Full Seizure Research Articles

Stereotactic Electroencephalography in Patients with Drug-resistant Epilepsy

Stereotactic electroencephalography (SEEG) is an important method for invasive presurgical exploration of candidates for epilepsy surgery by means of stereotactic implantation of intracerebral electrodes without craniotomy. Implantations of intracerebral electrodes through craniotomy in drug-resistant epileptic patients have been performed in Bulgaria in the 1980s, but no further development of epilepsy surgery followed. The aim of our study is to present the first Bulgarian series of patients with drug-resistant epilepsy explored by SEEG. Our study included 53 patients with drug-resistant epilepsy explored by SEEG. Stereotactic Leksell frame, stereotactic software for avascular trajectory planning and depth electrodes with diameter of 0.8 mm and 8–18 contacts were used in all patients. Subsequently, long-term video-SEEG monitoring of various duration was performed and registered interictal and ictal EEG activity in order to evaluate the putative epileptogenic zone. Fifty-three patients were explored by 62 SEEGs because one patient underwent three SEEG procedures and seven patients – two SEEG procedures. We implanted 753 electrodes in these 62 SEEGs (mean: 12 electrodes per exploration; range: 5–20 electrodes). The mean age in our cohort was 23.6 years (4–60 years). The main indication for SEEG was MRI-negative epilepsy (20 patients). Focal cortical dysplasia was found in 17 cases, and hippocampal sclerosis in 8 cases. Surgical intervention was done in 48 patients (91%). Surgical resection of the epileptogenic zone (EZ) as defined by the SEEG was performed in 27 patients; radiofrequency stereotactic thermocoagulation (RFTC) on selected electrode contacts was applied in seven patients, and both procedures (i.e. RFTC followed by resective surgery) were performed on 14 patients. Full seizure control (Engel class I) was achieved in 28 patients (58.3%) and significant improvement – in 17 patients (35.4%). Three patients (6.2%) had no effect from surgery. No complications were observed in our series of 62 SEEGs. SEEG is a major tool for the determination of the EZ in patients with drug-resistant epilepsy who are candidates for epilepsy surgery, including MRI-negative cases or such without congruent data from the clinical, neurophysiological and neuroimaging perspectives. SEEG is a low-risk invasive diagnostic and even a therapeutic method when performed by experienced epilepsy surgery team.

Epileptic seizure control during and after pregnancy in Australian women.

To study factors that affected previous epileptic seizure control throughout pregnancy, during labour, and in the post-natal weeks. Analysis of data concerning seizure freedom that was available at various stages of 2337 pregnancies in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs, mainly employing multiple variable logistic regression techniques. Based on data available at the outset of pregnancy, the risk of seizure-affected that is, not seizure-free pregnancy was statistically significantly (p<.05) higher in pregnancies where there was previously uncontrolled epilepsy (78.1% vs. 20.8%) and focal epilepsy (51.3% vs. 39.7%), and decreased with later onset-age epilepsy (41.8% vs. 52.2% with onset before age 13years), The risk did not differ between initially antiseizure medication (ASM)-treated or untreated pregnancies. For epilepsy receiving ASM therapy, 90.6% of 160 pregnancies of women with uncontrolled focal epilepsy that began before the age of 13 were seizure-affected. None of the above factors influenced the risk of seizures during labour, though having seizures during pregnancy increased the hazard (3.93 vs. 0.6%). Either ASM-treated pregnancy or labour being seizure-affected increased the risk of post-partum period seizures (33.0% vs. 6.67% for both stages being seizure-free). Use of particular ASMs had no statistically significant effect on the seizure control situation at any of the pregnancy stages studied. Obtaining full seizure control before pregnancy appeared to be the main factor in maintaining seizure freedom during pregnancy, labour and the post-natal weeks.

