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Diagnostic utility of invasive EEG for epilepsy surgery: Indications, modalities, and techniques

Epilepsia - 6 hours 34 min ago
Summary

Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus-based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis on the application of various modalities in specific substrates or locations, taking into account their relative efficacy, safety, ease, and incremental cost-benefit. These recommendations aim to curtail outlying indications that risk the over- or underutilization of IEEG, while retaining substantial flexibility in keeping with most standard practices at epilepsy centers and addressing some of the needs of resource-poor regions around the world.

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Women with epilepsy initiating a progestin IUD: A prospective pilot study of safety and acceptability

Epilepsia - 6 hours 50 min ago
Summary Objective

Effective contraception enables women with epilepsy (WWE) to plan their pregnancies and improve outcomes for themselves and their children. Although popular among all women, complex drug interactions limit the efficacy and safety of oral contraceptives (OCs) for WWE. We sought to explore the safety, acceptability, and pharmacokinetic impact of a progestin-containing intrauterine device (IUD) in WWE.

Methods

We enrolled 20 women with well-controlled epilepsy and a stable antiepileptic drug (AED) regimen and who were initiating a progestin-containing IUD (levonorgestrel 52 mg) in a prospective, observational study. For each AED, we compared the trough concentration before IUD insertion to the trough concentration 3 weeks, and 3 and 6 months later. Participants recorded seizures in a daily paper diary. We compared seizures that occurred during the month before IUD insertion to those occurring in the 6 months thereafter. Participants completed an acceptability questionnaire at 3 and 6 months.

Results

Participants’ average age was 28 years; 60% were nulligravid. They reported a history of multiple seizure types. During the baseline month, 75% were seizure-free and the remainder reported between one and three seizures. Fourteen received monotherapy and six received polytherapy. Lamotrigine use was most common (n = 12). AED trough concentrations remained stable during the 6 months after IUD insertion, without clinically meaningful deviations from baseline. Diary data showed that seizure frequency worsened in 3, and remained unchanged in 13 and improved in 4 after IUD insertion. Subjectively, no participant believed the IUD worsened her seizure control. All participants were either somewhat or very satisfied with the IUD throughout the study. All participants continued the IUD use at 6 months. No pregnancies occurred.

Significance

This pilot study suggests that the progestin-containing IUD is a safe and acceptable long-acting contraceptive for WWE.

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Neuropsychological performance and seizure control after subsequent anteromesial temporal lobe resection following selective amygdalohippocampectomy

Epilepsia - 7 hours 4 min ago
Summary Objective

Selective amygdalohippocampectomy (sAHE) is a well-established treatment for temporal lobe epilepsy, commonly with favorable neuropsychological outcome. Yet, it is still unknown if subsequent resection of the anteromesial temporal lobe (AMTLR), when necessary, deteriorates neuropsychological performance in this selected group of patients. Thus, we evaluated the clinical and neuropsychological data of patients who, due to insufficient seizure control after sAHE, received a subsequent ipsilateral AMTLR and compared these findings with patients who did not receive a second resection (control group).

Methods

Patients’ characteristics and neuropsychological data were assessed and analyzed in the reoperated as well as in the control group at each step of treatment. Experienced neuropsychologists conducted the standardized examination focusing on verbal, figural and working memory, speech fluency and attention. Preoperative diagnostics included further continuous video-electroencephalography monitoring, high-resolution magnetic resonance imaging and functional transcranial Doppler sonography.

Results

Eighty patients having received sAHE in our center from 11/2007 to 02/2013 were included in this study. Seventeen of these patients underwent subsequent AMTLR. Thirteen of these were available for follow-up after the second surgery and twelve had a comprehensive neuropsychological testing at all three steps. Analyzing the neuropsychological data revealed no significant differences compared with controls. On the individual level, the data demonstrated that improvement in a subdomain was more frequent than decline, if the performance had already deteriorated after the first procedure. Seizure control improved significantly (p < 0.001) in all patients after subsequent AMTLR resulting in seven patients being seizure-free at follow-up.

Significance

Subsequent AMTLR following sAHE can be a safe procedure to improve seizure outcome in selected patients. In our series the risk for further neuropsychological deterioration after the second procedure was low. The neuropsychological performance after the sAHE can be a valuable criterion to advise patients who are eligible for a second surgery on their risk of further cognitive decline.

