Posts Tagged Epilepsy

[Abstract + References] Awareness and current knowledge of epilepsy


Epilepsy is a severe neural disorder that affects approximately fifty million individuals globally. Despite the fact that for most of the people with epilepsy, convulsions are better controlled by current accessible antiepileptic medicines, yet there are more than 30% of individuals affected with medically intractable epilepsy and around 30–40% of all patients with epilepsy affected by many adverse reactions and convulsion resistance to the present antiepileptic drugs. Consequently, various scientists attempt to develop new strategies to treat epilepsy, for instance, to find out novel antiepileptic ingredients from traditional medicines. This work aims to present a complete summary of natural medicines prescribed as antiepileptic agents all over the world by ethnic groups and different tribes. We undertook an extensive bibliographic analysis by searching peer reviewed papers and classical textbooks and further consulting well accepted worldwide scientific databases. We carried out PubMed, EMbase and CENTRAL searches by means of terms such as “antiepileptic” and “anti-convulsant” activity of plants. Medicinal plants have been prescribed to treat epilepsy and have been recognized as antiepileptic medicines. In this review, a variety of herbs have been reviewed for thorough studies such as Cuminum cyminum, Butea monosperma, Solanum americanum, Anacyclus pyrethrum, Leonotis leonurus, Elaeocarpus ganitrus and Angelica archangelica. This paper shows that it was high time experimental studies are increased to obtain novel potential active principles from medicinal plants. Plant extracts and their chemical constituents should be further evaluated to clarify their mechanisms of action. This paper provides a solid base upon which to further investigate the clinical efficacy of medicinal plants that are both currently prescribed by physicians as traditional antiepileptic agents, but also could be effective as an antiepileptic drug with further research and study.


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[ARTICLE] Εvaluation of machine learning methods for seizure prediction in epilepsy – Full Text PDF


Epilepsy affects about 50 million people worldwide of which one third is refractory to medication. An automated and reliable system that warns of impending seizures would greatly improve patient’s quality of life by overcoming the uncertainty and helplessness due to the unpredicted events. Here we present new seizure prediction results including a performance comparison of different methods. The analysis is based on a new set of intracranial EEG data that has been recorded in our working group during presurgical evaluation.
We applied two different methods for seizure prediction and evaluated their performance pseudoprospectively. The comparison of this evaluation with common statistical evaluation reveals possible reasons for overly optimistic estimations of the performance of seizure forecasting systems.

1 Introduction

Affecting about 1 % of the world population, epilepsy is one of the most common neurological diseases. Although seizures cover relatively short periods in a patient’s life, the uncertainty when the next seizure will occur can produce a high level of anxiety [4]. For 70 % of the patients, medication can reduce the frequency of seizures or even abolish them. However, patients report that unwanted side effects of the medication as well as the unpredictability of seizures are the severest handicaps of this disease [13]. A mobile system with the ability to predict seizures can help to relief the patients’ anxiety related to the uncertainty of events by enabling them to seek shelter, apply a short acting drug or inform the treating physician about the event. The device might also be used to prevent or mitigate the seizure [12].

Usually, seizure prediction is treated as a binary classification problem of brain activity, recorded as intracranial electroencephalography (icEEG) [8], with the state of impending seizures (preictal) being labeled as 1 and periods with a big temporal distance to the next seizure (interictal) labeled as 0. In this contribution, we present a new database that has been recorded in our working group. By intensifying the cooperation of clinical research and data analysis we minimize loss of descriptive metadata. For feature extraction and classification of the recorded icEEG signals we employed both, a recently proposed deep convolutional neural network and a featurebased method.


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[WEB PAGE] Identification and management of depression in people with epilepsy to save lives

Depression is the most common psychiatric comorbidity in people with epilepsy. Clinical studies have found that 20% to 30% of people with epilepsy have depression; the incidence may be as high as 50% to 55% in people visiting hospital epilepsy centers.

Untreated depression is associated with lower quality of life, poor treatment adherence, higher health care utilization and a risk for suicide up to 30 times higher than average.

Yet in most people with epilepsy, depression goes undetected. As an example, a Texas study conducted depression screening on 192 consecutive people visiting a high-volume epilepsy clinic. More than 1 in 4 people-;26%-;screened positive for depression and were subsequently diagnosed with depression. Of them, 65% had no previous history of the condition.

