally affected by epilepsy. It is estimated that epilepsy affects 1.2 percent of the population of the United States and more than 50 million people worldwide, making it one of the most common neurological disorders. Approximately 45,000 children under the age of 18 are diagnosed with epilepsy every year in the U.S., and roughly 10.5 million children worldwide live with epilepsy.

Diagnosing Epilepsy

Neuroimaging capabilities have improved over the past few decades. Magnetic resonance imaging (MRI), computerized tomography (CT) scans, and other techniques are able to detect more and more subtle brain lesions responsible for epilepsy.

Read more about diagnosing epilepsy.

Causes of Epilepsy

Causes of epilepsy include a wide variety of brain-related issues, such as structural damage, infectious diseases (like encephalitis), and genetic anomalies. Risk factors for epilepsy include:

• Age
• A family history of seizures
• Head injuries (such as traumatic brain injury or TBI)
• A history of seizures as a child

Read more about causes of seizures and epilepsy.

Types of Seizures

There are many types of epilepsy. Seizures are broken into two categories: focal seizures and generalized seizures. Focal seizures can be categorized by whether or not there is a loss of consciousness or awareness. Generalized seizures can be further broken down into absence, tonic, atonic, clonic, myoclonic, and tonic-clonic seizures.

Learn more about seizure types and symptoms of epilepsy.

Condition Guide

• Types of Epilepsy
• Causes of Seizures and Epilepsy
• Epilepsy — The Path to Diagnosis
• Seizure Types and Symptoms of Epilepsy
• Treatments for Epilepsy
• Conditions Related to Epilepsy

References

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[BLOG POST] Seizure medication side effects: what to do about them?

Seizure medication side effects can be very unpleasant. Learn about anti-seizure medication seizure effects and what to do about them

Have you recently started taking anti-epilepsy drugs (AEDs) and noticed medication side effects? Epilepsy medication side effects are very common – studies suggest that almost 60% of people on AED’s experience at least one side effect.

Here’s what you need to know about seizure medication side effects. 

What are seizure medication side effects?

Medication side effects are any kind of additional – and usually unwanted – effects of a medicine. With AEDs, the medication may bring your seizures under control, but they could also cause unpleasant feelings and physical symptoms.

There are many types of AED. Each of them works in different ways – and they all have different side effects. To find out about the specific side effects of your AED, read the leaflet that comes in the packet.  

Some of the more common seizure medication side effects include:

• Feeling tired and drowsy
• Feeling agitated (nervous or jumpy)
• Headaches
• Nausea (feeling like you’re going to be sick)
• Shaking and tremors
• Hypersensitivity (being strongly affected by noise or light)
• Hair loss
• Weight gain
• Mood changes, including low mood
• Rashes
• Swollen gums

There are many other possible epilepsy medication side effects which will be listed in the packaging of your AED. It’s also important to be aware that some side effects are ‘idiosyncratic’ – which means they’re unique to you.

How long do anti-seizure medication side effects last?

Oftentimes, seizure medication side effects will pass away on their own in a few weeks or months. Your body might just need to adjust to the medication. Eventually you will start feeling like yourself again.

That said, there are some chronic (long-lasting) side effects which you may notice over time. Monitoring these, and talking about them with your doctor, is important.

Dangerous seizure medication side effects

Most medication side effects are simply unpleasant or irritating and will go away on their own.

However, certain epilepsy medication side effects could be serious. If you notice that you have developed a rash somewhere on your body (usually within a couple of weeks of starting a new AED), it could mean you have developed an allergic reaction. If you continue taking the drug, it may have serious health consequences. Contact your epilepsy specialist immediately if you get a rash. 

There is also a small risk of liver or kidney damage associated with some AEDs. Your doctor will do blood tests to make sure they’re not causing any problems.

Side effects and quality of life

Most seizure medicine side effects will not seriously affect your health. All the same, they can be very inconvenient or unpleasant. For example:

• Some AEDs can cause weight gain which can be distressing.
• Another common epilepsy medication side effect is drowsiness. This can be extremely inconvenient if you need to focus at work, college or school.
• They may also cause hair loss or a loss of sexual desire.