Assessing efficacy and tolerability of lamotrigine (Sazar®) in therapy of female idiopathic generalized epilepsy: a multicenter study

Background. Idiopathic generalized epilepsy (IGE) comprises 15–20% among all types of epilepsy. However, specifics of administration for lamotrigine in IGE in the Russian Federation remain poorly investigated, especially in female subjects.Objective: to assess efficacy and potential adverse events (AEs) in girls and females with preserved childbearing potential and verified IGE upon initial treatment with lamotrigine, upon switching to lamotrigine from a first-antiepileptic drug (AED) that provided no full seizure control and/or was coupled to AEs, as well as while introducing lamotrigine as an adjunctive therapy in case a monotherapy achieved no therapeutic efficacy.Material and methods. There were enrolled 54 female patients aged 4 to 40 years (mean age 19.3 years, median 11 years). After verifying IGE, patients received a monotherapy with lamotrigine. In case a patient received a first monotherapy course, but achieved no full seizure control and/or was coupled to AEs due to administered AED, lamotrigine was prescribed as a second AED followed by a potential for further switch to a second monotherapy.Results. It was found that a first monotherapy resulted in the maximum remission rate in patients with isolated generalized tonic-clonic seizures. Lamotrigine efficiently suppressed EEG epiactivity, with observed EEG-remission in 8 out of 16 (50%) patients. While being administered as a second monotherapy, lamotrigine resulted in remission in 87.5% patients. A combination therapy with lamotrigine was required in 22 cases. Most commonly, it was combined with levetiracetam (15 patients). While administering a dual therapy with lamotrigine, remission was observed in 9 patients receiving basal therapy with this drug, as well as 3 and 1 patients receiving valproic acid and topiramate, respectively. Six more patients were observed to demonstrate more than 50% improvement (5 subjects in levetiracetam group and 1 in ethosuximide group).Conclusions. The study demonstrated high efficacy of administered lamotrigine as a first monotherapy as well as a second monotherapy and a combination therapy in girls, adolescent girls and females with IGE. Lamotrigine resulted in no serious AEs that might lead to its cancellation.

The control of treated generalized and focal epilepsies during pregnancy

ObjectivesTo examine factors contributing to failure to achieve full seizure control during pregnancy in women with anti-seizure medication (ASM) treated generalized epilepsy compared with focal epilepsy. ResultsFull seizure control was not attained in 51.4% of 1223 pregnancies of women with focal epilepsies in the Australian Pregnancy Register, and in 38.7% of 1026 pregnancies in women with generalized epilepsy (P < 0.05). For convulsive seizures only, the corresponding figures of 20.8% and 22.9% were reasonably similar. Where seizures had occurred in the pre-pregnancy year, 82.5% of the focal epilepsy pregnancies were seizure affected, and 70.1% of the generalized epilepsy ones (P < 0.05). Where the pre-pregnancy year was seizure free, the corresponding figures were 22.6% and 16.4% (P < 0.05), a roughly four-fold lower rate. Maternal age, epilepsy onset age, and epilepsy duration also differed between the focal and generalized epilepsy pregnancies. Multivariate regression analysis showed that generalized epilepsy and younger maternal age were associated with statistically significant decreased risks of seizure-affected pregnancy, and having seizure-affected pre-pregnancy years with an increased risk. However, for convulsive seizures only, the risk of seizure-affected pregnancy appeared increased in generalized epilepsy. ConclusionsThe risk of seizure-affected pregnancy appears lower in women with generalized epilepsy, independently of pre-pregnancy seizure control, itself a major determinant of the risk. The risk of having only convulsive seizures in pregnancy was not lower in generalized epilepsy than in focal epilepsy. ASM therapy seemed less effective in controlling focal than generalized epileptic seizures during pregnancy.

