Posts Tagged AED

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

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


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[NEWS] Surgery, precision medicine: the big hopes for epilepsy

19 March 2018

Αποτέλεσμα εικόνας για Surgery, precision medicine: the big hopes for epilepsy

PRECISION therapies targeting the molecular mechanisms of the disease are the shining hope for patients with uncontrolled, drug-resistant epilepsy, according to the authors of a narrative review published by the MJA.

The review was written in the wake of a new classification of epileptic seizures released by the International League Against Epilepsy (ILEA) in March 2017, which emphasises the importance of aetiology in allowing “optimisation of management”, as well as the importance of identifying comorbidities, such as learning, psychiatric and behavioural problems.

“The treatment of epilepsy relies primarily on antiepileptic drug (AED) therapy, which fully controls seizures in about two-thirds of patients,” wrote the authors – Dr Piero Perucca, consultant neurologist at the Royal Melbourne Hospital and Monash University, Professor Ingrid Scheffer, paediatric neurologist at Austin Health and the Florey Institute, and Dr Michelle Kiley, the director of Epilepsy Services at the Royal Adelaide Hospital.

“Second generation AEDs have expanded opportunities for tailoring treatment, but the burden of drug-resistant epilepsy, with its associated risks of disability, morbidity and mortality, has remained substantially unchanged for several decades.”

Over 15 second-generation AEDs have been developed since the 1990s and although they offer greater choice, and therefore more targeted options for patients, they have not significantly altered seizure-free outcomes.

Patients with drug-resistant epilepsy – defined by ILEA as “failure of adequate trials of two tolerated, appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure-freedom” – should be considered for surgery at the earliest opportunity, the review authors wrote.

“Epilepsy surgery involves resection or, less commonly, disconnection or destruction of epileptic tissue, and it is the most effective therapy for selected patients with drug-resistant epilepsy,” they wrote.

Despite that, and official recommendations from the American Academy of Neurology, the American Epilepsy Society and the American Association of Neurological Surgeons, delayed uptake of the surgical option remains “of concern”.

“These recommendations have not translated to increased use of epilepsy surgery,” Perucca and colleagues wrote.

“Consideration of epilepsy surgery still occurs typically 20 years after epilepsy onset, despite evidence of its effectiveness after failure of two adequate AED trials, and despite data suggesting that longer epilepsy duration adversely affects surgical outcome.”

Other non-pharmacological therapies – including vagus nerve stimulation, transcutaneous stimulation of the vagus or trigeminal nerve, deep brain stimulation of the anterior nucleus of the thalamus and responsive cortical stimulation, ketogenic diet and a modified Atkins diet – are also evaluated by the review authors as hopeful paths for research.

Perucca and colleagues were cautious in their hopes for medicinal cannabis.

“Scientifically sound evidence on the effectiveness of cannabinoids in epilepsy was provided only recently [in cases of Dravet and Lennox–Gastaut syndromes] … Overall, more evidence is required before cannabidiol can be considered further for the treatment of most individuals with epilepsy,” they wrote.

Precision medicine provides perhaps the brightest hope for patients battling resistant epilepsy, the review authors wrote.

“The advent of next-generation sequencing has fuelled renewed hope, especially following successful models developed in oncology.

“Epilepsy offers a promising opportunity for precision medicine, due to the myriad of gene discoveries, availability of experimental in vitro and in vivo models for drug screening, and the feasibility of conducting small, cost-effective trials of novel agents.

“For some genetic epilepsies, precision medicine is already a reality,” they said.

“A prime example is glucose transporter type 1 deficiency syndrome, in which dominant mutations in SLC2A1 result in impaired brain uptake of glucose. These patients respond to the ketogenic diet, which provides the brain with an alternative energy substrate.