While not life-threatening, these side effects can affect your quality of life. You should talk to your doctor if you notice them.

Special cases with AED side effects

There are certain situations where it is very important to be aware of seizure medication side effects:

• Pregnancy: If you are planning to become pregnant, you should talk to your doctor.  Because some types of anti-seizure medication may affect the baby’s health.
• Babies and young children: They may be unable to tell parents about any unpleasant feelings they are having. Special care should be taken to monitor their behavior and symptoms.
• People with learning difficulties: People with learning difficulties may also struggle to describe side effects. Carers should actively monitor for any changes.

Can you stop taking seizure medication because of side effects?

There is no doubt that medication side effects are unpleasant. However, you should not stop taking your medication unless told to by your doctor. There is a high risk of breakthrough seizures when you stop taking AEDs.

Learn more: What is drug resistant epilepsy?

What can your doctor do about seizure medication side effects?

If you notice you’re having anti-seizure medication side effects, your doctor might try a range of strategies:

• Reducing dosage: Sometimes side effects happen because there is simply too much of the AED in your system – reducing the dosage can help.
• Stopping polytherapy: Polytherapy is when you take more than one kind of anti-seizure medication (as well as other medicines). Going on to monotherapy (where you just take one), can bring side effects under control.
• Changing rhythm: You might be experiencing side effects because you take your AEDs once per day. This causes a spike of the medicine in your bloodstream. Your doctor may suggest taking smaller doses spread over the course of the day.
• Trying a different drug: It may also be helpful to simply try a different AED. Newer generations of AED often have fewer side effects.

It can also be helpful to monitor your medication side effects so you can talk about them with your doctor. You can use the Epsy App to keep a log of this.. 

Managing epilepsy medication side effects

Although seizure medication side effects can be very unpleasant, they do often pass on their own as your body adjusts. Rather than stopping taking seizure medication, it’s always best to talk to your doctor about the side effects you’re experiencing. Working together, you can develop a plan to manage them.

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[BLOG POST] Epilepsy in Pregnancy – making sure women’s voices are heard

Children who are exposed to certain prescribed medications in the womb can be at risk of poorer physical or neuro development. Over the past decade, research funded by Epilepsy Research UK has led to changes in policy and clinical practice relating to the use of epilepsy medication during pregnancy, including sodium valproate. On the Research Blog this month, we look at epilepsy during pregnancy, the journey in recognising the risks associated with sodium valproate and how research into epilepsy can make pregnancy safer for both mother and baby.

After being diagnosed with epilepsy when she was seven, Faye was able to control her seizures with medication for most of her life. However, becoming pregnant in 2014 provoked her epilepsy and ended a seizure-free run of two years. She found there was little support available for women like her with epilepsy during pregnancy.

“I’d always considered myself quite clued up on my epilepsy… life had other ideas for me,” Faye says. “I realised I knew little of the journey I would take as a woman having a child, and that if I felt this way then so would many others.”

Faye began blogging to share her experience and was overwhelmed with the response she got from other women in the same situation. “I found myself in a position to be the support to women that I so badly needed when I was pregnant.”

Sodium valproate is an effective antiepileptic drug (AED) that can also be prescribed for bipolar disorder and migraines. From the early 1970s, valproate was widely used as a treatment for epilepsy. But by the mid-1980s, doctors started reporting cases of physical birth abnormalities in children born to mothers who took valproate during pregnancy. Further research showed that valproate was also linked to developmental delays and long-term learning difficulties in children.

In all, it’s estimated that using sodium valproate during pregnancy carries a 1 in 10 risk of a physical birth abnormalities and 4 in 10 risk of a developmental delay or autism. But it took until 2018 for the European Medicines Agency to ban the use of valproate in women of childbearing age unless they are on a pregnancy prevention plan.

Why did it take so long for the concerns about the effects of sodium valproate to be properly recognised? A 2020 investigation led by Baroness Julia Cumberlege aimed to find out. The Independent Medicines and Medical Devices Safety Review found that not enough credibility was given to the early reports of birth defects – in short, the voices of women with epilepsy and scientists were not being listened to.