On the Fictitious Grease Lubrication Performance in a Four-Ball Tester

The extreme pressure (EP) behavior of grease is related to its additives that can prevent seizure. However, in this study following ASTM D2596 four-ball test method, the EP behavior of greases was modified without any changes to its additive package. A four-ball tester with position encoders and variable frequency drive system was used to control the speed ramp up time or delay in motor speed to demonstrate higher grease weld load and lower grease friction that were fictitious. A tenth of a second delay in speed ramp up time had showed an increase in the weld load from 7848 N to 9810 N for grease X and 6082 N to 9810 N for grease Y. Further increase in the speed ramp up time to 0.95 s showed that the greases passed the maximum load of 9810 N that was possible in the four-ball tester without seizure. The mechanism can be related to the delay in rise of local temperature to reach the melting point of steel required for full seizure or welding, that was theoretically attributed to an increase in heat loss as the speed ramp-up time was increased. Furthermore, the speed ramp up time increased the corrected load for grease X and Y. This resulted in lower friction for grease X and Y. This fictitious low friction can be attributed to decrease in surface roughness at higher extreme pressure or higher corrected load. This study suggests that speed ramp up time is a critical factor that should be further investigated by ASTM and grease manufacturers, to prevent the use of grease with fictitious EP behavior.

Experience with Low-Dose Sodium Valproate in Idiopathic Generalized Epilepsy Patients: A Long-Term Follow-Up Study on Selective Cohort from North India.

Background Idiopathic generalized epilepsy (IGE) is found in 20 to 30% of all patients presenting with seizures. Most of the patients require lifelong drug treatment. Efficacy and tolerability are important issues while selecting the most appropriate drug for a person with IGE. Objective The aim of this study was to look for usefulness of small dose valproate (<1,000 mg/day) in long-term treatment of IGE patients. Methods Diagnosis of IGE made with standard criteria among all patients presenting with seizures. Patients put on full doses of valproate (>1,000 mg/day) in first year, then reduction started in next year in patients with full seizure remission, and finally maintained on lowest possible dose of valproate. Lowest dose was defined as the minimum dose without seizures (between 200 and 900 mg/day). Patients, who were refractory on monotherapy, were put on add-on drug and followed for remission and reduction in doses of valproate at minimum possible dose. Results IGE was diagnosed in 21% of all patients presenting with seizures. Among 420 patients of IGE 368 (87.5%) were started on high-dose valproate monotherapy, 155 (42.1%) were responsive to single drug while 213 (57.9%) had been given add-on drug either lamotrigine or clonazepam or both. After minimum 3-year follow-up, 298 (81%) could be managed on low-dose valproate (<1,000 mg) without any relapse during 12 to 80 months follow-up. Conclusion Significant number of patients with IGE can be managed on low-dose valproate with good seizure control and less side effects.

Epilepsy Surgery: A Paediatric Perspective

Abstract 250,000 people in Australia live with Epilepsy and more than 40% of those are children. Medication is a first line, effective treatment. However, not all patients have the desired outcome of seizure reduction or cessation. In fact, 1 in 3 do not gain full seizure control with medication alone. Epilepsy surgery, while not a new concept of treatment for seizure management, has gained significant traction in the past decade and has become a particular focus of the Neurology Department at The Children’s Hospital, Westmead. This is evident by the expansion of the Neuroscience ward for the precise purpose of surgical intervention for the treatment of Epilepsy and other seizure conditions. The paediatric patient journey to surgery is a complex and intricate one. It involves a collaborative approach of the multidisciplinary teams from diagnosis and beyond, whilst maintaining a high standard of holistic, family centred care. This paper aims to discuss this journey and the impact it has on the patients, families and the nurses involved.

Evaluation of subchronic administration of antiseizure drugs in spontaneously seizing rats.