At the 33rd International Epilepsy Congress in Bangkok in June 2019, several sessions focused on psychiatric comorbidities in people with epilepsy and the crucial role of epileptologists in their identification and management.

Sometimes we think too much about the epileptology and not enough about comorbidities. There is individual clinician variation in this area. We must each recognize our own competency and know what we don’t know. Those are strongly influenced by our training, coworkers, culture, country and interests. But in the end, all clinicians must meet a minimum standard.”

Mike Kerr (UK), co-chair of a session on neuropsychiatric issues in epilepsy

This minimum standard was established by ILAE as part of its new epileptology curriculum. Domain 6 includes competencies and learning objectives about comorbidities, including the following:

6.1.1 Recognize psychiatric comorbidities, such as depression, anxiety, ADHD, psychosis and autism spectrum disorder

6.1.2 Appropriately manage or advise regarding psychiatric comorbidities

6.1.3 Adjust anti-seizure treatment as required by psychiatric comorbidities

However, the gap between knowledge and practice remains relatively wide. In a Bangkok session on psychological and psychiatric learning objectives in the ILAE curriculum, an informal survey found that most audience members did not conduct depression or suicidality screening in their clinics.

“Up to half of your patients will have depression and up to half will have anxiety,” said W. Curt LaFrance, Jr. (USA). “But almost no one in this session is using a depression screening tool.”

Generally, neurologists cite several reasons for not using screening tools or asking their patients about depression, including time constraints and the perception that screening is not their role. But physicians who manage the care of people with epilepsy are uniquely positioned to identify depression and initiate treatment that can improve quality of life and seizure control.

“It is part of our clinical responsibility as neurologists and epileptologists to take action in response to the high depression rates in people with epilepsy,” said Rosa Michaelis (Germany), co-chair of one of the sessions. “We should not expect other physicians to take over this task.”

Depression assessment: Individual variation

There’s no single “right” way for epileptologists to handle depression assessment and management, said Kerr. “Some people are multitaskers and will take on psychiatric management,” he said. “At the other end will be people who feel that none of it is their job. In the middle are the guiders, who keep epilepsy as a focus but also address the psychiatric issues.

Michaelis suggested that standardized screening is the most realistic strategy to increase detection rates. “We cannot rely on self-reported symptoms,” she said. Patients may not volunteer information about how they are feeling unless they are asked directly-;and even then, they may deny or downplay their symptoms, or physicians may misinterpret their complaints. Screening tools provide valuable information in only a few minutes; they also can be a gateway to conversations about depression and suicidality.

If the idea of establishing a formal screening program is overwhelming, Kerr suggested being alert to the possibility of depression in every patient and merely asking one question: “During the last month, have you felt down, depressed, or hopeless, or had little interest or pleasure in doing things?”

If the answer sounds at all like “Yes,” refer the patient to a mental health professional. Alternatively, he said, “If you feel competent in mental health assessment, consider using a validated measure” to get a better idea of the extent and severity of the patient’s issue.

For screening, Kerr and others in Bangkok recommended the Neurological Disorders and Depression Inventory in Epilepsy (NDDI-E), which is free for public use and available in more than a dozen languages. The NDDI-E consists of six short “feeling” statements:

  • Everything is a struggle
  • Nothing I do is right
  • Feel guilty
  • I’d be better off dead
  • Frustrated
  • Difficulty finding pleasure

For each statement, the person indicates how often they felt that way over the past two weeks. Points are given for each answer: always or often (4 points); sometimes (3); rarely (2); never (1).

A cutoff of 15 points is generally used to suggest depression, though cutoffs of 11 to 16 have been reported. According to Kerr, a cutoff score of 15 has 81% sensitivity and 90% specificity.

The Patient Health Questionnaire-9 (PHQ-9) or a shorter form, the PHQ-2, also can be administered.

The ILAE Commission on Psychiatry recommends annual screening, but many of the experts urged more frequent screening. They noted that because depression can be episodic, more frequent screening will better identify those patients in need of treatment. It also may improve patient-physician communication and trust.

Though the ILAE consensus statement does not include a recommendation for anxiety screening, Kerr urged clinicians to screen for anxiety as well. The NDDI-E screens for both depression and anxiety; Kerr also recommended the GAD-2 or the ET7, short questionnaires that have been tested in people with epilepsy. Patients with positive screens can be referred to a mental health specialist or assessed further.