Research funded by Epilepsy Research UK and carried out by Dr Rebecca Bromley provided key evidence that sodium valproate was harming unborn babies. Alongside the efforts of campaigners, this work provided the evidence needed to drive change.

On the Research Blog later this month, Rebecca will provide an update on what has happened since the Cumberlege Review. She will also talk about her Epilepsy Research UK-funded work investigating the impact of seizures during pregnancy on children later in life.

The Cumberlege Review provided a timely reminder that there is much more research needed to make pregnancy safer for both women with epilepsy and their unborn children. Kim Morley is a midwife and nurse who specialises in epilepsy. On the Research Blog later this month, Kim will share her journey in providing care to women with epilepsy, and how being a voice for these women has contributed to highlighting their specific needs as well as developing her involvement in research.

The central finding of the Cumberlege Review was that the voices of people affected should have been listened to, but were not. In spite of this, Dr Rebecca Bromley believes that patient-led campaigns combined with research evidence were crucial for driving the changes in the use of valproate.

“Without the campaigning from patient groups I am unsure as to whether we would have seen such significant regulatory intervention,” Rebecca says. “Having attended many regulatory review meetings, it was the patient campaigners, I believe, that brought the severity of the possible deficits to life; in a way the research evidence alone was failing to do.”

To keep the pressure on and the momentum going, the Valproate Stakeholders Network was formed in 2016. It includes representatives from the MHRA (the UK medicines regulator) and epilepsy charities, including Epilepsy Research UK, as well as healthcare professionals. But most importantly, the network also involves people affected by sodium valproate and epilepsy during pregnancy, including Faye.

Next week on the Research Blog, Faye shares her own experience of pregnancy and motherhood and her role as a patient representative. Faye is determined to ensure that the voices of pregnant women with epilepsy are not ignored again. “My passion is to give women a voice and then a choice, especially when it’s something as important and life-changing as becoming a Mum.”

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[ARTICLE] First‐line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid – Full Text

Abstract

Objective

This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first‐line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.

Methods

In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow‐up was 36 months.

Results

In total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%–38%] vs 50% [95% CI 45%–55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%–19%] vs 28% [95% CI 23%–32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%–18%] vs 15% [95% CI 11%–18%]; P = .636).

Significance

Our results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first‐line AED treatment in patients with glioma.

Key Points

• Levetiracetam had better efficacy compared to valproic acid.
• Levetiracetam and valproic acid had a similar level of toxicity.
• Levetiracetam and valproic acid had a similar overall survival.
• Seizure control was similar in low‐grade (grade 2) and high‐grade (grade 3 or 4) glioma patients.

1 INTRODUCTION

Gliomas are the most common malignant primary brain tumors and treatment options are multimodal.^1, 2 Seizures are a well‐recognized symptom in glioma patients and occur frequently, either as a presenting symptom or during the course of the disease.³ The incidence of seizures is higher in slow‐growing tumors.⁴ Preoperative seizure incidence in diffuse gliomas ranges from ~25% in World Health Organization (WHO) grade 4 glioblastoma isocitrate dehydrogenase (IDH)‐wildtype to ~75% in grade 2 diffuse astrocytoma IDH‐mutant and oligodendroglioma IDH‐mutant 1p/19q co‐deleted patients.⁴ Seizure control plays an important role in the clinical management of gliomas and standard‐of‐care involves treatment with an antiepileptic drug (AED) once a first seizure has occurred.⁵ Seizure control can also be achieved with anti‐tumor treatment, including surgical resection, radiotherapy, and chemotherapy.⁶ Potential drug interactions between AEDs and chemotherapeutic drugs complicate seizure management in patients with glioma and therefore cytochrome P450 (CYP450) enzyme–inducing AEDs, such as phenytoin and carbamazepine, are generally not advised.² The choice of AED depends on physicians experience as the published literature lacks high‐quality comparative effectiveness studies. Currently, levetiracetam and valproic acid are two of the most commonly prescribed first‐line AEDs in patients with glioma.^6–9 Valproic acid is a first‐generation AED and has been used in the treatment of epilepsy for more than 50 years.¹⁰ It has a well‐established reputation as a broad spectrum AED and has been associated with decreased psychiatric and behavioral adverse effects in patients with epilepsy.^10, 11 As a CYP450 inhibitor, it has the potential to increase bioavailability of chemotherapeutic drugs and simultaneously increase toxicity of these drugs.¹² Valproic acid gained special attention approximately a decade ago, due to its supposed anti‐tumoral properties as a histone deacetylase inhibitor, especially in combination with temozolomide chemotherapy and radiotherapy.⁶ However, the results of a recent pooled analysis of prospective trials did not show improved survival outcomes in patients taking valproic acid.¹³ Levetiracetam is a second‐generation broad‐spectrum AED and was licensed ~20 years ago.¹⁴ It has several advantages, including a lack of hepatic metabolism and no known pharmacological interactions, and has a wider therapeutic index (the ratio between the median toxic dose and the median effective dose) than valproic acid.¹² Psychiatric and behavioral adverse effects are the most common adverse effects in patients using levetiracetam, frequently leading to discontinuation of the anticonvulsant.¹⁵ Other commonly prescribed AEDs in the glioma population include lamotrigine, lacosamide, topiramate, and zonisamide, each with their own efficacy and adverse‐effect profiles.^5, 9, 16