ObjectiveApproximately 30% of patients with epilepsy do not experience full seizure control on their antiseizure drug (ASD) regimen. Historically, screening for novel ASDs has relied on evaluating efficacy following a single administration of a test compound in either acute electrical or chemical seizure induction. However, the use of animal models of spontaneous seizures and repeated administration of test compounds may better differentiate novel compounds. Therefore, this approach has been instituted as part of the National Institute of Neurological Disorders and Stroke Epilepsy Therapy Screening Program screening paradigm for pharmacoresistant epilepsy.MethodsRats were treated with intraperitoneal kainic acid to induce status epilepticus and subsequent spontaneous recurrent seizures. After 12 weeks, rats were enrolled in drug screening studies. Using a 2‐week crossover design, selected ASDs were evaluated for their ability to protect against spontaneous seizures, using a video‐electroencephalographic monitoring system and automated seizure detection. Sixteen clinically available compounds were administered at maximally tolerated doses in this model. Dose intervals (1‐3 treatments/d) were selected based on known half‐lives for each compound.ResultsCarbamazepine (90 mg/kg/d), phenobarbital (30 mg/kg/d), and ezogabine (15 mg/kg/d) significantly reduced seizure burden at the doses evaluated. In addition, a dose‐response study of topiramate (20‐600 mg/kg/d) demonstrated that this compound reduced seizure burden at both therapeutic and supratherapeutic doses. However, none of the 16 ASDs conferred complete seizure freedom during the testing period at the doses tested.SignificanceDespite reductions in seizure burden, the lack of full seizure freedom for any ASD tested suggests that this screening paradigm may be useful for testing novel compounds with potential utility in pharmacoresistant epilepsy.

Tell Me How It Ends: The Path to Nationalizing the U.S. Pharmaceutical Industry

The U.S. medicines system is broken. Millions of Americans suffer and some even die because they cannot afford medicines discovered by government-funded research. At the same time, corporations holding monopoly patent rights to those medicines collect some of the largest profits in modern capitalist history. It does not have to be this way. The global legacy of treating essential medicines as a public good and the robust U.S. history of government seizure of private property for the public interest reveals a better path: the United States should nationalize its pharmaceutical industry. U.S. statutory law already provides broad powers for the executive branch to immediately order the substantial manufacturing and distribution of patent-free medicines. That statutory authority should be immediately implemented and further expanded. In addition, U.S. constitutional law justifies a full seizure of all industry assets. Given the pharmaceutical industry’s substantial reliance on government funding and licensing, along with the industry’s widespread malfeasance that harms the public welfare, the amount of compensation for this seizure will be limited. That seizure and compensation will finally conclude the tragic era of medicines profiteering and launch a new system that restores life-saving medications to their rightful role as affordable, accessible public goods.

Tell Me How It Ends: The Path to Nationalizing the U.S. Pharmaceutical Industry

The U.S. medicines system is broken. Millions of Americans suffer and some even die because they cannot afford medicines discovered by government-funded research. At the same time, corporations holding monopoly patent rights to those medicines collect some of the largest profits in modern capitalist history. It doesn’t have to be this way. The global legacy of treating essential medicines as a public good and the robust U.S. history of government seizure of private property when necessary for the public interest reveals a better path: the U.S. should nationalize its pharmaceutical industry. U.S. statutory law provides broad powers for the executive branch to immediately order patent-free medicines manufacturing and distribution. And U.S. constitutional law, interpreted in light of the pharmaceutical industry’s substantial reliance on government funding and licensing, along with the industry’s widespread malfeasance that harms the public welfare, justifies full seizure of all industry assets with limited compensation.

Assessment of Patients' Adherence to Antiepileptic Medications at Dessie Referral Hospital, Chronic Follow-Up, South Wollo, Amhara Region, North East Ethiopia.

An epileptic seizure is a clinical event presumed to result from an abnormal and excessive neuronal discharge. The clinical symptoms are paroxysmal and may include impaired consciousness and motor, sensory, autonomic, or psychic events perceived by the subject or an observer. Epilepsy occurs when 2 or more epileptic seizures occur unprovoked by any immediately identifiable cause. And in the majority of patients with epilepsy, antiepileptic drugs effectively control their illness. However, more than 30% of people with epilepsy do not attain full seizure control, even with the best available treatment regimen. The aim of this study is to assess self-reported adherence in adult patients with epilepsy and to identify potential barriers for nonadherence to antiepileptic drug treatment in Dessie Referral Hospital. A hospital based cross-sectional study was conducted using structured questionnaires including Morisky medication adherence scale and analysis was conducted descriptively using SPSS version 20. The level of nonadherence to antiepileptic medication regimens was 34.1%. The major reason for missing medication was forgetfulness 53.5%. And the most common side effect was sedation 56.2%. Conclusion. Majority of epileptic patients in Dessie Referral Hospital was adherent to their AEDs treatment and among the determinants of adherence assessed the level of education and the side effect of drugs showed statistical significance.