“All clinicians should aim to identify depression and anxiety,” Kerr said. “To be a level-2 epileptologist by ILAE standards, you will have to know how to do this.”

Antidepressants: Myth and reality

Psychotherapy and medication are common treatments for depression. Though few studies have focused on the effectiveness of psychotherapy for depression specifically in people with epilepsy, dozens of trials and several meta-analyses support the use of cognitive behavioral therapy (CBT).

Some medical professionals may avoid prescribing antidepressants to people with epilepsy because they believe these drugs decrease the seizure threshold. There is little scientific basis for this, say experts.

A 2017 study followed adults with epilepsy six months before and after the initiation of antidepressant therapy with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norephinephrine reuptake inhibitors (SNRIs). Though the study was relatively small (N=84), the findings showed that antidepressants did not increase seizure frequency. In fact, among patients having more than one seizure per month at baseline, 27.5% went on to have less than 1 per month, and 48% had at least a 50% reduction in frequency. Of the patients, 73% had a therapeutic response to the antidepressant; changes in seizure frequency were independent of therapeutic response.

Pediatric screening

Janelle Wagner (USA) and Avani Modi (USA) addressed the issue of screening for depression and anxiety in the pediatric epilepsy population as it relates to two learning objectives in the ILAE curriculum:

  • 2.5.1 – Recognize when to refer patients for a higher level of care (as it relates to psychiatric comorbidities)
  • 2.9.1 – Provide counseling specific to children with epilepsy and their parents, according to the epilepsy types

Children with epilepsy are at higher risk than other children for depression, anxiety and attention deficit disorder, said Kette Valente (Brazil). Among children with epilepsy, 1 in 4 has depression, 1 in 4 has anxiety, and between 15% and 27% consider committing suicide.

A 2015 ILAE survey found that 55% of pediatric neurologists screened for these comorbidities, compared with only 7% in 2005. However, 50% of clinicians did not feel comfortable with their knowledge of anxiety, and only 40% said that screening for and managing comorbidities were priorities.

Depressive symptoms in children can look different than in adults, said Modi. Low self-esteem, cognitive symptoms, and negative thinking are common. Irritability and disruptive behavior also may be concerns, she said. “What may be seen as a conduct problem is actually depression.”

Valente, Wagner, and Modi described multiple screening instruments that take between 10 and 30 minutes to complete. Valente noted, however, that the instruments are often completed by parents, who do not always reflect their child’s behavior accurately.

The NDDI-E-Y, the pediatric version of the NDDI-E, had a sensitivity of 79% and a specificity of 92% in a 2016 validation study. Like the NDDI-E, the youth version can alert providers to suicidal ideation and provide a platform to discuss it.

Valente suggested screening children at their first visit, and then at certain time points:

  • Every 6 months
  • When seizures worsen
  • After medication changes
  • After any type of complaint about mood or behavior, whether it comes from the child or a parent or teacher

“Screening is not perfect, but it must be done,” she said. “There is no reason not to do it.”

Suicidality – what to do?

Jakob Christensen (Denmark) warned congress attendees that suicide risk overall is increasing worldwide, and that people with epilepsy have triple the risk of a suicide attempt and at least double the risk of death by suicide, compared with the general population. People with psychiatric comorbidities, and those recently diagnosed with epilepsy, are at even greater risk.

A recent meta-analysis found a prevalence of suicidal ideation of 23.2% among people with epilepsy-;more than 7 times the prevalence in the general population. The pooled event rate of completed suicide in the meta-analysis was 0.5%, more than 30 times higher than the global estimated suicide rate (0.016%).

Screening can reveal suicidal thoughts or plans; on the NDDI-E, this can be seen on item 4, “I’d be better off dead”. A score of 3 or 4 on this item has been shown to identify suicidality with 84% sensitivity and 91% specificity.

Christensen recommended asking every patient about suicidal thoughts. “It can be as simple as saying, ‘Do you ever feel like life isn’t worth living?’ he said. Asking the question will not increase the risk of suicidality, he said. “People who have these thoughts are actually quite happy to have you ask the question. They often don’t realize that suicidality can be associated with epilepsy.”