If more patients discontinue an AED due to inefficacy, intolerable adverse effects, or for alternative reasons, its usefulness decreases. The effectiveness of an AED is reflected in its treatment failure rates (or its inverse, retention rates), which encompasses both efficacy and tolerability of the treatment.¹⁷ Apart from seizure freedom, the retention rate is one of the recommended primary outcomes by the International League Against Epilepsy (ILAE).¹⁸ The effectiveness of levetiracetam compared with valproic acid has not been sufficiently investigated yet in patients with glioma. This retrospective observational study aimed to directly compare the effectiveness of first‐line monotherapy levetiracetam vs valproic acid.[…]

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[ARTICLE] Medication use in poststroke epilepsy: A descriptive study on switching of antiepileptic drug treatment – Full Text

Highlights

• It is unknown why patients switch their antiepileptic drugs in poststroke epilepsy.
• We found that 40% of patients needed to switch.
• 13% of patients switched because of ineffectivity of the first prescribed AED.
• Dosages at the time of switching were higher in case of ineffectivity than in case of side effects.

Abstract

Objective

Currently, as evidence-based guidelines are lacking, in patients with poststroke epilepsy (PSE), the choice of the first antiepileptic drug (AED) is left over to shared decision by the treating physician and patient. Although, it is not uncommon that patients with PSE subsequently switch their first prescribed AED to another AED, reasons for those switches are not reported yet. In the present study, we therefore assessed the reasons for switching the first prescribed AED in patients with PSE.

Method

We gathered a hospital-based case series of 53 adult patients with poststroke epilepsy and assessed the use of AEDs, comedication, and the reasons for switches between AEDs during treatment. We also determined the daily drug dose (DDD) at the switching moment.

Results

During a median follow-up of 62 months (Interquartile range [IQR] 69 months), 21 patients (40%) switched their first prescribed AED. Seven patients switched AED at least once because of ineffectivity only or a combination of ineffectivity and side effects, whereas 14 patients switched AED at least once because of side effects only. The DDD was significantly (p < 0.001) higher in case of medication switches due to ineffectivity (median 1.20, IQR 0.33) compared to switching due to side effects (median 0.67, IQR 0.07). There was no difference in the use of comedication between the group that switched because of ineffectivity compared to the group that switched because of side effects.

Conclusion

In our case series, up to 40% of patients with epilepsy after stroke needed to switch their first prescribed AED, mostly because of side effects in lower dosage ranges.