Electric fields fight deadly brain tumors [News

Jessica Morris was on a hiking trail in upstate New York last January when she suddenly uttered a line of gibberish and fell to the ground, her body shaking in a full seizure. A few hours later in a hospital she learned that she had glioblastoma, an aggressive brain tumor, and several days after that she was on the operating table having brain surgery. Since then, she's been fighting for her life.

Clozapine-induced myoclonus: a case report and review of the literature

We describe the case of a young man with treatment-resistant schizophrenia, who developed myoclonus during clozapine titration. This subsequently led to a full tonic-clonic seizure. Clozapine treatment can result in a range of seizure-like activity, the most well-known being tonic-clonic seizures. This case highlights the importance of recognizing and treating clozapine-induced myoclonus, as it can herald the onset of a full seizure, even at low serum clozapine levels. We highlight the variety of ways myoclonus can present clinically and suggest treatment options.

The natural history and prognosis of epilepsy.

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Generally, prognosis refers to the probability of attaining seizure freedom on treatment and little is known about the natural history of the untreated condition. Here, we summarize aspects of the prognosis and prognostic predictors of treated and untreated epilepsy and of its different syndromes. Usually, epilepsy is a fairly benign condition. Most epilepsies have a good prognosis for full seizure control and eventual discontinuation of AEDs, but epilepsy syndromes have differing outcomes and responses to treatment. Prognostic factors include aetiology, EEG abnormalities, type of seizures and the number of seizures experienced before treatment onset, and poor early effects of drugs. Early response to treatment is an important positive predictor of long-term prognosis, while the history of a high number of seizures at the time of diagnosis, intellectual disability, and symptomatic aetiology are negative predictors. Different prognostic patterns can be identified, suggesting that the epileptogenic process is not static. Epilepsy carries a greater than expected risk of premature death. Aetiology is the single most important risk factor for premature death.

Levetiracetam resistance: Synaptic signatures & corresponding promoter SNPs in epileptic hippocampi

Pharmacoresistance to antiepileptic drugs (AEDs) is a major clinical problem in patients with mesial temporal lobe epilepsy (mTLE). Levetiracetam (LEV) represents a unique type of AED as its high-affinity binding site, the synaptic vesicle protein SV2A, is a component of the presynaptic release machinery. LEV often leads to full seizure control even in previously refractory patients. However, approximately 30% of LEV-treated mTLE patients do not show a significant response to LEV from the beginning of the pharmacotherapy and are therefore classified as a priori non-responders. This unexpected phenomenon prompted genetic studies, which failed to characterize responsible SV2A sequence alterations.Here, we followed a different approach to study the mechanisms of LEV pharmacoresistance by screening for mRNA signatures specifically expressed in LEV a priori non-responders in epileptic brain tissue and subsequent promoter analyses of highly altered transcripts. To this end, we have used our unique access to analyze hippocampal tissue from pharmacoresistant TLE patients who underwent epilepsy surgery for seizure control (n=53) stratified according to a priori LEV responders versus patients with impaired LEV-response. Transcriptome (Illumina platform) and subsequent multimodal cluster analyses uncovered strikingly abundant synapse-associated molecule mRNA signatures in LEV a priori non-responders. Subsequent promoter characterization revealed accumulation of the single nucleotide polymorphism (SNP) rs9305614 G-allele in a priori non-responders to correlate to abundant mRNAs of phosphatidylinositol N-acetylglucosaminyltransferase (PIGP), i.e. a key component of the Wnt-signaling pathway. By luciferase assays, we observed significantly stronger activation by the LBP-1 transcription factor of the rs9305614 G-allele PIGP promoter. The present data suggest an abundance of transcripts encoding for key synaptic components in the hippocampi of LEV a priori non-responder mTLE patients, which for PIGP as proof of concept can be explained by a particular promoter variant. Our data argue for epigenetic factors predisposing for a priori LEV pharmacoresistance by transcriptional ‘overexposure of targets’.