If NDDI-E results indicate suicidality, Milena Gandy (Australia) outlined next steps:

  • Ask the patient if they’ve thought about harming themselves in the past week. If they say yes, ask for details. Ask if they’ve ever tried to kill themselves and if so, how and when.
  • If you feel they may be in imminent danger of harming themselves, ask if they can guarantee their safety until you see them again.
  • If they ask for immediate help or can’t guarantee their safety, you can call a suicide hotline for them, refer them to the emergency room (or escort them there yourself), or refer them to a crisis service.
  • If they are not in immediate crisis, refer them for mental health support if they don’t already have it. If they do have it, talk with them about making an urgent appointment.

The clock is ticking

Screening and conversations do take time. And while all physicians are pressed for time, “We need to think creatively about how we can do what’s possible” with screening, said Markus Reuber (UK). For example, ensure that any patient information (brochures, videos, other handouts) includes mention of mood disorders and anxiety as common comorbidities.

Reuber also noted that some offices and centers have epilepsy nurses or community health advocates who can talk about mental health, and mental health services, with patients. Providers must find creative ways to make time for these issues, he said, as they are a crucial part of epilepsy treatment.

“We can draw on experiences from other health conditions,” said Modi. “In cancer care, chronic pain and heart disease, referring to a psychologist is common practice. Yet there are still some perceptions in neurological disorders that psychological care isn’t as important. But improving mental health can improve medical care.”


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[ARTICLE] Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience – Full Text

Until the early 1990s, a limited number of antiepileptic drugs (AEDs) were available. Since then, a large variety of new AEDs have been developed and introduced, several of them offering new modes of action. One of these new AED families is described and reviewed in this article. Levetiracetam (LEV) and brivaracetam (BRV) are pyrrolidone derivate compounds binding at the presynaptic SV2A receptor site and are thus representative of AEDs with a unique mode of action. LEV was extensively investigated in randomized controlled trials and has a very promising efficacy both in focal and generalized epilepsies. Its pharmacokinetic profile is favorable and LEV does not undergo clinically relevant interactions. Adverse reactions comprise mainly asthenia, somnolence, and behavioral symptoms. It has now been established as a first-line antiepileptic drug. BRV has been recently introduced as an adjunct antiepileptic drug in focal epilepsy with a similarly promising pharmacokinetic profile and possibly increased tolerability concerning psychiatric adverse events. This review summarizes the essential preclinical and clinical data of LEV and BRV that is currently available and includes the experiences at a large tertiary referral epilepsy center.

Since the introduction of bromides as the first effective antiepileptic drugs (AEDs),1 chronic AED treatment that consisted of the sustained prevention of epileptic seizures has remained the standard of epilepsy therapy.2 Before to the introduction of the newer generation of AEDs, a limited number of drugs were available that addressed the blockade of sodium channels, acting on gamma-aminobutyric acid (GABA) type A receptors, or interacting with calcium channels as the leading modes of action.3 With the introduction of the newer AEDs a heterogeneous group of drugs appeared, some of them offering new mechanisms of action2 including the blockade of GABA aminotransferase (vigabatrin [VGB]), GABA re-uptake from the synaptic cleft (tiagabine [TGB]), the modulation of calcium channels (gabapentin [GBP], pregabalin [PGB]), the selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolproprionic acid (AMPA) receptor antagonism (perampanel [PER]), and the binding to the presynaptic SV2A receptor site which is the unique mode of action of levetiracetam (LEV) and brivaracetam (BRV), the AEDs this review will cover. The authors will summarize the development of both compounds as derivatives of piracetam, review the currently available preclinical and clinical data, and discuss the question of whether BRV has the potential to be recognized as being superior to LEV and if it can replace it as the standard AED with the main mode of action both AEDs reflect.[…]


Continue —-> Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience – Bernhard J. Steinhoff, Anke M. Staack, 2019

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[Abstract] No prevention or cure of epilepsy as yet – Invited review


  • Approximately 20% of all epilepsy is caused by acute acquired injury such as traumatic brain injury, stroke and CNS infection, with potential to prevent epilepsy
  • No treatment to prevent acquired epilepsy exists; and very few clinical studies have been done during the last 15 years to develop such treatment
  • We review possible reasons for this, possible ways to rectify the situations and note some of the ways currently under way to do so
  • We further review “cures” of epilepsy that occur spontaneously, and after surgical and sometimes medical antiseizure treatments. We note the limited understanding of the mechanisms of such remissions and thus, at present inability to replicate them with targeted therapy


Approximately 20% of all epilepsy is caused by acute acquired injury such as traumatic brain injury, stroke and CNS infection. The known onset of the injury which triggers the epileptogenic process, early presentation to medical care, and a latency between the injury and the development of clinical epilepsy present an opportunity to intervene with treatment to prevent epilepsy. No such treatment exists and yet there has been remarkably little clinical research during the last 20 years to try to develop such treatment. We review possible reasons for this, possible ways to rectify the situations and note some of the ways currently under way to do so.