“Identifying the molecular cause of epilepsy also allows the prevention or minimisation of AED adverse effects. In SCN1A-related epilepsies, sodium channel-blocking AEDs, such as carbamazepine, may aggravate seizures. In epilepsies due to POLG mutations, avoidance of valproate is recommended due to increased risk of hepatic failure.”

The review authors concluded by emphasising surgery and precision medicine as the areas of greatest potential for patients with epilepsy seeking to lead a seizure-free life.

“A subset of drug-resistant individuals can be rendered seizure-free by epilepsy surgery, which should be considered as soon as two AEDs have failed.

“In other individuals, seizure control can be improved by using alternative AEDs or non-pharmacological therapies, but they rarely result in seizure freedom.

“Hope to reduce the proportion of patients with uncontrolled seizures rests on future therapeutic advances, including precision therapies targeting underlying molecular mechanisms.”

via Surgery, precision medicine: the big hopes for epilepsy – MJA InSight 10, 19 March 2018 | doctorportal

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[WEB SITE] Serious Accidents Increased in Epilepsy

Mar 13, 2018
Take Home Points

Take Home Points

Epilepsy is associated with a 37% increased risk of serious traffic accidents. But taking antiepileptic drugs (AEDs) may not contribute to this risk, according to a new study published online in Neurology.1

The study is the largest so far to evaluate the risk of serious traffic accidents in epilepsy—and the first to evaluate all types of accidents, not just car crashes.

“We cannot determine to what extent the increased risk is seizure-related, but other studies have shown that the majority of car crashes in individuals with epilepsy are not caused by a seizure, although accidents in general seem to be,” wrote first author Helene Sundelin, PhD, of Linköping University Hospital (Linköping, Sweden), and colleagues.

Seizures impair awareness and motor skills, which can interfere with safe driving. While driving restrictions for people with epilepsy vary by country, many require AED treatment as a prerequisite before obtaining a license.
But the issue isn’t so straight forward. AEDs can also impair driving ability.  And, people with epilepsy may also suffer from psychiatric disorders and take psychiatric drugs, both of which may affect driving.

To tease out the contribution of these various factors to impaired driving in epilepsy, researchers conducted a study using Swedish national health registers. The study included 29,2220 adults with epilepsy but without cerebral palsy or intellectual disability, matched to 267,637 healthy controls. Researchers followed these individuals from 2006 to 2013 to see how many with epilepsy had serious traffic accidents requiring an ED visit or resulting in death and compared them to controls. Types of accidents included motor vehicular, motorcycle, bicycle, and pedestrian. Researchers also looked at whether the risk for accidents increased with AED use, as well as the impact of psychiatric comorbidities.

Key Results over 7 years for epilepsy vs controls:
• 1.27 times increased risk of serious traffic accidents
o Pedestrian: 2.2 times increased risk
o Bicycle: 1.7 times increased risk
o Motor vehicle: 1.3 increased risk
o Motorcycle: 1.2 times increased risk
• No significantly increased risk of serious traffic accidents with AEDs (HR 0.97; 95% CI 0.85–1.11)

Adjusting for psychiatric disorders and psychotropic medication did not change the results. This suggests that epilepsy is the main reason for increased risk of serious traffic accidents, according to the authors.
Further analysis showed that people with epilepsy have an estimated 297 more serious traffic accidents per year than controls. The numbers of serious pedestrian, bicycle, car and motorcycle accidents per year in epilepsy vs controls were also increased by 32, 133, and 28, respectively.

While AEDs were not linked to serious traffic accidents, only 25% of individuals in this study were actually taking them. These individuals may have been nonadherent, or no longer required AEDs. If they were in remission, they may have been at decreased risk of seizure and impaired driving. This limitation could explain why the study did not find a link between AEDs and serious traffic accidents. Further studies are needed to clarify this point.

Bottom line
The authors drew particular attention to bicycle and pedestrian accidents. Bicyclists are not required to have licenses, yet these accidents can be very serious and even deadly. People with epilepsy could benefit from increased awareness and education about prevention of these types of accidents, they stressed.