Autism and Dietary Therapy

We report the history of a child with autism and epilepsy who, after limited response to other interventions following her regression into autism, was placed on a gluten-free, casein-free diet, after which she showed marked improvement in autistic and medical symptoms. Subsequently, following pubertal onset of seizures and after failing to achieve full seizure control pharmacologically she was advanced to a ketogenic diet that was customized to continue the gluten-free, casein-free regimen. On this diet, while still continuing on anticonvulsants, she showed significant improvement in seizure activity. This gluten-free casein-free ketogenic diet used medium-chain triglycerides rather than butter and cream as its primary source of fat. Medium-chain triglycerides are known to be highly ketogenic, and this allowed the use of a lower ratio (1.5:1) leaving more calories available for consumption of vegetables with their associated health benefits. Secondary benefits included resolution of morbid obesity and improvement of cognitive and behavioral features. Over the course of several years following her initial diagnosis, the child's Childhood Autism Rating Scale score decreased from 49 to 17, representing a change from severe autism to nonautistic, and her intelligence quotient increased 70 points. The initial electroencephalogram after seizure onset showed lengthy 3Hz spike-wave activity; 14 months after the initiation of the diet the child was essentially seizure free and the electroencephalogram showed only occasional 1-1.5 second spike-wave activity without clinical accompaniments.

Idiopathic Photosensitive Occipital Epilepsy

Idiopathic photosensitive occipital lobe epilepsy is a reflex, age- and localization-related syndrome. We describe the clinical and electroencephalographic features, therapy, and outcome of 16 children/adolescents with this syndrome. The cohort included 2 sets of siblings and 7 patients with other first- or second-degree relatives with a seizure history. All patients had occipital onset seizures and 15 had secondarily generalized tonic-clonic seizures. Seizure frequency was relatively low in all patients but one. Myoclonic seizures later developed in 2 patients with juvenile myoclonic epilepsy. Eight patients achieved full seizure control with monotherapy, and 5 required a second drug; 3 patients had rare seizures and were not treated with antiepileptics. Seven patients required special education or developmental assistance. This interesting syndrome sheds light on the pathophysiology and genetic etiology of common phenomena such as photosensitivity and headache. Further large prospective studies are required to better define this unique syndrome and its implications.

Is neurology ready to see the light?

Is neurology ready to see the light?

Clinical utility of adjunctive retigabine in partial onset seizures in adults

In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2–7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions – neuropathic pain, affective disorders, stroke, or even Alzheimer’s disease.

Spontaneously Resolving Seronegative Autoimmune Limbic Encephalitis

We describe a patient with seronegative autoimmune limbic encephalitis (SNALE) masquerading as glioma. Brain magnetic resonance imaging (MRI) abnormalities, distinctive pathological findings, and spontaneous remission are highlighted. There are 15 previously reported SNALE cases, 1 with pathology. A 66-year-old man presented with prominent amnestic syndrome, progressive cognitive decline, and refractory complex partial seizures. Initial brain MRI suggested herpes limbic encephalitis. A 3-week course of intravenous acyclovir was ineffective. Cerebrospinal fluid analysis revealed no pleocytosis. Repeat brain MRI showed a left uncal-hippocampal, contrast-enhancing lesion with mass effect, which was resected. Pathology revealed perivascular and parenchymal mixed lymphocytic inflammatory infiltrates, microglial nodules, neuronophagia, microglial activation, astrocytosis, and lymphocyte emperipolesis within neurons. Thorough searches for infectious pathogens and autoantibodies were negative. Six weeks later, a new enhancing right mesial temporal lesion appeared, with increased seizure activity and further cognitive impairment. Although immune therapy was declined, spontaneous resolution of the new enhancing lesion, with full seizure control and significant cognitive improvement, occurred. SNALE may masquerade as glioma. Pathologic changes in our case of SNALE are distinctive. Spontaneous resolution of a focal SNALE lesion may potentially occur without immune therapy.