1. Introduction

Stroke is the cause of about 10% of all epilepsy and 55% of newly diagnosed seizures among the elderly [1]. Nevertheless, there are no specific evidence-based guidelines regarding treatment of patients with poststroke epilepsy (PSE). Therefore, the choice of antiepileptic drug (AED) is left over to shared decision by the treating physician and patient. From the 2013 International League Against Epilepsy (ILAE) report on initial monotherapy for epileptic seizures and syndromes, it appears that carbamazepine, levetiracetam, phenytoin, and zonisamide have ‘level A’ evidence for treating focal epilepsy in adults [2, 3, 4, 5]. This may already guide the choice of the AED by mainly effectivity arguments. On the other hand, according to a recent study by Larsson et al., in patients with PSE, retention rates are highest for levetiracetam and lamotrigine, and lowest for carbamazepine and phenytoin [6], meaning that carbamazepine and phenytoin are more often switched to another drug or discontinued. A 2018 review of randomized controlled trials on AED for the treatment of PSE found that levetiracetam and lamotrigine were better tolerated than carbamazepine [7]. However, reasons for discontinuation or switching of AEDs in patients with PSE are not reported. We therefore aimed to study the reasons for switching the first prescribed AED in patients with epilepsy after stroke.[…]

Continue —-> https://www.epilepsybehavior.com/article/S1525-5050(19)30593-1/fulltext

[ARTICLE] Prediction of the Recurrence Risk in Patients With Epilepsy After the Withdrawal of Antiepileptic Drugs – Full Text PDF

Abstract

Many seizure-free patients who consider withdrawing from antiepileptic drugs (AEDs) hope to discontinue treatment to avoid adverse effects. However, withdrawal has certain risks that are difficult to predict. In this study, we performed a literature review, summarized the causes of significant variability in the risk of postwithdrawal recurrent seizures, and reviewed study data on the age at onset, cause, types of seizures, epilepsy syndrome, magnetic resonance imaging (MRI) abnormalities, epilepsy surgery, and withdrawal outcomes of patients with epilepsy. Many factors are associated with recurrent seizures after AED withdrawal. For patients who are seizure-free after treatment, the role of an electroencephalogram (EEG) alone in ensuring safe withdrawal is limited. A series of prediction models for the postwithdrawal recurrence risk have incorporated various potentially important factors in a comprehensive analysis. We focused on the populations of studies investigating five risk prediction models and analyzed the predictive variables and recommended applications of each model, aiming to provide a reference for personalized withdrawal for patients with epilepsy in clinical practice.

Full Text PDF

[EDITORIAL] Reducing birth defects in women with epilepsy – Neurology

Merely 20 years ago, a report of the Quality Standards Subcommittee of the American Academy of Neurology recommended that antiepileptic drug (AED) selection for pregnant women with epilepsy should be based on the AED “deemed most appropriate for her seizure type.”¹ Scientifically, lumping all AEDs together when chemical structures and mechanisms of action differ greatly was questionable, but the evidence for differential effects on fetal outcomes was sparse. Multiple research studies have now made it clear that the level of risk for major congenital malformation (MCMs) differs substantially among AEDs. The prevalence of MCMs is highest with valproate monotherapy^2,3 compared to other monotherapies, and includes neural tube defects, heart malformations, cleft palate, hypospadias, and polydactyly. Likewise, the prevalence of MCMs is higher in polytherapy combinations that include valproate, compared to polytherapies that exclude valproate. MCM rates with some AED monotherapies even approximate the rates in the general population (e.g., levetiracetam, lamotrigine).^2,3

via Reducing birth defects in women with epilepsy | Neurology

[WEB SITE] What’s new and exciting in epilepsy research?

We asked Dr Robert Wykes, a translational medicine scientist for his personal perspective.  Here is his response:

Despite decades of new anti-epileptic drugs (AEDs) reaching market, the problem of drug refractory epilepsy remains. 25-30% of patients do not respond appropriately to AEDs. However in recent years advances in technology and non-pharmacological approaches are beginning to address this clinical need. We are beginning to see the translation of these therapies with exciting and promising results. I suspect within a decade, real progress will be made in treating or even curing the 25-30% who currently have few, often palliative options.

For some drug refractory patients surgery may be an option, but its success is dependent on precise localisation of a seizure onset zone. Improvements in neuroimaging and the electrophysiological devices used to detect seizure onset zones are increasing the accuracy of the area of the brain targeted for resection. There is also a realisation that many focal onset epilepsies may have a more distributed epileptic network. Mathematical modelling and application of advanced fMRI-EEG studies are identifying distributed epileptic networks. Further understanding of the importance of these networks may be key to improving surgical outcomes.