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Increasing the Levels of Certain Fats in the Brain Could Suppress Epileptic Seizures

Epilepsy Research - Tue, 09/27/2016 - 10:23

Increasing the levels of certain fat molecules in the brain could suppress epileptic seizures, according to a new ground-breaking study carried out by two collaborating groups in Belgium. The work is published in the leading scientific journal, Nature Structural & Molecular Biology.

The team focused their efforts on a protein called TBC1D24, since mutations in the gene that encodes it cause severe epilepsy. An almost identical protein called Skywalker exists in the fruit fly Drosophila melanogaster, an organism widely used to study different biological pathways and diseases.

The researchers had previously shown that Skywalker plays a vital role in maintaining communication between brain cells. In the current study, they successfully mapped the three dimensional structure of the Skywalker protein and found that it binds to specific fat molecules in the brain of the flies.

This led them to think that increasing the levels of these fats in the flies that have a faulty Skywalker gene may improve the effects of the fault. In fact, they found that the epileptic seizures completely disappeared in these flies.

In a press release, Prof Verstreken, a senior author on the study, said: “Our work shows that increasing specific brain fats at the synapses of patients with a TBC1D24 mutation is a possible strategy for preventing epileptic seizures. And although our work focuses on people with TBC1D24 mutations, we think that our findings could be relevant to various forms of epilepsy.”

Co-senior author, Professor Wim Versées, added: “Our two research groups will now continue to collaborate in order to seek out strategies for increasing the concentration of specific fats in the brain to prevent epileptic seizures. This research stems from cross-pollination between structural biology, biochemistry and genetics, so we will certainly continue down this interdisciplinary route.”

Author: Dr Özge Özkaya

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The 'worm' holds the key to treating epilepsy: New possibilities for rapid drug discovery

Medical News Today - Tue, 09/27/2016 - 08:00
Current methods to control epilepsy are not only inefficient but haven't improved in more than 150 years when the first anticonvulsant drug was developed.
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Scientists track down possible new treatment for epilepsy

Medical News Today - Tue, 09/27/2016 - 03:00
Increasing the concentration of specific fats in the brain could suppress epileptic seizures.
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The 'worm' holds the key to treating epilepsy

Science Daily - Mon, 09/26/2016 - 14:30
Current methods to control epilepsy are not only inefficient, but haven’t improved in more than 150 years when the first anticonvulsant drug was developed. Researchers have opened up the possibilities for rapid drug screens to treat seizures in the near future by developing the smallest whole-animal electroconvulsive seizure model using a microscopic nematode worm.
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Scientists track down possible new treatment for epilepsy

Science Daily - Mon, 09/26/2016 - 11:51
Increasing the concentration of specific fats in the brain could suppress epileptic seizures, ground-breaking new research shows. On the basis of this discovery, scientists were able to completely suppress epileptic seizures in fruit flies.
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The molecular and phenotypic spectrum of IQSEC2-related epilepsy

Epilepsia - Mon, 09/26/2016 - 02:32
Summary Objective

IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants.

Methods

Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians.

Results

Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic–clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut–like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features.

Significance

The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC2 should be evaluated in both male and female patients with an epileptic encephalopathy.

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HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption

Epilepsia - Mon, 09/26/2016 - 01:55
Summary Objective

Oxcarbazepine (OXC) is a widely used antiepileptic drug for the treatment of partial seizures that was developed through structural variation of carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions (cADRs) than carbamazepine, cADRs ranging from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis still limit the use of OXC in some patients. A few human leukocyte antigen (HLA)–related genetic risk factors for carbamazepine-induced cADRs have been identified. However, the HLA-related genetic risk factors associated with OXC-induced cADRs are unknown.

Methods

A total of 40 patients who experienced OXC-induced MPE and 70 patients who were tolerant to OXC treatment were included in the study. Genomic DNA was extracted from the peripheral blood of these patients, and high-resolution HLA genotyping was performed.

Results

The HLA-B*40:02 and HLA-DRB1*04:03 alleles were significantly associated with OXC-induced MPE compared with the OXC-tolerant group (odds ratio [OR] 4.33, p = 0.018 and OR 14.64, p = 0.003, respectively) and the general Korean population (OR 4.04, p = 0.001 and OR 3.11, p = 0.019, respectively). The HLA-B*15:01 genetic frequency was significantly lower in the OXC-MPE group compared to the OXC-tolerant group (OR 0.18, p = 0.016) and the Korean population (OR 0.22, p = 0.030). The allele frequencies of well-known HLA-related risk factors for carbamazepine-induced cADRs (HLA-B*15:02, A*31:01 and B*15:11) were not different among the three groups.