Resective surgical treatment can achieve “cure” in some patients but is sparsely utilized. In certain “self-limiting” syndromes of childhood and adolescence epilepsy remits spontaneously. In a proportion of patients who become seizure free on medications or with dietary treatment, seizure freedom persists when treatment is discontinued. We discuss these situations which can be considered “cures”; and note that at present we have little understanding of mechanism of such cures, and cannot therefore translate them into a treatment paradigm targeting a “cure” of epilepsy.

via No prevention or cure of epilepsy as yet – ScienceDirect

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[Abstract] Unintended pregnancy, prenatal care, newborn outcomes, and breastfeeding in women with epilepsy.


Objective To compare the proportions of unintended pregnancies, prenatal vitamin or folic acid (PNVF) use, adequate prenatal care visits, and breastfeeding among women with epilepsy (WWE) to women without epilepsy (WWoE).


Methods The Pregnancy Risk Assessment Monitoring System (PRAMS) is an annual survey of randomly sampled postpartum women administered by the Centers for Disease Control and Prevention. We used PRAMS data from 13 states from 2009 to 2014 to compare the primary outcomes in WWE and WWoE, as well as our secondary outcomes of contraception practices, newborn outcomes, and time to recognition of pregnancy. We adjusted for maternal age, race, ethnicity, and socioeconomic status (SES), and we calculated odds ratios for these outcomes using logistic regression.


Results This analysis included 73,619 women, of whom 541 (0.7%) reported epilepsy, representing 3,442,128 WWoE and 26,635 WWE through weighted sampling. In WWE, 55% of pregnancies were unintended compared to 48% in WWoE. After adjustment for covariates, epilepsy was not associated with unintended pregnancy or with inadequate prenatal care. WWE were less likely to report breastfeeding but more likely to report daily PNVF use. Newborns of WWE had higher rates of prematurity.


Conclusions Although planning for pregnancy is of utmost importance for WWE, more than half the pregnancies in WWE were unintended. Maternal age and SES differences likely contribute to the higher rates in WWE compared to WWoE. The proportion of women reporting breastfeeding is lower in WWE despite studies indicating the safety of breastfeeding in WWE.


via Unintended pregnancy, prenatal care, newborn outcomes, and breastfeeding in women with epilepsy | Neurology

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[BLOG POST] Mozart and epilepsy: the rhythm beats on


I can’t seem to get away from the theme of Mozart and epilepsy. When I first looked at this, in a blog post titled Mozart and seizures? The links between epilepsy and music, I took the topic rather lightly, more a subscript than a headline you may say. But I have since learnt to take the links between epilepsy and music more seriously.

By Barbara Krafft – The Bridgeman Art Library, Object 574471, Public Domain, Link


The major trigger for my ‘road to Damascus’ conversion is a 2018 paper titled Study of the Mozart effect in children with epileptic electroencephalograms, published in the journal Seizure. The paper was an eye-opener because it gave a very helpful comprehensive context to the broader beneficial effect of music…not just in epilepsy, but in other neurological disorders such as Parkinson’s diseasedementia and sleep disordersThe authors, Elyza Grylls and colleagues, started on the established premise that Mozart’s music has a beneficial effect on epilepsy. What they wanted to know was if other forms of music have a similar settling effect on epilepsy, or if only Mozart’s music carries the magic touch. The authors therefore played Mozart’s Sonata for two pianos in D major (K448) to 40 children with epilepsy who were undergoing an EEG (electroencephalogram, or electrical brain wave test). They then compared this with the effect of playing other types of music. Remarkably, they found that only Mozart’s Sonata led to a significant reduction in EEG epileptic discharges.