“Bicycle accidents in the general population are a growing problem as cycling becomes increasingly popular, which is probably true also for individuals with epilepsy. The increased risk of 70% should have implications both for implementations of safety measures and counseling of individuals with epilepsy. Our results raise the same concern for pedestrians with epilepsy,” they wrote. See: Take Home Points.


1. Sundelin HEK, Chang Z, Larsson H, et al. Epilepsy, antiepileptic drugs, and serious transport accidents: A nationwide cohort study. Neurology. 2018 Feb 28. pii: 10.1212/WNL.0000000000005210.


via Serious Accidents Increased in Epilepsy | Neurology Times

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[WEB SITE] Is epilepsy curable?

D&C-epilepsy cure-THS

Epilepsy is a medical disorder in which a person suffers from a tendency to throw repeated fits or seizures. Seizures occur because of sudden, uncontrolled electrical activity in the brain. It is amongst the most common neurological conditions. The causes of epilepsy can be many, which include brain infections, birth injury, tumours, trauma, congenital malformations, genetic and many others. There are many treatment options available that help to deal with the condition in a better manner and help one lead a fruitful life.

According to Dr Kaustubh Mahajan, Consultant Neurologist, Holy Family Hospital, Bandra, Mumbai, ‘Epilepsy is quite a serious problem in India. People should understand that it is a treatable disease.  In 30 percent of cases that we see is caused by infections in the brain like tuberculosis, which is completely curable and in another 60 percent cases the seizures can be completely controlled.’

As per the estimates, 1 out of every 100-200 person in India suffers from epilepsy, yet most of us have only a hazy idea of what it is. The major problem with epilepsy in our country is late detection. By the time the severity is gauged, the patient would have become an adult. Early detection is a must as it can lead to a complete cure.

Can people suffering from epilepsy prepare themselves to tackle a seizure or a fit?

‘Epileptic seizures often occur without a warning; however, some people may have an aura of the seizure before it occurs. The causes of epilepsy may vary from person to person. Seizures, anxiety, blank stares, headaches, sleepiness, staring spells, or temporary paralysis after a seizure is commonly seen in epilepsy,’ says Dr Kavita Barhate, Consultant Neurologist Dr Barhate’s Neurology clinic, Dombivali, Mumbai.A proper understanding of the causes and risk factor of epilepsy are essential for effective management of epilepsy in India, where the majority of patients are still untreated or inadequately treated.

Is epilepsy a life-threatening condition?

More than the condition it is the seizures that are dangerous. It can lead to accidents and other occupational hazards. It poses a huge risk, especially for those who work at high-rise buildings or near water which could lead to drowning.

What are the treatment options for epilepsy?

Here are few ways in which the condition can be treated:

Drug therapy: The first line of treatment that is offered is anti-epileptic drug or AED therapy. Drugs like phenytoin, oxcarbazepine, valproate, phenobarbitone and carbamazepine are conventional drugs are used. A combination of these drugs may be given if required. Complete withdrawal of drugs is considered only when the patient is seizure-free. Usually, the dosage of the drug is reduced gradually and over a period of 3–6 months (or longer) the patient may be free from seizures. In some cases, patients may need to be dependent on drug therapy for a lifetime.

Surgery: If a person doesn’t respond to drug therapy, then surgery is considered. Here are few ways in which the surgery is done:

  • Removal of seizure focus: It is the most common type of surgery where a small part of the brain where a disturbance in signals is observed is removed.
  • Multiple Subpial Transection: Sometimes, when the affected part cannot be removed, the surgeon may introduce series of incisions to prevent the signals from the affected part to reach other parts of the brain.
  • Lesionectomy: Epilepsy caused by the presence of a lesion can be treated by surgical removal of the legion.
  • Vagus nerve stimulation: This method is considered for people who are not fit for surgery. In this method, a device called vagus nerve stimulator is implanted under the skin of the patient in the chest. The device remains attached to the vagus nerve that delivers electrical signals to the brain thereby reducing seizures by 20 to 40 percent.