Surgery though is only an option for a minority of drug refractory patients. For those unsuitable for surgery promising and exciting results have been reported particularly in childhood epilepsies treated with cannabinoids (you can find out more about the ERUK position on medicinal cannabis here:) or components of the ketogenic diet such as decanoic acid. Further basic science investigations into the mechanism by which these compounds work may lead to molecules with improved anti-seizure properties. Antagomirs, molecules that block specific microRNAs upregulated in epileptic brain, have also shown considerable preclinical efficacy and are likely to enter clinical trials in the not too distant future.

Gene therapy holds promise, as this allows the ability to design strategies to achieve region-specific and cell-specific modification of neuronal and circuit excitability. The viral vectors that are used to deliver transgenes are increasingly reliable in terms of expressing the transgene, and data on long-term safety are accumulating from other neurological diseases. The potential to translate gene therapy research to human pharmacoresistant epilepsy is not straightforward. However a decade of preclinical proof or principle basic science has resulted in at least two gene therapy strategies currently being funded for first in human studies. It is envisioned that the first people to receive a gene therapy treatment for epilepsy could be within the next 18 months.

Recent advances in gene-editing technologies such as the CRISPR-Cas9 system could in the future result in entirely novel treatment for epilepsy by repairing disease-causing gene mutations. Although this technology offers the prospect of a ‘cure’ and can be applied to neurones in a petri dish, there are significant advances still required before this technology enters clinical translation for epilepsy.

I believe the biggest breakthrough will come however from basic science. It is astonishing to realize that we still don’t know how a seizure starts or how it stops! Recent advances that allow imaging of neuronal activity in awake rodents, coupled with the development of sophisticated multi-electrode devices and in combination with molecular techniques to target distinct types of neurons are shining a light on these fundamental questions. Further work in this area will result in a better understanding of seizure initiation and termination which may result in a radically different approach to treat people with epilepsy.

With many thanks to Dr Robert Wykes, University College London, Queen Square Institute of Neurology, for this contribution.

via What’s new and exciting in epilepsy research? | Epilepsy Research UK

[REVIEW] Summary of Antiepileptic Drugs Available in the United States of America – AMERICAN EPILEPSY SOCIETY

The current review summarizes the
main antiepileptic drugs available for
prescription in the United States as of
July 2018. One condensed, and one
expanded, table of the major properties
of 28 AEDs are presented both
to assist clinicians in providing care to
persons with epilepsy and to facilitate
the training of those in health care
educational programs.

This table is not intended to constitute
recommendations, only to provide an
easy reference listing of products on
the market.

Download Table (PDF)

[Abstract] The management of epilepsy in children and adults.

Abstract

The International League Against Epilepsy has recently published a new classification of epileptic seizures and epilepsies to reflect the major scientific advances in our understanding of the epilepsies since the last formal classification 28 years ago. The classification emphasises the importance of aetiology, which allows the optimisation of management. Antiepileptic drugs (AEDs) are the main approach to epilepsy treatment and achieve seizure freedom in about two-thirds of patients. More than 15 second generation AEDs have been introduced since the 1990s, expanding opportunities to tailor treatment for each patient. However, they have not substantially altered the overall seizure-free outcomes. Epilepsy surgery is the most effective treatment for drug-resistant focal epilepsy and should be considered as soon as appropriate trials of two AEDs have failed. The success of epilepsy surgery is influenced by different factors, including epilepsy syndrome, presence and type of epileptogenic lesion, and duration of post-operative follow-up. For patients who are not eligible for epilepsy surgery or for whom surgery has failed, trials of alternative AEDs or other non-pharmacological therapies, such as the ketogenic diet and neurostimulation, may improve seizure control. Ongoing research into novel antiepileptic agents, improved techniques to optimise epilepsy surgery, and other non-pharmacological therapies fuel hope to reduce the proportion of individuals with uncontrolled seizures. With the plethora of gene discoveries in the epilepsies, “precision therapies” specifically targeting the molecular underpinnings are beginning to emerge and hold great promise for future therapeutic approaches.

 

via The management of epilepsy in children and adults. – Abstract – Europe PMC