Significance

This study is the first to demonstrate an association of HLA-B*40:02 and HLA-DRB1*04:03 with OXC hypersensitivity using a large cohort of patients with OXC-induced MPE. These findings should be confirmed in future studies in different ethnic groups.

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Postoperative seizure control in patients with tumor-associated epilepsy

Epilepsia - Mon, 09/26/2016 - 01:35
Summary Objective

The patterns of postoperative seizure control and response to antiepileptic drugs (AEDs) in tumor-associated epilepsy (TAE) are poorly understood. We aim to document these characteristics in patients with supratentorial gliomas.

Methods

This was a retrospective analysis of 186 patients with supratentorial gliomas. Seizure patterns were classified into four groups: A, no postoperative seizure; B, early postoperative seizure control within 6 months; C, fluctuating seizure control; and D, never seizure-free. Rates and duration of seizure freedom, subsequent seizure relapse, and response to AED were analyzed.

Results

Among patients included, 49 (26.3%) had grade II, 28 (15.1%) had grade III, and 109 (58.6%) had grade IV glioma. Outcome pattern A was observed in 95 (51.1%), B in 22 (11.8%), C in 45 (24.2%), and D in 24 (12.9%). One hundred nineteen patients had at least one seizure and were classified as having TAE. Compared to pattern A, pattern B was predicted by histologic progression; pattern C by tumor grade, preoperative seizure, and histologic progression, and pattern D by preoperative seizure and gross total resection. Among patients with TAE, 57.5% of grade II, 68.2% of grade III, and 26.3% of grade IV experienced a period of 12-month seizure freedom. After first 12-month seizure remission, 39.1%, 60.0%, and 13.3% of grade II, III, and IV gliomas, respectively, experienced subsequent seizure; 22.6% of those with TAE reached terminal seizure freedom of at least 12 months on their first postoperative AED regimen, 6.5% on their second regimen, and 5.4% on subsequent regimens.

Significance

Distinct patterns of postoperative seizure control exist in gliomas; they have specific risk factor profiles, and we hypothesize these correspond to unique pathogenic mechanisms. Twelve-month seizure freedom with subsequent relapse is frequent in grade II–III gliomas. Response to AEDs is markedly poorer than with non-TAE, highlighting the complex epileptogenicity of gliomas.

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Temporal lobe epilepsy following maintenance electroconvulsive therapy—Electrical kindling in the human brain?

Epilepsia - Mon, 09/26/2016 - 01:15
Summary

Maintenance electroconvulsive therapy (ECT) is sometimes prescribed for refractory psychiatric conditions. We describe five patients who received maintenance ECT and developed florid temporal epileptiform abnormalities on electroencephalography (EEG) despite no history of epilepsy and normal neuroimaging. All patients had received regular ECT for at least 8 months. Three patients had clinical events consistent with epileptic seizures, and video-EEG monitoring captured electrographic seizures in two patients. After cessation of ECT the EEGs normalized in all patients, and no further clinical seizures occurred. Maintenance ECT may predispose to epilepsy with a seizure focus in the temporal lobe.

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Implementation of an established algorithm and modifications for the identification of epilepsy patients in the veterans health administration

Epilepsy Research Journal - Fri, 09/23/2016 - 00:00
Surveillance programs aimed at optimal care of patients and efficient resource management require accurate estimation of disease frequency measures (ILAE Commission Report, 1997; National Research Council, 2012; Thurman et al., 2011). Veterans Health Administration (VHA) is the largest among many managed healthcare organizations using lean data- driven processes for achieving best outcomes (Cosgrove et al., 2013). In alignment with this goal, VHA established the Epilepsy Centers of Excellence (ECoE) under Public Law S.
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New gene for severe childhood epilepsies

Epilepsy Research - Thu, 09/22/2016 - 07:53

A panel of international researchers has discovered that mutations in a gene called GRIN2D could cause severe epileptic encephalopathy.