Image source: Shutterstock

Published: February 13, 2018 7:11 pm

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

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

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

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

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

General mechanism of action of the ketogenic diet

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

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


Direct inhibition of AMPA receptors by decanoic acid controls seizures

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

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

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

Inhibition of lactate dehydrogenase results in seizure suppression

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

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

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

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

Ketogenic diet modification of gut microbiota

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


Published: April 28, 2017



via Mechanisms of Ketogenic Diet Identify Novel Targets for AED Development

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[Abstract] Post-stroke epilepsy


Post-stroke epilepsy (PSE) is a major complication after stroke.

It is unclear which treatments are most effective in the prevention of recurrence of symptoms, or whether such therapy is needed for primary prevention.

The current understanding of epidemiology, diagnoses, mechanisms, risk factors, and treatments of PSE are covered in this review.


Post-stroke epilepsy (PSE) is a common complication after stroke, yet treatment options remain limited. While many physicians prescribe antiepileptic drugs (AED) for secondary prevention of PSE, it is unclear which treatments are most effective in the prevention of recurrence of symptoms, or whether such therapy is needed for primary prevention. This review discusses the current understanding of epidemiology, diagnoses, mechanisms, risk factors, and treatments of PSE.

Source: Post-stroke epilepsy

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[ARTICLE] Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy – Full Text


BACKGROUND: Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation do not achieve complete seizure freedom, and, therefore, previous studies of vagus nerve stimulation (VNS) therapy have focused instead on reduction of seizure frequency as a measure of treatment response.

OBJECTIVE: To elucidate rates and predictors of seizure freedom with VNS.

METHODS: We examined 5554 patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature including 2869 patients across 78 studies.

RESULTS: Registry data revealed a progressive increase over time in seizure freedom after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50% reduction seizure frequency), with 5.1% of patients becoming seizure-free, while 63% of patients were responders at 24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by age of epilepsy onset >12 years (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.38-2.58), and predominantly generalized seizure type (OR, 1.36; 95% CI, 1.01-1.82), while overall response to VNS was predicted by nonlesional epilepsy (OR, 1.38; 95% CI, 1.06-1.81). Systematic literature review results were consistent with the registry analysis: At 0 to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure-free, while at last follow-up, 60.1% of individuals were responders, with 8.0% achieving seizure freedom.

CONCLUSION: Response and seizure freedom rates increase over time with VNS therapy, although complete seizure freedom is achieved in a small percentage of patients.


Approximately 1% of the population has epilepsy, and seizures are refractory to antiepileptic drugs (AEDs) in approximately 30% of these individuals.1 Many patients with drug-resistant temporal or extratemporal lobe epilepsy can become seizure-free with surgical resection or ablation, but other patients with epilepsy are not candidates for resection given the presence of primary generalized seizures, nonlocalizable or multifocal seizure onset, or seizure onset from an eloquent brain region.2-5 Treatments based on neuromodulation, such as vagus nerve stimulation (VNS), have, therefore, become an increasingly important part of multimodal epilepsy treatment. VNS therapy was approved by the US Food and Drug Administration in 1997 as an adjunctive therapy for reducing seizures in patients with medically refractory epilepsy, and more than 80 000 patients have received treatment with VNS.6-8 The efficacy of VNS therapy has been evaluated by randomized controlled trials,9,10 retrospective case series,11,12 meta-analysis,13 and registry-based studies.14 These studies show that about 50% to 60% of patients achieve ≥50% reduction in seizure frequency after 2 years of treatment, and response rates increase over time, likely related to neuromodulatory effects with ongoing stimulation.13 Complete seizure freedom, however, is less common with VNS therapy and other neuromodulation treatment modalities.