Public Domain, Link

The authors concluded that there was indeed an anti-epileptic effect of Mozart’s music, the so-called  ‘Mozart therapy’. But what is so special about K448? They speculate that it has to do with the structure of Mozart’s music, containing as it does, long periodicities. Interestingly, the music of Yanni, which is similarly structured, has somewhat a similar effect on brain wave activity. On the contrary, and sorry to Beethoven fans, Fur Elise doesn’t have this effect.

By W.J. Baker (held the expired copyright on the photograph) – Library of Congress[1]Contrairement à une erreur fréquemment répandue le buste a été réalisé par Hugo Hagen, non pas à partir du masque mortuaire mais, comme de nombreux autres, d’après le masque réalisé en 1812 par Franz Klein pour un buste qu’il devait réaliser ensuite., Public Domain, Link

So what does the structure of Mozart’s music do to the brain? One suggestion is that Mozart’s music enhances the body’s parasympathetic drive; this reduces the heart rate, and thereby inhibits the brain’s propensity to epileptic seizures. The suppression of this parasympathetic drive is of course the theory behind using vagus nerve stimulation (VNS) to treat drug-resistant epilepsy. For more on VNS, see my previous blog, Vagus nerve stimulation: from neurology and beyond!

By Bionerd – MRI at Charite Mitte, Berlin (used with permission), CC BY 3.0Link

You have surely wondered by now if K448 is the only one of Mozart’s compositions to have an anti-epileptic effect. It doesn’t matter if you have not, because the authors of another interesting paper did. They titled their study, published in 2018, Mozart’s music in children with drug-refractory epileptic encephalopathies: comparison of two protocols. Published in the journal Epilepsy and Behaviour, the authors, Giangennaro Coppola and colleagues, compared the effect of K448 with a set of his other compositions. Intriguingly they found that the composition set actually had a greater effect in epilepsy than K448…by a wide margin of 70% to 20%! Furthermore, the set was better tolerated by the children; they were less irritable and had a better nighttime sleep quality.

It therefore appears as if it all rosy in the garden of music and the brain. But it is not! As every rose grows on a thorny tree, so do some forms of music trigger epileptic seizures. This so-called musicogenic epilepsy is well-recognised, and two recent culprits are the music of Sean Paul, discussed in the journal Scientific American , and the music of Ne Yo, explored by NME. Therefore you should craft your playlist wisely.

By CLASSICNEYO – Own workCC BY-SA 4.0Link

So, is it time for neurologists to start prescribing music?

Or is it too much of a double-edged sword?

Music is #SimplyIrresistible. Luca Florio on Flickr.

via Mozart and epilepsy: the rhythm beats on – The Neurology Lounge

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[VIDEO] What’s, Why’s and How’s of the Vagus Nerve Stimulator

Dr Nemechek Discusses the Vagus Nerve Stimulator, how it’s used and what it can do for a patient.

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[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 monotherapy2,3 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

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[Abstract + References] Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy


Cannabidiol (CBD) is a major active component of the Cannabis plant, which, unlike tetrahydrocannabinol (THC), is devoid of euphoria-inducing properties. During the last 10 years, there has been increasing interest in the use of CBD-enriched products for the treatment of epilepsy. In 2018, an oil-based highly purified liquid formulation of CBD (Epidiolex) derived from Cannabis sativa was approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). The mechanisms underlying the antiseizure effects of CBD are unclear but may involve, among others, antagonism of G protein-coupled receptor 55 (GPR55), desensitization of transient receptor potential of vanilloid type 1 (TRPV1) channels, and inhibition of adenosine reuptake. CBD has complex and variable pharmacokinetics, with a prominent first-pass effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat/high-calorie meal. In four randomized, double-blind, parallel-group, adjunctive-therapy trials, CBD given at doses of 10 and 20 mg/kg/day administered in two divided administrations was found to be superior to placebo in reducing the frequency of drop seizures in patients with LGS and convulsive seizures in patients with DS. Preliminary results from a recently completed controlled trial indicate that efficacy also extends to the treatment of seizures associated with the tuberous sclerosis complex. The most common adverse events that differentiated CBD from placebo in controlled trials included somnolence/sedation, decreased appetite, increases in transaminases, and diarrhea, behavioral changes, skin rashes, fatigue, and sleep disturbances. About one-half of the patients included in the DS and LGS trials were receiving concomitant therapy with clobazam, and in these patients a CBD-induced increase in serum levels of the active metabolite norclobazam may have contributed to improved seizure outcomes and to precipitation of some adverse effects, particularly somnolence.


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