GRIN2D is part of a gene family containing the information necessary to make proteins called NMDARs. These are ion channels found on the surface of nerve cells, and they play an important role in electrical signalling between them.

Mutations in NMDAR proteins are already known to cause childhood epilepsy by over-stimulating nerve signals and causing a toxic build-up of an important neurotransmitter called glutamate. However, until now, it was not known that GRIN2D could harbour disease-causing mutations.

The team, led by Dr Marni Falk, from the University of Pennsylvania and The Children’s Hospital of Philadelphia, reported a case of two unrelated children with epileptic encephalopathy in an article published in the American Journal of Human Genetics.

The researchers analysed the genes of both children and found a recurrent mutation in the GRIN2D gene in both. Conducting experiments on nerve cells grown in the laboratory, the scientists showed that this mutation causes NMDAR to remain open for too long, resulting in excess electrical signals that kill the neurons.

Based on this finding, the scientists gave the children a medicine called memantine, which blocks NMDAR and is already approved to treat people with Alzheimer’s disease. This led to a mild improvements and a modest reduction in their seizures.

However, one of the children began to deteriorate over time and had to be placed in an induced coma. Based on the results of previous animal studies, the researchers decided to treat the child with two other NMDAR blockers – magnesium and ketamine. Although neither drug is considered a standard treatment for epilepsy, they produced dramatic improvements, stopping the repeated non-convulsive seizures that the child was experiencing and allowed her to regain some developmental skills.

In a press release, Dr Falk said: “Much more work, including randomised clinical trials, remains to be done to learn whether therapies such as these, targeted to a specific gene disorder, can be applied to other patients with similar subtypes of epilepsy.”

This is a great example of how basic scientific research can be applied to develop treatments suitable to the unique genetic profile of a patient and reflect the potential of precision medicine.

Epileptic encephalopathy is a condition linked to neurodevelopmental disabilities and characterised by frequent seizures that cannot be controlled by common antiepileptic drugs.

Author: Dr Özge Özkaya

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Continuous Electrical Brain Stimulation Could be a Treatment Option for People with Drug-Resistant Epilepsy

Epilepsy Research - Thu, 09/22/2016 - 07:15

Continuous electrical brain stimulation could help to suppress epileptic seizures, offering a new treatment option for people who have epilepsy that cannot be treated with surgery or medication. These findings are published in JAMA Neurology,

First Author Dr Brian Lundstrom, at Mayo Clinic in Rochester, US, said: “We think this approach not only provides an effective treatment for those with focal epilepsy, but will allow us to develop ways of assessing seizure likelihood for all epilepsy patients. It would be of enormous clinical benefit if we could personalise treatment regimens for individual patients without waiting for seizures to happen.”

Doctors have attempted to suppress seizures by electrically stimulating the focus, or area in the brain where they originate. However, this approach rarely stopped seizures altogether.

In the present study, researchers found that electrical brain stimulation that couldn’t be felt by the patient was able to suppress electrical discharges that occur intermittently during normal brain function. It was also able to reduce the frequency and, in some cases, the intensity and duration of seizures.

Dr Lundstrom and colleagues conducted their study on 13 people with drug-resistant epilepsy who were also not eligible for surgery. They placed a grid of electrical contacts on their brains and sent stimulation at levels unnoticeable by the participants. In people for whom the electrical stimulation provided clinical benefits, the researchers replaced the temporary grid with a more permanent one that could offer continuous stimulation.

They found that 10 of the 13 patients (77%) reported improvement in both the severity of the epilepsy and their life satisfaction. The majority experienced more than a 50% reduction in seizures, and 44% were free of disabling seizures.

Epileptic seizures can be controlled with drugs in approximately two third of cases. However, one third of people with epilepsy have drug-resistant epilepsy. A proportion of these patients may be eligible for surgery where the focus, or portion of the brain in which seizures arise, is removed. Sometimes the focus is situated in an area of the brain that controls speech, language, vision, sensation or movement. In these cases surgery cannot be performed and electrical brain stimulation may be the only option.

Dr Lundstrom said that the risks associated with this approach are relatively minimal and include the risk of infection, bleeding and the stimulation being noticed by the patient.

According to the authors, further studies are needed to measure the exact effects of this treatment and examine the mechanism by which it suppresses seizures. They hope to examine the efficacy of this approach in more depth in the near future.

Author: Dr Özge Özkaya

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