Given that a minority of patients achieve seizure freedom with VNS, rates and predictors of seizure freedom have not been well studied and remain poorly understood. The vast majority of studies that evaluate VNS therapy focus on rate of response over time (defined as ≥50% reduction in seizures) and predictors of response; there has never been a large-scale evaluation of seizure freedom as a primary end point in patients treated with VNS. However, seizure freedom is the single best predictor of quality of life in patients with epilepsy,15,16 and therefore a better understanding of seizure freedom rates and predictors in patients treated with VNS therapy is critically needed. Importantly, this information may lead to improved patient selection and counseling in the treatment of drug-resistant epilepsy.

Here, we provide the first large-scale study of VNS therapy with a primary goal of defining seizure freedom rates and predictors, and comparing predictors of seizure freedom with those of overall response to treatment. Our study includes univariate and multivariate analyses of registry data including 5554 patients treated with VNS, and also includes a systematic review of the literature including 2869 patients across 78 studies, to help confirm registry-based results.

Continue —> Rates and Predictors of Seizure Freedom With Vagus Nerve Sti… : Neurosurgery

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[Abstract] The withdrawal of antiepileptic drugs in patients with low-grade and anaplastic glioma.


Introduction: The withdrawal of antiepileptic drugs (AEDs) in World Health Organization (WHO) grade II-III glioma patients with epilepsy is controversial, as the presence of a symptomatic lesion is often related to an increased risk of seizure relapse. However, some glioma patients may achieve long-term seizure freedom after antitumor treatment, raising questions about the necessity to continue AEDs, particularly when patients experience serious drug side effects.
Areas covered: In this review, we show the evidence in the literature from 1990-2016 for AED withdrawal in glioma patients. We put this issue into the context of risk factors for developing seizures in glioma, adverse effects of AEDs, seizure outcome after antitumor treatment, and outcome after AED withdrawal in patients with non-brain tumor related epilepsy.
Expert commentary: There is currently scarce evidence of the feasibility of AED withdrawal in glioma patients. AED withdrawal could be considered in patients with grade II-III glioma with a favorable prognosis, who have achieved stable disease and long-term seizure freedom. The potential benefits of AED withdrawal need to be carefully weighed against the presumed risk of seizure recurrence in a shared decision-making process by both the clinical physician and the patient.

Related articles

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Source: The withdrawal of antiepileptic drugs in patients with low-grade and anaplastic glioma – Expert Review of Neurotherapeutics –

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[WEB SITE] Seizure Decisions: After an unprovoked seizure, patients are often left wondering what’s next. A new guideline from a panel of epilepsy experts tries to answer that question.

Last September, Anthony Bonadio, 26, flew from New York to San Diego for a friend’s wedding. The morning after the wedding, he turned on the water for a shower—and the next thing he remembers is waking up in an ambulance. His friend, who was sharing the hotel room, says he heard a heavy thump followed by several more. He rushed to the bathroom and found Bonadio convulsing on the floor.

In October, after a long, stressful day playing piano in auditions for a Broadway musical, Nick Day, 23, went to bed and fell asleep. When he woke up, his girlfriend told him he’d had a seizure and an ambulance was on the way.

Both young men were examined by emergency department doctors, observed for a few hours, and sent home with orders to take it easy. Both were told that unprovoked seizures were quite common and that theirs may have been brought on by exhaustion.


Each year, an estimated 150,000 Americans experience unprovoked seizures—seizures without an obvious trigger like a blow to the head, a high fever, low blood sugar, or alcohol withdrawal. More than 50 percent of the time, patients will never have a second seizure, even though the cause of the first remains a mystery.

Neither Bonadio nor Day knew whether the seizure was an isolated incident or signaled the onset of epilepsy. Should they take antiepileptic drugs (AEDs) to reduce the risk of having a second seizure, or do nothing and hope they were among the percentage of patients who never have another seizure?

With such uncertainty common in medical practice, the American Academy of Neurology (AAN) and the American Epilepsy Society convened a panel of experts to review the available evidence and draft a guideline, published in the journal Neurology, to help patients and doctors decide what to do in the case of a first unprovoked seizure. The experts set out to answer three questions: If you have an unprovoked seizure, what is your risk of a second one? If you take an AED immediately after your first seizure, will this help you remain free of seizures in the long term? And are there any adverse side effects of AEDs that patients need to know about?


The panel found that the overall risk of experiencing a second seizure within five years of a first unprovoked seizure ranged from 21 to 46 percent in different studies. Significantly, the greatest risk was within the first two years, so if patients hadn’t had a seizure after two years their risk dropped substantially. The panel also found that certain clinical factors doubled the risk of a subsequent seizure: a preexisting lesion or injury to the brain; an electroencephalogram (EEG) showing abnormal spikes or electrical discharges, called epileptiform signals; a significant abnormality on a magnetic resonance imaging (MRI) scan; or a nocturnal seizure.“

Between 20 and 50 percent of patients will have another seizure. That means 50 to 80 percent will not,” says Gary S. Gronseth, MD, a co-author of the guideline, a professor of neurology at the University of Kansas School of Medicine, a Fellow of the AAN, and a member of the Neurology Now editorial advisory board. “So, the patient has to make a decision: ‘Should I take medication every single day to help reduce my risk of another seizure?’”


Day didn’t have to calculate his risk. He had a second seizure soon after the first, followed by four more. He was diagnosed with epilepsy and prescribed AEDs. He has been free of seizures since.

Bonadio, on the other hand, hasn’t had another seizure. However, his neurologist saw epileptiform signals on his first EEG, so Bonadio knows his risk of a second seizure and therefore of having epilepsy is higher than it would be for someone whose tests are normal. He’s still undecided about what to do.

Dr. Gronseth understands his dilemma. He suggests that patients crunch the numbers. “A good rule of thumb is that AEDs will reduce your risk of a seizure by half. So if your risk is 20 percent, drugs would make it 10 percent. If it’s 50 percent, taking AEDs would make it 25 percent.”


Another concern for Bonadio is the side effects of AEDs. Will they slow him down and make him less competitive in his high-stakes finance job?

Continue —>  Seizure Decisions: After an unprovoked seizure, patients are… : Neurology Now

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[ARTICLE] Epilepsy in patients with gliomas: Incidence and control of seizures


Brain tumor-related epilepsy (BTRE) is a unique condition that is distinct from primary epilepsy. The aim of this retrospective study was to clarify the epidemiology and results of treatment of BTRE in a single institution.

From a database of 121 consecutive patients with supratentorial gliomas treated at Chiba Cancer Center from 2006–2012, the incidence and control of seizures before and after surgery were retrospectively evaluated.Epilepsy occurred in 33.9% of patients before surgery. All patients received prophylactic anti-epileptic drugs (AED) during surgery; however, seizures occurred in 9.1% of patients within the first postoperative week.

During follow-up, seizures occurred in 48.3% of patients. The overall incidence of seizures was

  • 73.7% in patients with World Health Organization Grade II gliomas,
  • 66.7% in those with Grade III and
  • 56.8% in those with Grade IV gliomas.

Levetiracetam was very well tolerated. However, carbamazepine and phenytoin were poorly tolerated because of adverse effects. AED were discontinued in 56 patients. Fifteen of these patients (26.8%) had further seizures, half occurring within 3 months and 80% within 6 months of AED withdrawal. No clinical factors that indicated it was safe to discontinue AED were identified. The unpredictable epileptogenesis associated with gliomas and their excision requires prolonged administration of AED. To maintain quality of life and to safely and effectively control the tumor, it is necessary to select AED that do not adversely affect cognitive function or interact with other drugs, including anti-cancer agents.

via Epilepsy in patients with gliomas: Incidence and control of seizures.

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